Project Work – RUSBCHP601

REVIEW ON PSORIASIS AND MULTIPLE SCLEROSIS:

CERTAINITY AND UNCERTAINITY

Submitted by
DIVYA MARUTI DUDHAL
Roll No. B-7207
SAMRIN MOHAMMAD SAYED
Roll No. B-7233

Under the guidance of ADITI PATWARDHAN

Assistant Professor,
Department of Biochemistry
Ramnarain Ruia Autonomous College,
Matunga, Mumbai – 400 019.

Affiliated to University of Mumbai

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 Academic Year 2020-21

Certificate

This is to certify that Ms. SAMRIN MOHD SAYED.

student of T.Y.BSc. (Biochemistry) has completed Project Work titled

“REVIEW ON PSORIAISIS AND MULTIPLE SCLEROSIS: CERTAINIY AND

UNCERTAINITY” in accordance with the syllabus prescribed for Under-Graduate Degree
in Biochemistry at Ramnarain Ruia Autonomous College.

ADITI PATWARDHAN Mr. Prashant Masali.

Guiding Teacher Head, Department of Biochemistry

_________________

College Seal

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 INDEX

Page No Topic
5 Introduction

7 Etiology and Pathogenesis

11 Aim and objective

12 Multiple sclerosis and Psoriasis: links

15 a) Environmental Factor

16 b) Shared Genetic Factor

16 c) Shared cytokine profile

17 d) Demyelinating disorders associated with anti-TNF-alpha therapy

18 Multiple sclerosis and Psoriasis: is there an increased risk?

19 Studies suggesting positive correlation

22 Studies suggesting no correlation

24 Limitation of existing studies

25 Management and Treatment

30 Treatment of psoriasis in patients with concomitant multiple sclerosis

32 Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis

with Comorbid Conditions and Special Populations

32 Covid and Multiple sclerosis

47 Covid and Psoriasis

55 Areas of current and future research (e.g., IL-35)

57 Conclusion

58 Bibliography

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INTRODUCTION

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Psoriasis (PsO) has been associated with an increased risk of multiple comorbidities

including psoriatic arthritis (PsA), cardiovascular disease, diabetes mellitus, metabolic

syndrome, inflammatory bowel disease, and certain malignancies. Multiple sclerosis

(MS) has also been reported as a comorbidity in individuals with PsO, and vice versa.

This link between the two diseases may be somewhat unsurprising as both PsO and MS

are inflammatory disorders and exhibit similarities in genetic risk variants and

inflammatory pathways. Currently, limited and inconclusive evidence exists regarding

the relationship between the two conditions. This review explores the possible link

between PsO and MS and whether each condition serves as a potential risk factor for the

development of the other. The association of psoriasis (PsO) with other autoimmune and

autoinflammatory diseases has long been a topic of interest. Although previous studies

have attempted to clarify the specific relationship between PsO and multiple sclerosis

(MS), it remains obscure, with limited and conflicting evidence regarding a link between

the two entities. Herein, we review the etiology, pathogenesis, and treatment of each

disease and present the available literature to-date regarding a possible relationship

between PsO and MS. Previous studies have established strong evidence that Epstein-

Barr virus is related to multiple sclerosis, although few studies have investigated the

connection between Epstein-Barr virus and psoriasis. Investigators hypothesized that

Epstein-Barr virus might induce cutaneous manifestations, as herpes simplex virus does,

and these manifestations could result in the immunopathogenesis of psoriasis. MS

patients with concomitant autoimmune thyroid disease have peculiar HLA profile and

increased T cell-reactivity against specific antigens, compared to MS patients without

thyroid comorbidity, and show a prominent involvement of SC than other CNS locations,

that may be attributable to a cross-reactivity to similar thyroid and spinal antigens. MS

patients with comorbid psoriasis have a higher incidence of brainstem and cerebellar

attacks than those without psoriasis. Numerous researchers concluded that there is an

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increased prevalence of psoriasis between MS patients and their first-degree relatives,

although the opposite opinion also exists. In reports of coexistence of the two

autoimmune disorders, psoriasis most likely precedes MS, like in our case. In some

cases, a robust Th-17 immune response may be further amplified by Interferon-β

treatment for MS, leading to a psoriasis outburst or aggravation. Although the precise

pathway leading to the concurrence of psoriasis and multiple sclerosis remains unclear,

previous studies have focused on the immune system, environmental factors and

genomics. The association between the two diseases may stem from the shared immune

pathogenesis involving activation of T helper 1 (Th1) and Th17 cells, which lead to

production of pro-inflammatory cytokines. For multiple sclerosis, the proposed

immunopathogenesis involves interferon-Æ´ and TNF factors, along with IL-17, -21, -22

and -26, which are produced by Th17 cells. All of these cytokines are crucial in the

pathogenesis of psoriasis. Additionally, some reports state that vitamin D likely plays a

key role in psoriasis pathogenesis. Although the real mechanism remains unclear, and it

is tough to tell whether the relationship is direct or indirect, authors said, the shared

vitamin D deficiency may partly explain the possible association between psoriasis and

multiple sclerosis.

6
ETIOLOGY AND PATHOGENESIS:

PSORIASIS:

PsO is a T-cell mediated, systemic inflammatory disease that affects the skin and joints. It occurs in

approximately 2–4% of the US population with similar estimates in Europe. Although it can occur

at any age, PsO most commonly presents between the ages of 15 and 35 years with a second peak

occurring in the late 1950s to early 1960s.

It affects both men and women equally but preferentially affect persons of white

European ancestry.

PsO is characterized by an excessive and rapid growth of the epidermal skin layer.

Clinically, it typically presents as well-demarcated, erythematous plaques with overlying

silvery scale, most commonly on the extensor surfaces of the skin. An increased risk of

developing other chronic diseases also accompanies the diagnosis of PsO, some of which

include PsA, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular

disorders, anxiety, depression, Crohn’s disease, and lymphoma.

Approximately one-third of PsO patients will develop concomitant PsA . The

etiology of PsO is multifactorial with complex feedback loops and cross-talk

occurring between the innate and adaptive immune systems.

Contributing factors to the development of PsO include a genetic predisposition, a

proposed environmental or antigenic trigger, and dysregulation of the innate and adaptive

immune systems.

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 Native immune cells, including T-helper cells (T h1 and Th17), dendritic cells, and

keratinocytes, are thought to be activated by an initial antigenic stimulus, which results in

the production of pro-inflammatory cytokines.

Activated dendritic cells produce tumor necrosis factor (TNF)-alpha and IL-23, among

other cytokines. Antigen-presenting cells in the skin activate T-cells by secreting IL-12

and IL-23, leading to a cascade of various cytokines, which generates the chronic

inflammatory state of PsO.

This cascade of events, along with the TNF-alpha-governed pro-inflammatory

environment, leads to the development of cutaneous psoriatic plaques and augmented

inflammation which additionally contributes to the underlying comorbid conditions of

PsO.

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MULTIPLE SCLEROSIS:

MS is the most common demyelinating disease of the central nervous system (CNS). It affects

young adults, usually between the ages of 20 and 40 years, and has a strong female predominance.

It is defined by neurological symptoms that characteristically affect variable locations of the CNS

over periods of time.25 Typical presenting symptoms include visual disturbances, sensory

disturbances (such as paresthesias or hypoesthesia), motor weakness, cognitive deficits, fatigue, and

pain.

There is wide variation in the presentation of MS. Symptoms can range from mild,

benign symptoms to rapidly progressive, debilitating disease. MS has also been

associated with a decreased life expectancy by 7–14 years compared to the general,

healthy population.

The definitive pathogenesis of MS remains elusive, but, similar to PsO, it is thought to be

an immune-mediated inflammatory disorder, with both genetic and environmental

influences.

It is hypothesized that an as-of-yet unknown self-antigen, possibly a myelinassociated

antigen, is presented by antigen-presenting cells resulting in the production of

autoreactive T-helper cells (Th1 and Th17 cells) that then cross the blood–brain barrier

and release proinflammatory cytokines like IL-1, interferon (IFN)-gamma, TNF-alpha,

and lymphotoxin, resulting in the early inflammation of MS. Furthermore, studies have

indicated that there is an absence of Treg cells in lesions of MS, which provide protection

against inflammatory processes, suggesting a loss of a T-cell suppression mechanism in

the CNS.

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This immune cell-mediated inflammatory environment leads to demyelination, gliosis,

macrophage activation, and neuroaxonal degeneration, ultimately resulting in the

pathologic plaques in MS, characterized by confluent areas of demyelinated white and

gray matter involving the spinal cord and brain.

As a result, the typical neurological symptoms seen in MS arise. Later lesions of MS are

dominated by infiltration of B cells into the CNS, which are then able to produce IgM

and IgG leading to oligoclonal bands that can be detected in the cerebrospinal fluid.

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AIM and OBECTIVE: To find out the links and risks between PSORIASIS AND MULTIPLE

SCLEROSIS. To understand if there is a true link or association between the two conditions.

11
MULTIPLE SCLEROSIS AND PSORIASIS: LINKS

The concomitance of PsO and MS may be related to shared genetic and environmental

causes leading to an overactive immune system, or may also be related to general

immune system dysregulation, for which each condition is characterized by individual

alterations.

A meta-analysis of 43,643 patients with multiple sclerosis shows that these patients have

an increased incidence and prevalence of psoriasis.

A meta-analysis of 43,643 patients with multiple sclerosis shows that these patients have

an increased incidence and prevalence of psoriasis.

