Received: 26 February 2023 | Revised: 23 July 2023 | Accepted: 30 July 2023

DOI: 10.1111/exd.14910

C O N C I S E C O M M U N I C AT I O N

Clinical and patient-­reported outcomes from the first 4 years of

a Psoriasis Biologics Registry in Singapore

Xuan Qi Koh1 | Hazel H. Oon1,2 | Wei-­Sheng Chong1 | Bernett Lee3 |

Xiahong Zhao1 | Eugene S. T. Tan1

1
National Skin Centre, Singapore,
Singapore Abstract
2
Skin Research Institute of Singapore, Interim analysis of the National Skin Centre Singapore Psoriasis Biologics Registry
Singapore, Singapore
3
(SINGPSOR) from August 2017 to May 2021, in which 58 patients were analysed,
Centre for Biomedical Informatics,
Nanyang Technological University, showing that those receiving biologic treatment had significantly more severe pso-
Singapore, Singapore riasis based on PASI (Psoriasis Area and Severity Index), BSA (body surface area) and
Correspondence PGA (Physician Global Assessment) measures at baseline, demonstrated a statistically
Xuan Qi Koh, National Skin Centre, non-­significant trend towards greater improvement with treatment, and had a lower
Singapore, Singapore.
Email: xuanqi.koh@mohh.com.sg percentage of adverse events compared to those receiving conventional systemic
therapy. Future analyses of SINGPSOR, with larger sample size and longer follow-­up,
Funding information
Johnson and Johnson, Grant/Award will be invaluable to further characterize these patients and their treatment outcomes.
Number: NSC/2021–­0 0083
KEYWORDS
adalimumab, biologics, psoriasis, registries, ustekinumab

1 | BAC KG RO U N D 2 | QU E S TI O N S A D D R E S S E D

Biologic registries have been successfully implemented in many
countries and regions worldwide, and interim analyses of such
registries deliver timely updates not only on new observations of
specific experiences.1–­5
rare adverse events, but also on region-­
The National Skin Centre Singapore Psoriasis Biologics Registry
(SINGPSOR) was established in August 2017 to systematize the rou-
tine collection of safety and efficacy data for patients with psoriasis
in Singapore who are on biologic treatments.
Whilst retrospective analyses of other larger international reg-
istries have already provided significant contributions to the real-­
world experience of biologic use in psoriasis, this study marks
the inaugural interval analysis since the commencement of the
SINGPSOR and aims to plug the current gap in data on treatment
outcomes of psoriasis in Singapore. Routine interval analyses of the
registry are necessary for the timely detection of changes in clinical
trends and adverse events related to use of biologics, as well as high-
lighting any unique nuances in our local population, for example with
regards to drug survival.6,7
1) Is there a significant difference between the baseline demo-
graphic and disease severity of psoriasis patients who are treated
with conventional systemic therapy compared to those treated
with biologics in Singapore?
2) Is there a significant difference between the clinical efficacy and
safety trends between psoriasis patients treated with conven-
tional systemic therapy compared to those treated with biologics
in Singapore?
3 | E X PE R I M E NTA L D E S I G N
Patients with a clinical diagnosis of psoriasis who were newly started
or switched to a conventional systemic or biologic therapy within the
past 6 months were enrolled in SINGPSOR. Eligible patients were
identified by their attending dermatologists during routine visits at
the psoriasis subspecialty clinic in the National Skin Centre Singapore
after August 2017. The conventional systemic therapy group serves

© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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2 KOH et al.

TA B L E 1 Baseline demographics comparing patients receiving conventional systemic therapy and those receiving biologic treatment.
(A) Comparison of baseline demographics of 58 analysed patients at enrolment. (B) Comparison of demographics and baseline severity of
patients at the start of the respective treatment episodes.

(A)