The review highlights the challenges of managing multiple sclerosis in the context of its

comorbidities and complications, specifically psoriasis, according to lead author Ching-

Chi Chi, M.D., Chang Gung Memorial Hospital, Taiwan. "Medical specialists should be

aware of the risk of developing psoriasis in patients with multiple sclerosis. Because both

disorders are attributed to autoimmune mechanisms, we suggest that dermatology

specialists may need not only neurology, but also rheumatology consultations. Further

laboratory or imaging studies may be necessary for psoriatic patients in whom

neurological symptoms appear," Chi and colleagues wrote.

Although the precise pathway leading to the concurrence of psoriasis and multiple

sclerosis remains unclear, previous studies have focused on the immune system,

environmental factors and genomics. The association between the two diseases may stem

from the shared immune pathogenesis involving activation of T helper 1 (Th1) and Th17

cells, which lead to production of pro-inflammatory cytokines.

12
For multiple sclerosis, the proposed immunopathogenesis involves interferon-Æ´ and

TNF factors, along with IL-17, -21, -22 and -26, which are produced by Th17 cells. All

of these cytokines are crucial in the pathogenesis of psoriasis.

The gut microbiome has been implicated in the pathogenesis of both multiple sclerosis

and psoriasis, as have genetic polymorphisms in HLA-DRB1 and IL-12B. Both pathways

warrant additional exploration, the authors wrote.

Confirmed environmental triggers for multiple sclerosis include ultraviolet radiation

exposure, Epstein-Barr virus, cigarette smoke and vitamin deficiency, but no evidence

suggests that the foregoing environmental factors are also the predisposing factor for

psoriasis. However, wrote Chi et al., they are related to psoriasis pathogenesis to some

degree. "For instance, vitamin D deficiency can affect the proliferation of cells and

immune response regulation. This might explain the increasing prevalence of multiple

sclerosis with latitude."

Additionally, some reports state that vitamin D likely plays a key role in psoriasis

pathogenesis. Although the real mechanism remains unclear, and it is tough to tell

whether the relationship is direct or indirect, authors said, the shared vitamin D

deficiency may partly explain the possible association between psoriasis and multiple

sclerosis.

Previous studies have established strong evidence that Epstein-Barr virus is related to

multiple sclerosis, although few studies have investigated the connection between

Epstein-Barr virus and psoriasis. Investigators hypothesized that Epstein-Barr virus might

induce cutaneous manifestations, as herpes simplex virus does, and these manifestations

could result in the immunopathogenesis of psoriasis.

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Cigarette smoke contains numerous toxic chemicals that induce inflammatory responses.

"Smoking can produce free radicals and oxidative stress that damage the signal

transduction pathway related to pathogenesis of psoriasis." Meanwhile, nicotine spurs

production of proinflammatory cytokines such as IL-12 and TNF.

Meta-analysis of five case-control and four cross-sectional studies yielded a pooled odds

ratio of 1.29 for prevalent psoriasis in patients with multiple sclerosis. From two cohort

studies, investigators calculated that patients with multiple sclerosis had a pooled hazard

ratio of 1.92 for psoriasis.

Two previous reviews investigating the link between multiple sclerosis and psoriasis

showed inconsistent results. One, published in the July 2010 Journal of Cutaneous

Medicine and Surgery, included five case-control/cross-sectional studies and found no

increased psoriasis in patients with multiple sclerosis. A subsequent review pooled data

from case-control/cross-sectional and cohort studies and found that patients with multiple

sclerosis had a 1.31 OR for psoriasis. This publication appeared in the May 2013 Journal

of Neurology.

"By contrast," Chi et al. wrote, "we included more recent studies and separately analyzed

data further according to different types of study design, thus providing robust evidence

on the association of multiple sclerosis with psoriasis."

The fact that the meta-analysis included only two cohort studies made it difficult to

explore the causal relationship between multiple sclerosis and psoriasis. Likewise, a lack

of non-Caucasian studies may limit the generalizability of the study's findings. The

analysis also excluded psoriasis subtypes and the impact of age, gender and disease

severity.

Dermatologists in clinical practice may have to take pre-existing multiple sclerosis into

account when managing psoriasis. "Nowadays, the commonly used medications for

psoriasis include topical corticosteroids, keratolytic agents and immunomodulators." Few

14
studies examine the effects of drugs on the association between the two diseases, the

author wrote. "The hazard may therefore be underestimated. We recommend that

clinicians be aware of this possibility. Furthermore, patients with psoriasis and a family

history of multiple sclerosis should be referred to neurologists for multiple sclerosis

screening, and vice versa."

T-helper 17 cells are involved in the pathogenesis of both psoriasis and MS. Both

conditions have been associated with interleukin-23 receptor (IL23R) polymorphisms.

Studies have reported psoriasis in 0.41 to 7.7% of individuals with MS. A higher rate of

psoriasis compared to controls was noted in a few small MS cohorts, but the number of

cases was too small to draw any firm conclusions. In two studies, including a large

Canadian study of 5,031 patients with MS, there was no increased prevalence of psoriasis

in patients over the control population. Family members of individuals with MS do not

appear to be at increased risk for psoriasis in these studies. Psoriasis has developed

during treatment for MS, and MS has developed during treatment for psoriasis.

A) ENVIRONMENTAL FACTORS:

A variety of known and unknown environmental factors are also thought to play a role in both PsO

and MS. As both are believed to be multifactorial diseases, environmental triggers may play a large

role in genetically susceptible individuals. Increased UV radiation exposure, low vitamin D levels,

Ebstein-Barr virus infection, and smoking have all been associated with an increased risk of MS.

Various infections (e.g., Streptococcus, Staphylococcus aureus, Helicobacter pylori,

HIV, and fungal infections) and medications (e.g., lithium, NSAID, anti-malarials,

betablockers, and angiotensin-converting enzyme inhibitors), smoking, obesity, and

increased stress levels have all been associated with an increased risk of PsO.

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B) SHARED GENETIC FACTORS AND GENETIC PREDISPOSITIONS:

Th17 cells and IL-23 receptor (R) polymorphisms are both associated with MS and PsO, along with

a number of other autoimmune inflammatory conditions. Multiple studies regarding the association

of these polymorphisms and the development of PsO and MS have been conducted. While separate

polymorphisms of the receptor are related to each condition, the two diseases seem to have unique

associated polymorphisms.

C) SHARED CYTOKINE PROFILES:

Both MS and Pso are T-cell mediated inflammatory conditions involving similar cytokines. The

IL-23/IL-17 axis is central to the pathogenesis of both MS and PsO. IL23 plays a role in both PsO

and MS by reinforcing the Th17 population expansion, serving as a pro-inflammatory cytokine in

both diseases.

The inflammatory response in PsO is promoted by T h17 cells, and similarly, CNS

infiltration of Th17 cells with the production of IL-17 occurs in MS patients.

Additionally, TNF-alpha is a key cytokine in both diseases. As with IL-17, increased

levels of TNF-alpha are found in both PsO and MS plaques, underlining the central role

of these inflammatory mediators in both diseases.

IL-27 is an additional cytokine involved in both MS and PsO, although in contrasting

roles. IL-27 acts to promote the differentiation of Th1 cells and inhibit the differentiation

of Th17 cells. In MS, the levels of IL-27 are significantly lower when compared to

patients without MS, resulting in relative lack of inhibition of ssTh17 differentiation.

In contrast, patients with PsO have higher levels of IL-27 relative to healthy patients,

increasing the representation of the Th1 profile. This is thought to act to prevent the

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progression of inflammation in PsO. In the population of patients with comorbid MS and

PsO, there is evidence of slower progression of MS.

It is hypothesized that the higher expression of IL-27/T h1 seen in PsO that results in

decreased Th17 differentiation and cytokine expression is able to counterbalance the

effects of decreased IL-27 expression and increased Th17 profile seen with MS.

D) DEMYELINATING DISORDERS ASSOCIATED WITH ANTI-TNF-ALPHA

THERAPY:

Another link between MS and PsO is illustrated with the use of anti-TNF-alpha therapy. TNF-alpha

inhibitors are a well-known treatment option for PsO. However, a potential link between TNF-alpha

inhibitors and demyelinating disease has been suggested. Demyelinating diseases with possible

association to anti-TNF-alpha therapy include MS, optic neuritis, Guillain–Barre syndrome,

transverse myelitis, and other peripheral neuropathies.

The use of TNF-alpha inhibitors in PsO patients with a personal history of a

demyelinating disorder or with a first-degree relative with MS is not recommended.

However, one study has suggested that the number needed to treat in patients with PsO

and MS is at least an order of magnitude smaller than the number needed to harm across

all comparisons of anti-TNF-alpha therapies and first-degree relative relationships,

suggesting TNF-alpha-inhibitor therapy could remain a treatment option for these

patients after all other systemic treatment classes have been exhausted, in close

collaboration with neurology colleagues, and while weighing the risks and benefits with

the patient.

After all, based on prior studies, it is unclear whether TNF-alpha inhibitors cause MS in

patients who may be predisposed or rather unmask MS that would have presented at a

later date. Several theories regarding the argument both for and against a pathogenic

relationship between TNF-alpha inhibitors and demyelination have been proposed.

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MULTIPLE SCLEROSIS AND PSORIASIS: IS THERE AN INCREASED RISK?

Although an association between MS and PsO has not been clearly elucidated, studies

have attempted to determine if an association does exist and whether having either

disease places one at a higher risk of developing the comorbid disease. To date, findings

have been conflicting.

Comorbid multiple sclerosis and psoriasis: characteristics of discussed studies

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STUDIES SUGGESTING POSITIVE CORRELATION:

Cendrowski was the first to observe an increased prevalence of PsO in Polish MS

patients, reported in 1989. He reviewed medical records of 51 patients with clinically

probable MS as well as 33 controls, and reported a higher incidence of PsO in the MS

group (1 in 17 vs 1 in 33, respectively).

However, he later published a more robust series of three groups of MS patients (n=285),

including these aforementioned 51 patients, and determined that PsO showed no

convincing association with MS. A small case-control study reported an increased

prevalence of PsO in patients with MS as compared to controls (6 of 117 vs 7 of 222,

respectively).

First-degree relatives of MS patients were also noted to have an increased prevalence of

PsO.

In one large, single-center, retrospective, cross-sectional study, PsO (n=5097) and MS

(n=1829) patients were identified via medical record from 2001 to 2014. Twentysix

patients were found to have concomitant diagnoses of PsO and MS.

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Five of these patients were diagnosed with PsA, as well. An association between PsO

and MS was found to be significant after adjusting for confounding variables such as sex,

age, PsA, and prior exposure to TNF-alpha agents (OR=1.521; 95% CI 1.01–

2.29;P=0.04).

A Danish study examined the risk of new-onset MS in patients with mild (n=58,628) or

severe (n=9952) PsO using a nationwide registry and found significantly increased

incidence rates for MS in both mild and severe PsO compared to the reference

population, suggesting that PsO may confer a risk of MS which increases with PsO

disease severity. Incidence rates for MS per 10,000 person-years were 1.78 (95% CI for

the reference population, 1.74–1.82) and for mild PsO and severe PsO, were 3.22 (95%

CI, 2.57–4.04), and 4.55 (95% CI, 2.52–8.22), respectively.

When incidence rates were adjusted for age, gender, socioeconomic status, smoking,

medication, comorbidity, and UV phototherapy, an increased risk of MS was also seen

(incidence rate ratio [IRR]=1.84, 95% CI 1.46–2.30 in mild PsO; IRR=2.61, 95% CI

1.44– 4.74 in severe PsO). When analyses included adjustments for family history of MS,

prior TNF-inhibitor treatment, or diagnosis of PsA, similar results were also seen.

Another study investigated various chronic inflammatory diseases and their association

with MS by looking at 155 patients with MS and 200 controls from 1976 to 1986.

MS patients had a significantly increased prevalence of PsO as compared to controls

(OR=2.01, CI 0.73–5.83). This study also supported prior studies showing that families

of MS patients experience no different rates of occurrence for autoimmune diseases when

compared to control families.

In 2013, a meta-analysis of autoimmune disease in those with MS was performed. Eight

studies that analyzed the risk of PsO in the MS population as well as their families were

included. These studies found an overall increased risk for PsO in MS patients (OR=1.31,

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95% CI 1.09–1.57, P<0.0001). There was no significantly increased risk for PsO in their

first-degree relatives (OR=1.17, 95% CI 0.94–1.46, P=0.16). A retrospective case-control

study in Israel investigated the impact of PsO on the disease activity and progression of

MS. This study included 3456 patients with PsO and MS who had been followed in

excess of 5 years.

Cases were compared to a matched control cohort of patients with only an MS diagnosis.

This study found that 1.3% of MS patients had PsO as a comorbid diagnosis, and 78%

(35 of 45) of these patients had PsO precede their MS diagnosis. Patients with PsO onset

before their relapsing-remitting MS onset had later MS disease onset in life, slower

progression of MS disability compared to patients without concurrent PsO, and

significantly longer time to both second relapse and until significant neurological

disability.

One case-control study investigated whether patients with a diagnosis of MS had higher

rates of concomitant PsO. They found that 9 of the 214 MS patients and 1 of the 192

consecutive controls had comorbid PsO. Six of the 9 MS patients with PsO had been

diagnosed with PsO prior to their MS diagnosis.

Most recently, a systematic review and meta-analysis of observational studies performed

in 2018 reported increased OR and HR of PsO in MS patients (OR 1.29, 95% CI, 1.14–

1.45; HR 1.92, 95% CI 1.32–2.80).

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STUDIES SUGGESTING NO CORRELATION:

In contrast, there have been several studies to suggest no association between PsO and MS. For

example, a prospective study of patients diagnosed with MS in England did not detect an

association with PsO. In this study, comorbidities of 658 consecutive patients attending a large MS

specialty clinic in Nottingham were recorded during 2002–2003. There were 454 females and 204

males that participated (18–80 years old, median age=45) in the study. The prevalence of PsO in

MS patients compared to the general population did not differ significantly.

Similarly, one of the largest published multicenter studies evaluated autoimmune disease

risk in MS patients as well as their families, comparing rates of occurrence to their first-

degree relatives, as well as in their unrelated spouses. In this study, 5031 MS patients

along with 30,529 of their first-degree relatives and spouses (n=2707 spouses) were

analyzed. The frequency of PsO in MS patients was found to be no different than for

their spousal controls (5.8% of MS population vs 5.4% of controls, P=0.44). No

significant difference in genders or in first-degree relatives of MS patients compared to

controls was found.

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In 2015, a systematic review of published studies to estimate the incidence and

prevalence of comorbid autoimmune disease in MS was performed. This study also

assessed the quality of these reviewed studies, finding less than half of the available

studies to be of high quality. The prevalence of PsO in MS varied widely, ranging from

0.39% to 7.74% in previously published studies. The highest estimate was reported by

Midgard et al’s population-based study (7.7% in MS patients vs 4% in controls).

A population-based cohort study utilizing the Danish Health Registration system

compared MS patients to the general population, estimating the relative risk of other

autoimmune diseases in patients with MS and their first-degree relatives. They reported a

small, insignificant, increased risk of PsO in patients with MS and no increased incidence

in their first-degree relatives. Laroni et al also failed to show an increased prevalence of

PsO in patients with MS when compared to controls (0.41% vs 0.82%, respectively).

Similarly, a systematic review of the literature also did not find an increased prevalence

of PsO in patients with MS.

Finally, a comorbidity survey conducted by the National Psoriasis Foundation which

spanned from 2003 to 2011 did not show an increased incidence of MS in patients with

PsO.

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LIMITATIONS OF EXISTING STUDIES:

An inherent limitation of most studies regarding the relationship between PsO and MS is a small

sample size, and often, an observational or retrospective design. Large patient numbers and a

reduction in selection bias have been attained in some studies that use nationwide databases, but

these databases often introduce a lack of diversity and therefore, limit the ability to extrapolate

results to larger, more ethnically diverse populations.

A limitation of nationwide database use or electronic medical record systems is also a

reliance on correct coding, introducing the possibility of unverified or incorrect

diagnoses.

In studies that included patient-reported conditions or histories, the potential for

ascertainment or reporting bias is large. Some of the above studies also used prevalence

data available in the literature, without age and sex matching, instead of obtaining a

control population from the same or a similar environment.

Meta-analyses are limited by the quality of the studies included and the manner in which

the information was obtained or collected in those studies. Psoriasis patients may also

24
receive increased medical attention compared to patients without the disease which could

lead to earlier, more frequent diagnoses of comorbid MS.

MANAGEMENT AND TREATMENT:

PSORIASIS:

Most patients with mild-to-moderate PsO can be well controlled on topical medications (i.e.,

corticosteroids, vitamin D analogs, coal tar, calcineurin inhibitors, retinoids, anthralin) and/or

phototherapy. For moderate-to-severe disease, systemic agents and/or biologic agents are often

indicated. Oral systemic therapies for PsO include methotrexate (MTX), acitretin, cyclosporine

(CYA), and apremilast. Biological therapies approved for use in PsO include TNF-alpha inhibitors

(adalimumab, etanercept, certolizumab pegol, infliximab), an IL-12/23p40 inhibitor (ustekinumab),

inhibitors of IL-17A (secukinumab, ixekizumab) the IL-17 receptor inhibitor (brodalumab), and IL-

23p19 inhibitors (guselkumab, tildrakizumab). Psoriasis (PsO) is a common, systemic, chronic,

inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling.

PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and

malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients,

and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease

25
and treatment management. Because certain populations have demographic or clinical

characteristics that can affect the presentation of PsO and complicate treatment responses, these

patient populations are largely excluded from clinical trials; therefore, most clinical evidence for the

treatment of these patients is derived from case reports and series. Secukinumab, a fully human

monoclonal interleukin-17A antibody, has been shown in several clinical trials to be effective and

safe for the treatment of PsO; however, these studies offer only limited data on the use of

secukinumab in patients with chronic illnesses or in special populations. This review explores the

use of secukinumab for PsO in special populations, including pregnant women, children, elderly

people, patients with erythrodermic PsO, and those with chronic illnesses, including latent

tuberculosis, hepatitis B and C, HIV, multiple sclerosis, and malignancies.

Deucravacitinib (BMS-986165, Bristol Myers Squibb), an oral, selective Tyrosine kinase 2 (TYK2)

inhibitor, was evaluated in two recent phase 3 studies investigating the safety and efficacy of the

drug as treatment for psoriasis.1 April Armstrong, MD, MPH, associate dean of Clinical Research

at Keck School of Medicine at the University of Southern California, Los Angeles, California,

presented the results from these studies at the American Academy of Dermatology Virtual Meeting

Experience 2021 (AAD VMX).

The two phase 3 studies, POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751),

compared deucravacitinib to both placebo and apremilast (Otezla, Amgen).

“PSO-1 and PSO-2 were global, double-blinded, 52-week studies that were identical in design up to

Week 24,” said Armstrong. PSO-1 enrolled 666 patients while PSO-2 had 1,020 patients.