Summary statistics All (n = 58) Conventional (n = 19) Biologic (n = 39) p-­Value

Age (years, mean ± SD) 45.4 ± 14.9 36.7 ± 13.1 49.7 ± 13.9 0.0016
Gender
Male 41 (70.7%) 14 (73.7%) 27 (69.2%) 1.0000
Female 17 (29.3%) 5 (26.3%) 12 (30.8%)
Ethnicity
Chinese 45 (77.6%) 12 (63.2%) 33 (84.6%) 0.1916
Malay 8 (13.8%) 4 (21.1%) 4 (10.3%)
Indian 3 (5.2%) 2 (10.5%) 1 (2.6%)
Others 2 (3.4%) 1 (5.3%) 1 (2.6%)
Type of psoriasis
Chronic plaque psoriasis 54 (93.1%) 17 (89.5%) 37 (94.9%) 0.5907
Others 6 (10.3%) 4 (21.1%) 2 (5.1%) 0.0828
Psoriatic arthritis (missing data for two people)
Yes 12/56 (21.4%) 3/18 (16.7%) 9/38 (23.7%) 0.7320
No 44/56 (78.6%) 15/18 (83.3%) 29/38 (76.3%)
Family history of psoriasis in first degree relative (missing data for one person)
Yes 10/57 (17.5%) 3 (15.8%) 7/38 (18.4%) 1.0000
No 47/57 (82.5%) 16 (84.2%) 31/38 (81.6%)
Age of onset and duration of psoriasis
Age of onset (years, mean ± SD) 27.6 ± 12.5 26.1 ± 12.7 28.3 ± 12.5 0.5899
Duration of psoriasis (years, mean ± SD) 17.8 ± 11.6 10.6 ± 11.5 21.4 ± 10.1 0.0004
Comorbidities
Diabetes mellitus 12 (20.7%) 3 (15.8%) 9 (23.1%) 0.7326
Hypertension 17 (29.3%) 4 (21.1%) 13 (33.3%) 0.3775
Dyslipidaemia 9 (15.5%) 3 (15.8%) 6 (15.4%) 1.0000
Ischaemic heart disease 1 (1.7%) 0 (0.0%) 1 (2.6%) 1.0000
Non-­alcoholic fatty liver disease 9 (15.5%) 1 (5.3%) 8 (20.5%) 0.2466
Alcoholic liver disease 1 (1.7%) 0 (0.0%) 1 (2.6%) 1.0000
Viral hepatitis 4 (6.9%) 1 (5.3%) 3 (7.7%) 1.0000
Chronic kidney disease 1 (1.7%) 0 (0.0%) 1 (2.6%) 1.0000
Depression/ anxiety 3 (5.2%) 1 (5.3%) 2 (5.1%) 1.0000
Previous treatments
NBUVB 37 (63.8%) 9 (47.4%) 28 (71.8%) 0.0865
PUVA 3 (5.2%) 2 (10.5%) 1 (2.6%) 0.2475
Phototherapy (not specified) 3 (5.2%) 0 (0.0%) 3 (7.7%) 0.5437
Acitretin 24 (41.4%) 4 (21.1%) 20 (51.3%) 0.0458
Cyclosporin 35 (60.3%) 7 (36.8%) 28 (71.8%) 0.0208
Hydroxyurea 13 (22.4%) 1 (5.3%) 12 (30.8%) 0.0426
Methotrexate 39 (67.2%) 9 (47.4%) 30 (76.9%) 0.0370
Adalimumab 6 (10.3%) 1 (5.3%) 5 (12.8%) 0.6525
Infliximab 2 (3.4%) 0 (0.0%) 2 (5.1%) 1.0000
Secukinumab 2 (3.4%) 0 (0.0%) 2 (5.1%) 1.0000
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KOH et al. 3

TA B L E 1 (Continued)

(A)

Summary statistics All (n = 58) Conventional (n = 19) Biologic (n = 39) p-­Value

Ustekinumab 4 (6.9%) 0 (0.0%) 4 (10.3%) 0.2921

Efalizumab 1 (1.7%) 0 (0.0%) 1 (2.6%) 1.0000

(B)

Summary Statistics Conventional (n = 36) Biologic (n = 75) p-­Value

Age (years, mean ± SD) 36.8 ± 11.7 48.6 ± 13.1 <0.0001

Gender
Male 26 (72.2%) 52 (69.3%) 0.8270
Female 10 (27.8%) 23 (30.7%)
Ethnicity
Chinese 25 (69.4%) 62 (82.7%) 0.2807
Malay 7 (19.4%) 9 (12.0%)
Indian 3 (8.3%) 2 (2.7%)
Others 1 (2.8%) 2 (2.7%)
BSA (n; median [range]) 33; 10 (2, 70) 72; 20 (1, 90) 0.0020
PASI (n; median [range]) 25; 9.7 (2, 21.7) 57; 14.4 (1.2, 38.5) 0.0019
DLQI (n; median [range]) 16; 2 (1, 21) 39; 5 (0, 29) 0.179
PGA score
Clear (PGA 0) 0 0 0.0390
Almost clear (PGA 1) 8 (25.8%) 5 (6.9%)
Mild (PGA 2) 13 (41.9%) 41 (56.9%)
Moderate (PGA 3) 10 (32.3%) 26 (36.1%)
Severe (PGA 4) 0 0

Abbreviations: BSA, body surface area; DLQI, Dermatology Life Quality Index; N, number; PASI, Psoriasis Area and Severity Index; SD, standard
deviation.