Patients in these studies who met Psoriasis Area and Severity Index (PASI), static Physician Global

Assessment (sPGA), and body surface area (BSA) standards for moderate to severe plaque psoriasis

were randomized using a 2:1:1 ratio into 3 possible treatment groups: 6 mg of deucravacitinib once

26
daily, placebo, or 30 mg of apremilast twice daily. Placebo patients were switched to

deucravacitinib at Week 16 in both studies. Also, apremilast patients that failed to reach PASI 50 in

the PSO-1 study or PASI 75 in the PSO-2 study were switched to deucravacitinib at Week 24.

“PSO-2 also included a randomized withdrawal phase at Week 24,” Armstrong explained. “The

results of which will be presented at a future date.”

The coprimary endpoints were PASI 75 or sPGA 0/1, defined as clear or almost clear responses,

versus placebo at Week 16. The baseline demographics were similar between the two studies and

typical for trails in moderate to severe plaque psoriasis according to Armstrong. PSO-1 included

sites in Asia while PSO-2 did not.

“Mean patient weight was slightly higher in PSO-2 compared to PSO-1, likely reflecting the

difference between geographic distribution of patients,” Armstrong summarized.

The coprimary endpoint of the studies was to demonstrate deucravacitinib’s efficacy compared to

placebo defined as a proportion of patients achieving PASI 75 and sPGA 0/1 at Week 16. Results

showed that by the 16-week mark, 58.7% of patients who received the deucravacitinib achieved a

PASI 75 response compared to 35.1% of apremilast, and 12.7% of placebo. This trend continued

through Week 24, showing 82.5% of patients in PSO-1 and 81.4% in PSO-2 achieved PASI 75 and

continued treatment though Week 52 maintaining the response.

For sPGA, 53.6% of deucravacitinib patients in PSO-1 achieved a 0/1 response at Week 16. This is

greater than 32.1% of apremilast and 7.2% of placebo patients.1 These results were consistent

through Week 24 and comparable to the PSO-2 trial.

27
More than 60% of patients had moderate to severe plaque psoriasis affecting the scalp at baseline.

The breakdown of patients who met scalp specific sPGA 0/1 responses by Week 16 in PSO-1 is as

follows: 70.8% of deucravacitinib patients versus 39.1% of apremilast and 17.4% of placebo. These

outcomes were similar to those observed in PSO-2.

“Improvements were seen in base in PSSD [Psoriasis Symptoms and Signs Diary] symptoms,

which include itching, pain, stinging, and skin tightness,” said Armstrong.

About 95% of patients also had Dermatology Life Quality Index (DLQI) scores of ≥2% at baseline.

Over 40% of deucravacitinib patients compared to 28.6% apremilast and 10.6% placebo achieved

DLQI 0/1 response at Week 16 in PSO-1.1 Deucravacitinib effectiveness was also greater than

apremilast through Week 24.

Placebo, deucravacitinib, and apremilast had a similar total number of adverse events (AEs) and

serious adverse events (SAEs). These numbers include both the PSO-1 and the PSO-2 trials.

Deucravacitinib had 2.4% of AEs that lead to discontinuation. This was less than 3.8% of placebo

and 5.2% of apremilast patients.

The most common AEs across treatment groups were nasopharyngitis, upper respiratory tract

infection, headache, diarrhea, and nausea. One death occurred in each one of the treatment groups,

but none were attributed to the study.

“Due to the randomizations at Week 16 and Week 24 from apremilast, the total exposure to

deucravacitinib is nearly 1,000 patient years, with less than 250 patient years for placebo and

apremilast,” said Armstrong. “The safety profile for Weeks 0 to 52 are similar to those observed

from Week 0 to 16 with no new safety findings.”

28
Deucravacitinib had a low incident rate of around 2% for patients who experienced folliculitis and

acne. It led 1 patient to discontinue use. The adjusted exposure incident rates (AEIRs) for AEs of

interest showed malignancies and serious infections had similar rates among each trial group. None

of the patients who had a serious infection on deucravacitinib discontinued the study.

There was a total of 4 arterial thrombotic events reported in the deucravacitinib group, 1 of which

was considered serious. There was 1 SAE adjusted as a venous thromboembolism (VTE) in Week

48. A patient was hospitalized with an aortic dissection that was complicated by a thrombus in the

palmary artery. After aortic repair, the patient recovered and restarted treatment with

deucravacitinib for the long-term study.

The study also looked at 4 laboratory parameters that can be affected within the first 4 months of

treatment. “No clinically meaningful trends were observed in total cholesterol, creatine

phosphokinase, neutrophils, or platelets with deucravacitinib at 16 weeks,” said Armstrong.

“Similar results were observed in 52 weeks in these and other parameters.”

In both studies, deucravacitinib demonstrated superiority compared to placebo and apremilast in

both coprimary endpoints at Week 16, while therapeutic effect maintained through Week 52. Also,

deucravacitinib had a consistent safety profile between both studies and was well tolerated.

“Based on these findings deucravacitinib has the potential to become an efficacious, well-tolerated

treatment of choice for patients with moderate to severe plaque psoriasis,” concluded Armstrong.

29
MULTIPLE SCLEROSIS:

Treatment of MS varies based on the type of MS being treated and treatment goals. Progressive

types of MS are more difficult to treat successfully compared to relapsing forms of MS. Disease-

modifying treatment options for relapsing-remitting forms of MS include IFN-beta, glatiramer

acetate, dimethyl fumarate, teriflunomide, fingolimod, natalizumab, or alemtuzumab. The treatment

of progressive types of MS, with evidence of active inflammation, relies primarily on

immunosuppressive therapies, which unfortunately have self-limiting side effects with chronic use.

Treatment options for secondary progressive MS in addition to the disease-modifying treatments,

although of modest or lacking efficacy, include intravenous (IV) glucocorticoids, IV

cyclophosphamide, and MTX. Options for primary progressive MS include ocrelizumab (the only

drug approved for this type of MS), along with IV glucocorticoids, MTX, cladribine, mitoxantrone,

and IVIg. More recently, the use of IL17 inhibitors, specifically secukinumab, has shown reduction

in the number of active brain lesions on magnetic resonance imaging (MRI) scans in patients with

relapsingremitting MS.

For primary-progressive MS, ocrelizumab (Ocrevus) is the only FDA-approved disease-modifying

therapy (DMT). Those who receive this treatment are slightly less likely to progress than those who

are untreated.

30
For relapsing-remitting MS, several disease-modifying therapies are available.

Much of the immune response associated with MS occurs in the early stages of the disease.

Aggressive treatment with these medications as early as possible can lower the relapse rate, slow

the formation of new lesions, and potentially reduce risk of brain atrophy and disability

accumulation.

Many of the disease-modifying therapies used to treat MS carry significant health risks. Selecting

the right therapy for you will depend on careful consideration of many factors, including duration

and severity of disease, effectiveness of previous MS treatments, other health issues, cost, and

child-bearing status. Treatment options for relapsing-remitting MS include injectable and oral

medications.

Treatment of psoriasis in patients with concomitant multiple sclerosis:

As seen above, MS and PsO exhibit overlapping treatments including the use of fumarates (used

mainly in Northern Europe), IFN-beta with MTX, and IL-17 inhibitors. MTX and CYA are both

indicated for the treatment of PsO, and both also improve MS symptoms and reduce relapse rates.

Dimethylfumarate works by downregulating Th1 and Th17 cells, which are upregulated in

PsO and MS. This reduces the production of proinflammatory cytokines, including, but

not limited to, IL-12, IL-17 and IL-23, which have been implicated in PsO and MS. In a

small study, the addition of MTX to IFN-beta for the treatment of MS showed

improvement of MS lesions. On the other hand, PsO outbreaks have been described with

IFN-beta treatment for MS.

Secukinumab, an IL-17 inhibitor, is approved for use in PsO and PsA, and appears to be

safe in patients with MS. As mentioned above, secukinumab causes significant reduction

in MRI lesion activity in MS patients as well. The shared polymorphisms of the IL-23

31
receptor gene associated with MS and PsO may explain the efficacy of fumarates in both

diseases, in addition to the successful use of IL-17A inhibitors in both conditions.

Ustekinumab is an IL-12/23p40 inhibitor approved for use in PsO and PsA.

During a Phase II clinical trial, ustekinumab did not improve or worsen relapsing

remitting MS, and there are no reports of worsening neurological disease with

ustekinumab, allowing ustekinumab to remain as a treatment option in concomitant MS

and PsO.

As mentioned above, there is a possible increase in MS exacerbations, and demyelinating

disorders in general, with patients on anti-TNF alpha therapies. Phototherapy is not only

efficacious in PsO treatment, but also benefits patients with MS, likely due to an increase

in vitamin D levels which are deficient in patients with higher risk of MS and increased

severity of disease.

Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis with

Comorbid Conditions and Special Populations:

The emergence of data from clinical trials of biologics, the approval of new biologics, and our

improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for

the treatment of moderate-to-severe psoriasis. Biologics currently approved for the treatment of

psoriasis include tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors, ustekinumab (an

IL-12/23 inhibitor), and IL-23 inhibitors. Data from clinical trials and studies of the safety and

efficacy of biologics provide essential information for the personalization of patient care. We

discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment

recommendations according to current evidence, and propose psoriasis treatment algorithms. Our

discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis,

congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer,
32
lymphoma, and latent tuberculosis. We make evidence-based treatment recommendations for

special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and

pregnant and breastfeeding patients with psoriasis. Ultimately, individualized recommendations that

consider patient preferences, disease severity, comorbid conditions, and additional risk factors

should be offered to patients and updated as new trial data emerges.

Characteristics of COVID-19 disease in multiple sclerosis patients:

We read the study in a recent issue of Multiple Sclerosis and Related Disorders with great interest.

They reported a cross-sectional study among multiple sclerosis (MS) patients to identify suspected

COVID-19 cases and the factors associated with it. They suggested that most MS patients have a

mild course of CVID-19 infection.

The novel coronavirus disease (COVID-19) is in the pandemic stage with significant concerns for

individuals with an underlying health-related condition. Multiple sclerosis (MS) patients on

immunosuppressive/immunomodulatory disease modifying therapies (DMT) are generally at

increased risk of infections raising concern related to different risk or outcome in case of infection

with COVID-19. It is still uncertain, however, whether immunosuppressive agents increase or

33
decrease the severity of COVID-19 infection in MS patients. So, we designed this study to assess

characteristics and outcome of COVID-19 disease in our MS patients.

Out of 743 contacted cases, 543 answered. The mean (standard deviation [SD]) age was 35.28

(8.11) years and 81.2% (n = 441) of patients were female. The median (interquartile range [IQR])

for EDSS score and disease duration were 0.0 (0.0, 2.0) and 7.0 (4.5, 10.0), respectively. Fifty-six

(10.3%) patients were on no disease modifying therapy, 296 (54.4%) interferon beta, 35 (6.5%)

glatiramer acetate, 55 (10.1%) fingolimod, 27 (5.1%) dimethyl fumarate, 20 (3.7%) teriflunomide,

42 (7.7%) rituximab, and 12 (2.2%) natalizumab. In terms of clinical course of the disease, 435

(80.1%) patients had relapsing-remitting (RR) course, 43 (7.9%) secondary-progressive, 12 (2.2%)

primary-progressive, and 53 (9.8%) clinically isolated syndrome.

Of 543 patients, 66 cases reported symptoms suspicious for COVID-19 infection including dyspnea

in 33, (50.0%), sore throat in 30 (50.0%) anosmia or dysgeusiain 25 (37.9%), cough in 20 (30.3%),

gastrointestinal symptoms in 19 (28.8%), and fever in 10 (16.7%). Twelve patients performed chest

computed tomography (CT) scan or were tested for COVID-19 (RT-PCR). COVID-19 disease was

diagnosed in 9 patients (7 patients based on typical chest CT findings and 2 based on upper

respiratory tract RT-PCR), 4 patients were on interferon beta, 2 on no DMT, and one patient on

each of the following: fingolimod, glatiramer acetate, and rituximab. Seven patients had a mild

course of infection, one patient (treated with fingolimod) had severe course, and one patient (treated

with rituximab) had a critical course resulting in patient demise.

Although limited by small number of subjects the study on effect of DMTs on the COVID-19

disease outcome in the survey appears to be consistent with previous studies. It seems that patients

on treatment with interferon beta or glatiramer acetate developed mild CIVID-19 without severe

respiratory and neurological complications. The effect of fingolimod on COVID-19 is complex.

Although fingolimod is currently being investigated as a potential treatment for COVID-19

infection, some case studies, as well as single case suggests a more severe COVID-19 infection in

34
fingolimod-treated MS. Some studies proposed that anti-CD20 monoclonal antibodies such as

ocrelizumab and rituximab may have protective role against COVID-19 disease. However, Safavi

et al. suggested that anti-CD20 monoclonal antibodies can increase the susceptibility of MS patients

to COVID-19 infection. In the study, one patient treated with rituximab developed severe COVID-

19 disease and succumbed to the infection.

The study has some limitations. The study design was not appropriate to assess the prevalence of

COVID-19 disease in MS patients. However, explaining this issues is not in the scope of this study.

There is the possibility that the asymptomatic patients or cases with mild disease-related symptoms

had COVID-19 infection, but they didn't visit a doctor or undergo additional assessment. On the

other hand, it is possible that some patients with severe or critical course of disease could not

respond to our attempts to contacts them. Therefore, the effect of specific DMTs on the severity of

COVID-19 should be interpreted cautiously. Notwithstanding these limitations, the study suggests

that most MS patients developed uncomplicated COVID-19 infection. Further work is needed to

understand the implications of specific DMTs on COVID-19 disease fully.

SARS-CoV-2 infection can produce neurological features. The most common are headache,

anosmia and dysgeusia but patients may also develop other central nervous system (CNS) injuries.

A patient affected by Covid-19 who initially consulted for decreased visual acuity. The MRI

showed inflammation in the right optic nerve and demyelinating lesions in the CNS. It was

speculated that an immune mechanism induced by SARS-CoV-2, which can activate lymphocytes

and an inflammatory response, plays a role in the clinical onset of the disease. This pathogen may

be associated with either the triggering or the exacerbation of inflammatory/demyelinating disease.

The management of patients with chronic neurological diseases who receive immunomodulatory or

immunosuppressive medications has become more challenging during the outbreak of the

coronavirus disease 2019 (COVID-19). Most patients with multiple sclerosis are on long-term

35
DMTs. They are concerned that their underlying illness or their medications may increase the risk

of infection with the novel coronavirus or experiencing more severe or fatal disease. In fact,

respiratory tract infections are generally more common in MS, and their incidence increases with

age, level of disability, and male sex. Influenza-related hospitalizations and mortality are also

significantly higher in patients with MS. Additionally, DMTs, depending on their mechanisms of

action, may increase the risk of infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly described member of

the coronaviridae family with a zoonotic origin. Although, there is a 79% nucleotide similarity

between SARS-CoV-2 and previously recognized SARS-Cov-1, the etiology of SARS outbreak in

2002–2003, SARS-CoV-2 has higher infectivity and transmissibility in human and can manifest as

severe pneumonia or life-threatening acute respiratory distress syndrome. Several lines of

investigation suggest that intense innate immune response and lack of enough adaptive immunity

may contribute to the pathogenesis of the disease, and the release of a large number of

inflammatory cytokines may result in poor prognosis. For these reasons, a variety of

immunomodulatory medications have been proposed as potential treatments for complications of

COVID-19 and are currently being tested in clinical trial. So far, there have been a few case reports

or case series reporting on the risk and course of COVID-19 in patients with MS. However, we still

do not know the association of demographic features, disability level, or various DMTs with the

risk of this infection.

On February 19, 2020, the first confirmed cases of COVID-19 were announced in Iran. During the

next few weeks, COVID-19 was reported in every major city, and the country turned into an

epicenter of the disease in the region with a total reported case of more than 70,000 and around

5,000 deaths.

The aim of the current study B-cell depleting therapies may affect susceptibility to acute respiratory

illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran was to

36
determine the incidence of the clinical presentations suggestive for COVID-19 infection among

patients with MS in Iran during the first few weeks of the epidemic and explore the association of

demographics, clinical characteristics, and use of -DMTs with the risk of developing COVID-19.

This is a cross-sectional study of patients with central nervous system demyelinating diseases

(mostly relapsing-remitting and progressive MS) who are managed by a neurologist in a tertiary

care center in Tehran (AA). The study was approved by the ethics committee at the Tehran

University of Medical Sciences, and the written consent requirement was waived.

A questionnaire was sent to 2000 patients through an online portal system. One thousand, two

hundred forty-five patients confirmed receiving the survey, and 712 completed and returned the

questionnaire from March 26 to April 3, 2020. The data elements included age, sex, type of MS,

MS disease duration, current DMT and the length of being on the current DMT, disability level

(patient-determined disease steps or PDDS: a PDDS of four and higher requires assistance with

walking), the level of compliance with "stay at home recommendations," recent contact with a

person with respiratory symptoms or a patient with COVID-19 diagnosis, whether they have

developed any of these symptoms after February 20, 2020: fever, cough, shortness of breath, sore

throat, sneezing and runny nose, nausea and vomiting, and diarrhea, whether and how they have

been diagnosed with COVID-19 by a healthcare professional and if so, their disposition (home,

hospital ward or an ICU). None of the survey responders reported PCR-confirmed diagnosis so that

we defined a COVID-19-suspect group as patients who had 1) fever and cough, or 2) fever, and

shortness of breath, or 3) fever or cough or shortness of breath, plus a chest computed tomographic

(CT) scan that was interpreted as compatible with COVID-19 by a healthcare professional.

A total of 712 patients participate in the study (responded to the questionnaire). 78.5% of patients

were female with a mean (SD) age of 35 (8) years. 79.1 % had relapsing-remitting, and 16.2% had

progressive MS (primary or secondary). MS disease duration was 7.7 +/- 7.7 years. 95.5% of the

37
respondents received one of the DMTs for MS as follow: rituximab 40%, fingolimod 16.3%,

interferons 15.6%, dimethyl fumarate (DMF) 13.5%, teriflunomide 2.2%, natalizumab 2.5%,

glatiramer acetate3.7% and ocrelizumab 1.7%. Most patients (82.6%) were treated with the current

DMT for more than three months. The baseline PDSS score was less than 4 in 90.3%.

Out of 712 patients, 34 (4.8%) fulfilled our criteria for the COVID-19-suspect group. Thirty

patients were qualified by their reported symptoms only (fever and cough or fever and shortness of

breath); two patients were diagnosed based on the presence of fever or cough or shortness of breath,

plus a compatible chest CT. Two patients had a compatible CT and defining symptoms (either fever

and cough or fever and shortness of breath). Twenty out of 34 patients did not seek medical

attention and improved by staying home. Fourteen patients presented to their physician due to their

symptoms. Twelve were recommended to stay home and monitor the symptoms. They all improved.

Two out of 14 patients got admitted to a hospital due to the severity of pulmonary symptoms and

shortness of breath; however, they did not require ICU care or intubation and were eventually

discharged from the hospital.