as a comparator against the biologic group for this registry. Registry 4 | R E S U LT S

data were updated approximately every 4–­8 months for each patient,
depending on their routine visit schedule. Information collected in-
cluded demographics, clinical characteristics, treatments, adverse
events, physician-­rated and patient-­reported outcome measures.
For this interval analysis, local ethics board approval was ob-
tained to extract deidentified data of patients enrolled in SINGPSOR
between 14 August 2017 and 1 May 2021. All patients enrolled in
this period were included in the analysis of baseline demograph-
ics, but only those who had at least two data collection timepoints
were analysed for treatment safety and efficacy. Statistical analy-
sis was performed using R version 3.5.3 software. Significance was
assessed at a level of 0.05. Improvements were assessed based
on the last documented visit of each patient using the clinical end
points of Psoriasis Area and Severity Index (PASI), Dermatology Life
Quality Index (DLQI), body surface area (BSA) and Physician Global
Assessment (PGA). Improvements were scored as yes or no using
PASI 50, PASI 75 and PASI 100, as well as 50%, 75% and 100% re-
duction from baseline scores for DLQI, BSA and PGA. The differ-
ences in improvements between the groups were assessed using the
logrank test using right censoring.
A total of 92 patients were enrolled, of whom 58 had at least two
visits. There were no significant differences in baseline demograph-
ics between the 92 enrolled patients and 58 analysed patients in
terms of age, gender, ethnicity and duration of psoriasis (Table S1).
Total of 19 and 39 patients originally received conventional systemic
treatment and biologic treatment, respectively. However, some had
treatment changes, thus generating 114 individual treatment epi-
sodes; of these, three treatment episodes had dual treatments and
were excluded from the analysis. Each treatment episode was de-
fined as the period from start to end in which the patient was receiv-
ing either a conventional systemic treatment or biologic treatment,
with or without topical therapy. At enrolment, patients treated with
biologics were older (49 vs 36 years, p = 0.0016) and had longer
duration of psoriasis (21 vs 10 years, p < 0.001) compared to those
treated with conventional systemic therapies (Table 1A).
Baseline disease severity scores were compared using Wilcoxon
rank sum (Mann–­
Whitney) test (Table 1B). When analysed as two
broad groups (conventional systemic therapy vs biologics), the baseline
BSA, PASI and PGA scores taken at the start of each treatment episode
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4 KOH et al.

were more severe in patients receiving biologics (median BSA 20% vs
10%, p = 0.002; median PASI 14.4 vs 9.7, p = 0.002; PGA comparison
p = 0.039). The median DLQI was 5.0 for those receiving biologics
compared to 2.0 for those receiving conventional systemic therapy, al-
though this comparison did not reach statistical significance (p = 0.179).
The length of time between each visit for each patient was plot-
ted and revealed a continuous distribution. As such, Kaplan–­Meier
estimates were used to compare the percentage of patients in each
group who achieved clinical end points of PASI 50, PASI 75 and
PASI 100 based on the PASI score at the last documented visit of
each patient on that particular treatment. Kaplan–­Meier estimates
were similarly employed to evaluate achievement of 50%, 75% and
100% reductions from baseline DLQI and PGA scores when possi-
ble. Graphical representation of Kaplan–­Meier curves demonstrates
that overall the proportions of patients receiving biologic treatment
who achieved 75% or greater improvement in DLQI, 50% or greater
improvement in BSA, and 50% improvement in PGA, PASI 50 and
PASI 75 were higher than those receiving conventional systemic
treatment, although none of these analyses reached statistical sig-
nificance (Figure 1A–­E).
Fisher's exact test was used to compare efficacy outcomes
between the conventional systemic and biologic groups at week
52. There was no statistical difference in the proportion of pa-
tients achieving 50% or greater improvement in BSA, PASI and
DLQI, though there was a trend towards higher efficacy with
achieving at least 75% improvement in BSA in the biologic group
(Table S2).
Adverse events are listed in Table 2. These were either reported
by patients or discovered during routine clinical and laboratory
monitoring at intervals tailored to the individual patient's comor-
bidities or treatment. The proportion of patients who experienced
an adverse event was 30.6% amongst those receiving conven-
tional systemic treatment and 8% amongst those receiving biologic
treatment.

(A) Cumulative responder percentage (B) Cumulative responder percentage (C) Cumulative responder percentage
for 50% improvement in BSA for 50% improvement in PGA for PASI 50

n=79, Conventional systemic group = 27, n=74, Conventional systemic group = 23, n=45, Conventional systemic group = 8,
Biologic group = 52, logrank p=0.83 Biologic group = 51, logrank p=0.69 Biologic group = 37, logrank p=0.53