There was no statistically significant difference in age, sex, disease type, disease duration, and

adherence to the recommended social distancing measures between groups. The difference in the

proportion of patients on different DMT categories between the two groups did not reach statistical

significance (Fisher's exact test p-value=0.059): 62% of patients in the COVID-19-suspect group

were on a B-cell depleting antibody while only 41% patient in the rest of participants (the none-

COVID-19-suspect group) were on B-cell depleting medications. Patients treated with interferons

or DMF had a lower chance of being in the COVID-19-suspect group: the proportion of interferon-

treated and DMF-treated patients were 8.8% and 5.9% in the COVID-19-suspect group and 15.9%

and 13.9%, in the non-COVID-19-suspect group, respectively. 41.2% of patients in the COVID-19-

suspect group reported a recent contact with a person with a fever or cough or shortness of breath.

The proportion of patients in the non-COVID-19-suspect group who reported a recent sick contact

was only 9.9% (p-value<0.001).

38
In the multivariable Poisson regression model, MS disease duration, the DMT category, and the

report of contact with a person with respiratory symptoms were all independently associated with

the risk of being in the COVID-19-suspect group. A one-year increase in the MS disease duration

was associated with an 8% decrease in the risk of being in the COVID-19-suspect group (95%CI:

0.86, 0.99, p-value=0.017). Being on B-cell depleting antibodies (as compared to non-cell

depleting, non-cell trafficking inhibitor DMTs) was associated with a 2.6-fold increase in the risk of

being in the COVID-19-suspect group. (RR: 3.55, 95%CI: 1.45, 8.68, p-value=0.005). There was

no statistically significant difference between patients who were on cell trafficking inhibitors or on

no DMT and those who were in the "other DMTs" group. Recent contact with a person with fever,

cough or shortness of breath, was associated with a 6.2-fold increase in the risk of being in the

COVID-19-suspect group (RR: 7.23, 95%CI: 3.48, 15.02, p-value<0.001). The results of the

sensitivity analysis model were in line with the main model

In this cross-sectional study, it was showed that a proportion of patients with MS developed

symptoms suggestive for COVID-19 in the early days of the epidemic in Iran. Most of the

symptomatic patients had a mild course, and only two required hospitalization, with eventual

recovery.

About 5% of our respondents could be categorized as COVID-19 suspects. This study was not

designed to estimate the incidence of COVID-19 among patients with MS. Population-based studies

are needed to achieve that goal. However, based on these results and prior reports of increased

incidence of respiratory infections among patients with MS, it is probable that the incidence of

COVID-19 could be higher in this patient population. On the other hand, it is possible that patients

with MS and other chronic diseases may follow quarantine and social distancing guidelines more

stringently and, in the long term, experience a lower incidence of COVID-19 compared to the

general population.

39
Despite the observation of a relatively high proportion of COVID-19-suspect patients in the survey

respondents, the course of the disease did not seem to be more severe as compared to the general

population. The good outcome in MS patients contracted with COVID-19 is also supported by a

report of the Italian study group on COVID-19 in MS patients . The patients with MS in the study

were relatively young, and the observed favorable outcomes are consistent with the reported good

outcomes in young, otherwise healthy COVID-19 patients. These findings might be reassuring, but

the selection bias inherent in survey studies may underly this observation. Patients with more severe

disease (for example, those who were still in a hospital or an ICU) were less likely to respond to the

survey. This may lead to an incorrect conclusion of a more benign course of the disease in MS. On

the other hand, symptomatic people were more motivated to participate in the survey (or

asymptomatic patients were less likely to participate). This selection bias could lead to finding a

higher proportion of the disease-suspects when compared to the general population.

The most important independent risk factor for being categorized in the COVID-19 suspected

group, aside from having close contact with people with upper respiratory symptoms, was the DMT

category. Patients who were on a B-cell depleting antibody, as compared to patients on other none-

lymphocyte-depleting, non-cell-trafficking inhibitor DMTs, had a higher risk of being in the

COVID-19-suspect group. The only two patients who needed hospitalizations were on a B-cell

depleting antibody. However, all patients with MS on B cell depleting agents suspected for COVID-

19 were eventually recovered. This finding is also supported by other groups who studied the course

of COVID-19 in patients with MS.

B-Cell depleting therapies like rituximab and ocrelizumab have striking therapeutic effects in MS.

However, they remove a large portion (or all) of circulating B-cells and impair the humoral arm of

the immune system and increase the risk of Infections. Recent studies on immune response against

SARS-C0V-2 infection reiterate the fact that intact adaptive immune response and generation of

neutralizing antibodies against the virus play protective roles in the host during the symptomatic

period and less severe phase of the disease. Therefore, patients with MS treated with B-cell

40
depleting agents might be more prone to COVID-19. However, patients with X-linked

agammaglobulinemia (XLA) who suffer from lack of B-cells showed full recovery following

COVID-19 infection, implying that neutralizing antibodies might be less crucial in the later phase

of infection and its recovery. XLA patients receive therapeutic IVIG intermittently that may also

contribute to their recovery from COVID-19.

It is possible that patients who were on the DMTs other than B-cell depleting antibodies were

protected from the infection. In that case, the differences were driven by the patients receiving

interferons and DMF: Among patients on interferons or DMF, the proportion of patients in the

COVID-19 group was smaller than the non-COVID-19 group. Antiviral properties of type I

interferons that may subside SARS-COV-2 infection could be relevant to this finding. Patients on

DMF have less inflammatory T-cell responses. It has been shown that a strong virus-specific T-cell

response could lead to more severe disease in another coronavirus respiratory disease (SARS-Cov-1

infection.The Italian preliminary data also demonstrate that patients who were on DMF recover well

from COVID-19. We did not observe any differences in the proportion of fingolimod- and

natalizumab-treated patients between the COVID-suspect group and the rest of the participants.

None of the patients who participated in the survey received other lymphocyte-depleting

medications, such as alemtuzumab and cladribine. These findings are preliminary, the number of

participants with the outcome (being in the COVID-19-suspect group) was small, and these results

should be interpreted with caution.

We did not find an association between the age, type of MS, level of disability, the degree of

observing "stay at home" recommendations, and the risk of being in the COVID-19 group. There is

probably a lag between the effectiveness of quarantine measures and a reduction in the risk of an

epidemic infection. That might explain our observation that in the early days of the epidemic, there

was no association between the degree of observing quarantine recommendations and the risk of

being in the COVID-19-suspect group.

41
In the multivariable analysis, longer disease duration seemed to be an independent protective factor.

Patients with longer disease duration might be more disabled (lower chance to go out and be

exposed) and are less likely to be on DMTs. Although we adjusted our models for the disability

levels and the DMTs, the residual confounding may explain this observation.

This study provides an early overview of the severity and the risk factors for developing COIVD-19

in patients with MS in the early days of the epidemic in Iran. A relatively large sample size and

used a multivariable model for finding independent risk factors. The study has many limitations.

We alluded to biases that could have led to the observations of a higher proportion of disease-

suspect patients and a more benign course in our study. None of our patients were tested with the

gold standard testing for the diagnosis of COVID-19 (the PCR of the nasopharyngeal swab). We

were also not aware of the spectrum of symptoms associated with COVID-19 at the time of study

design. For example, anosmia has been reported to be a common symptom of COVID-19, but it was

not part of the questionnaire, and we may have underestimated the number of patients with less

severe symptoms.

It was found that a relatively high proportion of patients with MS developed symptoms suggestive

for COVID-19 during the early days of the epidemic in Iran, but no patient required intensive care

or intubation. Different DMTs may increase or decrease the susceptibility to the COVID-19

infection.

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity

and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2

42
(SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS

(PwMS).

Objective: The objective of this study was to describe the overall risk of coronavirus disease 2019

(COVID-19) infection, severe disease course, and potential population-level predictors of COVID-

19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus

erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and

clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database

are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies.

Methods: The IBM® Explorys electronic health record database of > 72,000,000 patients from US

healthcare networks identified patients with MS or SLE, with and without polymerase chain

reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths

among DMT classes were compared using logistic regression (adjusted for age, sex, body mass

index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-

19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety

Database.

Results: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were

COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity

score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also

identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when

treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p <

0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen

Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with

intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel

fumarate, or fampridine.

43
Conclusions: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with

a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were

associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an

increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen

MS therapies were consistent with the Explorys database and MS literature, illustrating the

replicability and power of this approach.

Treatment of Multiple Sclerosis from Covid medication: COVID-19 vaccine technology

may unlock new MS treatment

In January, the German biotechnology company, BioNTech, reported that a new vaccine using the

same mRNA techniques found in the Pfizer COVID-19 vaccine was proven effective in treating or

stopping EAE in lab mice.1

44
Let’s decode

● EAE (experimental autoimmune encephalomyelitis): the rodent equivalent of MS.2

● Messenger ribonucleic acid (mRNA): A protein molecule found in every cell of the human

body and considered a precursor to DNA — our genetic code. mRNA plays a critical role in

the cellular processes we need to function.3

While COVID-19 is a virus, what researchers now know about its behavior in the immune system

has identified potential new ways to stop MS symptoms and progression.

We know that MS is the outcome of a malfunctioning immune system. As with all autoimmune

diseases, the immune system in a person with MS attacks healthy tissues. In MS, the myelin coating

the nerves in the brain and spinal cord is the target. The result? Disruptions of signaling between the

brain and other parts of the body. These miscommunications lead to problems we’re all familiar

with: muscle control, sensory overload or failure, and other challenges which worsen with disease

progression.

How mRNA research can help people with MS

The Johannes Gutenberg University team in Mainz, Germany who performed the research for

BioNTech adapted their idea for an MS-specific vaccine from current mRNA vaccine designs

specific to COVID-19. Instead of targeting a virus, however, their design wraps fatty substances

around the genetic MS coding in cells to prevent the immune system from successfully attacking

them.4

Results from research published in Science earlier this year showed that their MS-specific vaccine

stopped active symptoms in laboratory mice with EAE and prevented further damage with early

signs of MS.

45
Hope in mRNA

This treatment has added value: while our current MS medications generally compromise our

immune systems in order to work, mRNA does not. 5 That spells hope for millions of people with

MS who fear even the smallest infection will land them in the hospital.

Of course, we still need to see research that transfers to human subjects, showing effectiveness and

safety. But given the treasury of what we now know about mRNA vaccines in general (thanks to

COVID-19 vaccine research), this is fantastic news. Some now declare it the “mRNA revolution.”

FDA approves new nasal treatment with roots in COVID-19 treatment for SPMS

Recently, the FDA approved the use of an antibody, delivered in a nasal spray, to treat people

with secondary-progressive multiple sclerosis (SPMS).

More decoding

● The antibody, foralumab, belongs to the “-mab” family of monoclonal antibodies.

● What do “-mabs” do? They’re the good guys. They mimic the antibodies that your immune

system already naturally produces in response to invaders. Consider them your personal

immune system army.

● Other familiar “-mabs” include ocrelizumab (Ocrevus), daclizumab (Zinbryta),

alemtuzumab (Lemtrada), rituximab (Rituxan), and natalizumab (Tysabri).8

This will be the first time a nasal antibody will be administered to someone with SPMS. Treatment

with foralumab may start experimentally with a single patient at Brigham and Women’s Hospital at

Harvard University in Boston as soon as June 2021. Researchers expect the treatment protocol to

last for six months.9

46
Famed MS researcher Howard Weiner developed the nasal spray. It’s already undergone Phase 1

trials to prove safety and effectiveness. It’s hoped that this new approach will “revolutionize”

treatment for SPMS, which lacks more and better therapies.9

The COVID-19 research connection

Foralumab works using an interaction between the gastrointestinal and nasal mucosal immune

systems. This interaction modulates the immune system response and reduces inflammation both

locally and systemically.10

Last November, Tiziana started clinical trials of foralumab — not as a treatment for MS, but as a

way to treat rampant severe COVID-19 in Brazil. By February of this year, the research showed that

foralumab suppressed the dangerous symptom of lung inflammation quickly and enhanced both

senses of smell and taste in people receiving the treatment.12

Treating your MS with a nasal spray? It seems like another miracle in the works for both those with

SPMS and those struggling with COVID-19.

Psoriasis and Covid-19:

This case study has presented the largest and first global case series of COVID-19 in people with

psoriasis. Of 374 patients from 25 countries reported by clinicians, 93% fully recovered from

COVID-19. Older age, male sex, and nonwhite ethnicity were associated with greater risk of

47
hospitalization for COVID-19, in addition to chronic lung disease. Comorbidities such as

hypertension, cardiovascular disease, and chronic liver disease were more prevalent in hospitalized

patients than in those not hospitalized. The data also indicate an association between use of

biologics for psoriasis and reduced risk of hospitalization compared with the risk associated with

nonbiologic systemic therapies. We cannot exclude the possibility that unmeasured confounders

may be driving this association: for example, our patient-reported data (1626 participants across 48

countries) suggest that COVID-19 risk-mitigating behaviors (social isolation) may differ between

psoriasis treatment groups. Finally, no significant difference was found in risk of hospitalization

between different classes of biologics. Further investigation of the higher rate of hospitalization

observed among patients using IL-23 inhibitors (compared with TNF or IL-17 inhibitors) in larger

data sets is warranted.

The baseline characteristics of the international case series suggest that the findings are likely to be

applicable to people with moderate-to-severe psoriasis because 90% of those reported were taking

systemic therapies and there was a high prevalence of comorbidities. The study underscores older

age, male sex, nonwhite ethnicity, and comorbidities as important risk factors for adverse COVID-

19 outcomes in people with psoriasis, which is consistent with those risk factors already established

for the general population. A cohort study of 17 million adults in the United Kingdom found that

death from COVID-19 was associated with comorbidities, including cardiovascular disease,

diabetes, obesity, reduced kidney function, and chronic liver disease. 6 Similarly, a case series of

44,672 patients with COVID-19 in China showed that cardiovascular disease, hypertension, and

diabetes were risk factors for death. There are very limited data on psoriasis, with 4 regional

psoriasis case series in Northern Italy, suggesting no increased rate of hospitalization or death from

COVID-19 in those receiving biologics compared with the rates among the local population. Only 6

patients were hospitalized across the 4 reports, with few patients with nonsevere COVID-19. hence,

risk factors for adverse COVID-19 outcome could not be characterized. We addressed this through

a larger collection of cases that was more diverse with respect to geography, psoriasis therapies, and

48
COVID-19 severity and outcomes. The comprehensive capture of clinician-reported demographic

and clinical variables enabled adjustment for important covariates in our logistic regression

analysis.

The finding of differential hospitalization risk associated with different treatment groups builds on

the emerging literature across IMIDs. A recent single-center COVID-19 case series of 86 patients

with IMIDs from New York (14 of whom had psoriasis) observed that use of biologics was lower

among those hospitalized for COVID-19 (6 of 14 [43%]) than among those not hospitalized (50 of

72 [69%]). Use of nonbiologic systemic agents, including the common psoriasis therapy

methotrexate, was higher among hospitalized patients than among those not hospitalized.

Our data also align with findings from global clinician-reporting COVID-19 registries in

inflammatory bowel disease (IBD) (525 patients across 33 countries) and rheumatic disease (600

patients across 40 countries). The hospitalization and case fatality rates were 31% and 3%,

respectively, in IBD, and 46% and 9%, respectively, in rheumatic disease (vs 21% and 2% in our

psoriasis data set). Severe COVID-19 was associated with older age and comorbidities in both

studies. TNF inhibitor use was associated with decreased risk of COVID-19–related hospitalization

among patients with rheumatic disease (OR = 0.4; 95% CI = 0.19-0.81) and decreased risk of

hospitalization or death among those with IBD (OR = 0.6; 95% CI = 0.38-0.96). These findings,

together with our data, contrast with pre–COVID-19 observational data, in which use of biologics

(including TNF inhibitors) was associated with an increased risk of serious infections (eg, a higher

incidence of lower respiratory tract infections and/or pneumonia has been observed for infliximab

compared with methotrexate). A meta-estimate of phase III randomized controlled trials of IL-17

inhibitors in psoriasis also indicated an increased risk of respiratory tract infections compared with

placebo (OR = 1.31; 95% CI = 1.05-1.62); however, a similar analysis (albeit it with smaller sample

sizes) found no statistically significant signal associated with IL-23 inhibitor use (OR = 1.15; 95%

CI 0.88-1.49). Phase III trial data also suggest that use of psoriasis biologics (TNF, IL-17, and IL-

49
23 inhibitors) is not associated with increases in rates of viral infections such as influenza compared

with placebo, which is consistent with the data from long-term registries and studies of other IMIDs.

Given the cytokine upregulation from aberrant immune activation observed in severe COVID-19,

there is biologic plausibility for a protective effect of cytokine-targeted biologics on adverse

outcomes, compared with the effect of broader immunosuppressants that may detrimentally

suppress host antiviral immunity. This notion is currently under evaluation in trials of repurposed

IMID biologics in patients with COVID-19. Existing reports of elevated plasma levels of TNF and

IL-17 in patients manifesting severe COVID-19 also align with our observation of a lower

hospitalization rate in individuals receiving TNF inhibitors or IL-17 inhibitors compared with the

rate in those receiving IL-23 inhibitors. Given the close interplay between IL-17 and IL-23

cytokines (IL-23 promotes the terminal differentiation, proliferation, and activation of IL-17–

secreting TH17 cells and the more established role of the IL-23/IL-17 axis in bacterial and fungal

immunity (as opposed to viral defense), these observations require further study. We were unable to

draw firm conclusions because our sample numbers limited the power to detect all but large

differences in hospitalization risk between biologic classes. Inhibitors of TNF, IL-17, and IL-23 are

widely used for the treatment of moderate-to-severe psoriasis, so further accrual of cases over time

will enable more robust interrogation of the differential risks associated with different biologic

classes, which has important implications for clinical practice.

Alternatively, the association between use of biologics and reduced hospitalization may not be

causal but may instead be due to unmeasured confounders. The patient-reported data suggest

increased risk-mitigating behavior (social isolation) in individuals receiving biologics compared

with the risk in those receiving nonbiologic systemic agents, which may reflect public perceptions

of differential risk associated with different treatments. Social isolation may influence the initial

exposure dose of SARS-CoV-2, which may affect the viral load and clinical course of COVID-19.

Behavioral variation between treatment groups and the consequent impact on COVID-19 risk

50
and/or severity warrant urgent further investigation because it is potentially relevant for public

health policy.

Major strengths of this case series are its global reach and size. The speed with which data have

been accrued has enabled the timely release of results in response to the current global public health

emergency. As the largest international study of COVID-19 outcomes in patients with psoriasis, the

findings are more generalizable than those of the regional reports published to date. The key

demographic associations with hospitalization for COVID-19 (sex, age, and ethnicity) in our

psoriasis data set are in keeping with prior findings in the general population, which suggests robust

data capture.

Information on the registries was disseminated worldwide, but the larger numbers of patients from

Spain, Italy, and the United Kingdom (albeit areas of high COVID-19 prevalence) indicate potential

ascertainment bias, which limits the generalizability of the results. Although our hospitalization rate

of 22% is comparable to that in other global IMID registries, more severe COVID-19 cases may be

overrepresented because these may have been preferentially brought to the attention of clinicians. In

contrast, patients who have died or those remaining in the hospital may not yet have been reported.

The higher hospitalization rate in Spain may represent a selective capture of severe cases or

different international thresholds for hospital admission; the latter is a limitation of using

hospitalization as a proxy for severe COVID-19. Reassuringly, a sensitivity analysis excluding

Spanish cases did not change our conclusions, and differences in rates of death and mechanical

ventilation among patients with psoriasis receiving biologics versus among those receiving

nonbiologic systemic therapies were consistent with our primary findings for hospitalization.

Diverse COVID-19 testing practices may also have affected reporting (eg, preferential testing of

severely ill and/or hospitalized patients), although we encouraged submission of suspected cases

and our sensitivity analysis restricted to patients with only confirmed COVID-19 yielded results to

similar those of the main analysis.

51
The case series is dominated by patients with moderate-to-severe psoriasis; therefore, our findings

may not be generalizable to those with milder psoriasis. The majority of clinician-reported patients

were receiving biologics, which contrasts with our patient-reported data. If this represents a

different propensity for clinicians to report patients receiving different types of treatment, then

together with a higher likelihood of hospitalized cases being reported, this could lead to inflated

effect size estimates on account of selection bias. In contrast to the limitations of clinician-reported

data, a potential limitation of the self-report data set is exposure misclassification, but it is

reassuring that the overall baseline characteristics of both registries are comparable.

Although not an objective of this study, the clinical course of COVID-19 in individuals with and

without psoriasis cannot be compared owing to the lack of a matched control group from the

general population. COVID-19 outcomes in those receiving biologics in our study also cannot be

directly compared with the outcomes studies of the general population because of fundamental

differences in the ascertainment of cases. However, the observed median length of hospital stay and

COVID-19 symptom characteristics in the biologic-treated clinician-reported case series is similar

to the median lengths published for general populations. For example, the median length of hospital

stay for patients with psoriasis and COVID-19 who were receiving biologics in our study (14 days

[IQR = 6-23 days]) is similar to that of 1099 hospitalized patients with COVID-19 across 552

hospitals in China (12 days [IQR = 10-14 days]). The 3 most common symptoms of COVID-19 in

both the Chinese cohort and our patients who were receiving psoriasis biologics were fever, cough,

and fatigue.

The incidence of COVID-19 in psoriasis cannot be determined on account of the lack of

denominator (source population) data and uncertainty regarding those patients with psoriasis and

COVID-19 who were not reported. The incidence of COVID-19 in individuals receiving particular

therapies also cannot be deduced; however, future linkage to pharmacovigilance registry data

should facilitate this.

52
In this large international series of patients with psoriasis and COVID-19, use of biologics was

associated with a reduced risk of adverse COVID-19 outcome when compared with the risk

associated with use of nonbiologic systemic agents. This effect appeared to be primarily associated

with use of TNF and IL-17 inhibitors; however, further investigation of the observed differential

rate of hospitalization between different classes of biologics is warranted. The accumulation of

further data is required to clarify these observations before any recommendations for changes in

clinical practice can be considered. Possible selection bias should be addressed through robust

global clinician and patient participation in COVID-19 registries and alternative study designs such

as cohort studies. This will open avenues for characterizing the determinants of additional COVID-

19 outcomes and the impact of specific treatments at higher resolution.

53
Psoriasis medication in treatment of Covid-19:

As with other autoimmune conditions, psoriasis patients may have a higher-than-average risk of

contracting COVID-19 (novel coronavirus) or developing serious complications, though more

research on this patient population is needed. It is too preliminary to say whether or to what degree

people with psoriasis could be affected differently by COVID-19. An observational study that aims

to determine how prevalent COVID-19 is in psoriasis patients who are using immunosuppressive

medication is currently underway in Italy.

Recently, a study from the Perelman School of Medicine at the University of Pennsylvania found

that psoriasis patients who use an IL-17 inhibitor (secukinumab, ixekizumab, or brodalumab) were

more likely to develop respiratory tract infections during previously conducted drug trials. They did

not specifically look at risk for COVID-19, as these trials were conducted prior to the pandemic.

The flip side: IL-17 inhibitors have shown some promise as a potential treatment for COVID-19

patients who experience a cytokine storm.

One small case study, published recently in the New England Journal of Medicine, found that

people with inflammatory conditions, including psoriasis, who took biologics and had COVID-19

were not any more likely to develop complications compared to inflammatory disease patients who

were not using these drugs.  But larger studies may yield different findings, and there are other

reasons to be concerned. “People with psoriasis are also known to have a greater incidence of co-

occurring chronic medical conditions, such as heart disease, that can put one at higher risk for

COVID-19 complications,” says California-based dermatologist Cynthia Bailey, MD, a diplomate

of the American Board of Dermatology. Having psoriasis during the coronavirus pandemic may

also be problematic because your skin is much more apt to become irritated from all the frequent

hand washing and sanitizing. You may also develop skin cracks or sores. “I wonder if the virus can

pass through open skin sores, but I could not find any scholarly scientific information to suggest

54
that it has been seen,” says Dr. Bailey. At this time, it is believed that COVID-19 is primarily

transmitted when someone inhales virus particles, or touches them and then touches their mouth,

nose, or possibly eyes. Even if direct skin transmission does not turn out to be possible, breaks in

the skin’s barrier and irritation are still serious issues, says Joshua Zeichner, MD, director of

Cosmetic and Clinical Research in the Department of Dermatology at The Mount Sinai Hospital in

New York City. “The skin on your fingers is generally where the virus lives, and when you touch it

you can spread it to your face,” he explains.

People who are prone to skin inflammation and scaly plaques on their hands may have a hard time

washing their hands thoroughly. “If you can’t wash your hands well you may be more likely to

spread the virus if you come in contact with it,” he adds. Dr. Bailey also has concerns about hand

hygiene in patients experiencing psoriasis flares. “Psoriatic skin lesions are characterized by a lot of

scale, and these are rough places where viral particles may be able to lodge and resist easy removal

by washing,” she says.

In clinical trials, some medications used for the treatment of other ailments have also shown

promising results for the treatment of coronavirus patients. Itolizumab, a drug used to cure skin

ailment psoriasis, is one such medication. Based on promising clinical trial data, the Drugs

Controller General of India (DCGI) has approved restricted emergency use of Itolizumab injection

for treating COVID-19 patients with moderate to severe acute respiratory distressItolizumab is a

monoclonal antibody injection approved for the treatment of psoriasis – a skin disorder that causes

skin cells to multiply up to 10 times faster than normal. It is made from lab-made proteins that act

like human antibodies in the immune system to fight against foreign molecules. Biocon conducted

trails to see Itolizumab’s effect on Covid-19 patients. The results of the trials showed improvement

in PaO2 and O2 saturation related to lung function. The drug also significantly reduced key

inflammatory markers IL-6, TNFα, etc., thereby preventing hyper-inflammation in COVID-19

patients. 

55
Itolizumab is the first novel biologic therapy to be approved anywhere in the world for treating

patients with moderate to severe COVID-19 complications, Biocon Ltd. in a statement. The

company added that it has repurposed Itolizumab for the treatment of cytokine release syndrome in

moderate to severe ARDS patients due to COVID-19.

Itolizumab was used to treat eight COVID-19 patients, who had an oxygen saturation of less than

80%, in Lok Nayak Hospital. In a statement, Dr Suresh Kumar, medical director, Lok Nayak

Hospital, said that the patients did extremely well even with a single dose of Itolizumab. They

recovered completely after treatment with Itolizumab and got discharged, he added.

Areas of current and future research (e.g., IL-35):

The most recently identified potential therapeutic target in inflammatory diseases, including PsO

and MS, involves IL-35. IL-35 is a more recently identified member of the IL-12 cytokine family

and is secreted primarily by regulatory T cells (T regs). IL-35 is also uniquely an immunosuppressive

cytokine that plays a pivotal role in the function of T regs and their immunoregulatory activity. Both

PsO and MS, among other autoimmune inflammatory diseases, have abnormal IL-35 expression,

making IL-35 a potential new focus of therapeutic strategies.

Another potential treatment for both MS and PsO in recent literature lies in the properties

of mesenchymal stem cells (MSCs). MSCs have the capabilities of modulating immune

properties and exerting anti-inflammatory effects making them an alluring potential

therapy in autoimmune inflammatory conditions. In a recent study, human embryonic

(hE)-MSC transplantation resulted in the dramatic reduction of T h1 and Th17 cytokines in

mice with imiquimod-induced PsO-like dermatitis. There have been a relatively larger

number of studies regarding MSC transplantation in the treatment of MS, many of them

also showing promise, especially in comparison to current disease-modifying options, for

56
the effective treatment of MS. Further studies are needed to determine the efficacy of

MSC and the most promising cell origin as a therapy for both MS and PsO.

57
CONCLUSION:

The data regarding the association between PsO and MS are overall inconsistent and

conflicting. Smaller studies suggest that there may be an association and the few larger

studies that have been conducted report no significant association between PsO and MS.

Further study to verify or reject this association is warranted as uncovering the

relationship between these two diseases could lead to the discovery of common

mechanisms and genetic or environmental causes that could be of substantial value in the

diagnosis and management of both diseases. Until then, dermatologists and other treating

physicians alike may find it appropriate to screen for MS symptoms in patients with PsO

so that timely referral to a neurologist can occur if necessary.

58
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