(D) Cumulative responder percentage (E) Cumulative responder percentage

for PASI 75 for 75% improvement in DLQI

n=45, Conventional systemic group = 8, n=26, Conventional systemic group = 7,

Biologic group = 37, logrank p=0.90 Biologic group = 19, logrank p=0.61

F I G U R E 1 Kaplan–­Meier estimates for achievement of improvement in BSA, PGA, DLQI and PASI scores (A–­E). BSA, body surface area;
DLQI, Dermatology Life Quality Index; n, number; PASI, Psoriasis Area and Severity Index; PGA, Physicians Global Assessment. The blue
dots represent the cumulative responder percentage based on last measured clinical outcome from individual patients on conventional
systemic therapy. The red dots represent the cumulative responder percentage based on the last measured clinical outcome from individual
patients on biologic treatment.
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KOH et al. 5

TA B L E 2 Adverse events per treatment.

previously observed findings in retrospective local cohorts9,10 interna-
Treatment (n) Adverse events (n; % of total patients) tional registries11,12 and systematic reviews.8,13
(A) Adverse events in those who received conventional systemic The two potential confounders in our study were older age at

Acitretin (4) Dyslipidaemia (1; 25) enrolment to the study and longer duration of disease. Previous
studies have identified lower body mass index or weight to be gen-
Cyclosporin (16) Gastroesophageal reflux disease (1;
6.3) erally associated with better response to biologic treatment.11,14–­16
Raised creatinine (1; 6.3) However, age, duration of disease, baseline severity and previous

Hypertension (2; 12.5)

treatment have not been consistently found to be positively or neg-
atively associated with biologic treatment response in patient and
Dyslipidaemia (1; 6.3)
physician-­based assessment scores.11,14–­16
Hydroxyurea (2) Cytopenia (2; 100)
Longitudinal follow-­up and future interval analyses of the
Methotrexate (14) Nausea (1; 7.1)
SINGPSOR will allow improved statistical power to detect differences
Vomiting (1; 7.1)
in outcomes between biologic agents and conventional systemic
Liver fibrosis (1; 7.1)
agents for the treatment of psoriasis and assess the possibility of age
(B) Adverse events in those who received biologic therapy and duration of disease as potential confounders of treatment efficacy.
Adalimumab (21) None
Guselkumab (7) Transaminitis (1; 14.3) AU T H O R C O N T R I B U T I O N S
Infliximab (1) Transaminitis (1; 100) Dr Xuan Qi Koh: data collection, analysis, wrote the paper. Ms
Ixekizumab (13) Nausea (1; 7.7) Xiahong Zhao: data collection, analysis. Professor Bernett Lee: data
Secukinumab (8) Injection site reaction (1; 12.5) analysis, revision. Dr Eugene S.T. Tan: designed research study, data

Ustekinumab (25) Demyelination (1; 4) analysis and acquisition, wrote the paper. Dr Hazel H. Oon: designed
research study, data acquisition, wrote the paper. Professor Wei-­
Hepatitis B reactivation (1; 4)
Sheng Chong: designed research study.

AC K N O​W L E D
​ G E ​M E N T S
5 | CO N C LU S I O N S A N D PE R S PEC TI V E S The authors are grateful for the support of research coordinators
and support staff from NSC: Emily QY Tang, Mei Qi Ho, ZhiQing Lin,
The main limitation of our study is the short duration of follow-­up Joan Fung and Veron Lu.
and small sample size. This necessitated grouping all biologics into a
single group for analysis, thereby negating the possibility of compar- F U N D I N G I N FO R M AT I O N
ing baseline or follow-­up characteristics between different biologic This study is supported by a research grant from Johnson & Johnson
modalities. Although all biologics were grouped into a single group Pte Ltd and received approval by the National Healthcare Group
in our study for comparison against the other group treated with Research Data Oversight Committee under standing database ap-
conventional systemic immunomodulators, this should not be taken plication number NSC/2021–­0 0083.
as a suggestion that different biologics are simply interchangeable as
therapeutic options. C O N FL I C T O F I N T E R E S T S TAT E M E N T
Psoriasis was previously understood as a CD4+ T-­cell immune-­ HH Oon is a speaker, advisory board member and researcher for
mediated disease that predisposed by genetic and environmental fac- Galderma, Janssen and Novartis. She has also been a clinical investi-
tors and manifested by keratinocyte hyperplasia. Cyclosporin inhibits gator for Pfizer, as well as a speaker and advisory board member for
CD4+ T-­cell activation, whilst methotrexate exhibits general immuno- AbbVie, Eli Lilly and LEO Pharma.
modulatory and anti-­proliferative activity, and retinoids modulate epi-
dermal keratinocyte proliferation and differentiation. In recent years, DATA AVA I L A B I L I T Y S TAT E M E N T
greater understanding of the immunologic dysregulation in psoriasis The data that supports the findings of this study are available in the
has identified alterations in both innate and adaptive immune systems, supplementary material of this article.
TNF-­α, IL-­17, IL-­23, janus kinase and tyrosine kinase 2. Biologics are
proteins that can specifically target some of these immune media- ORCID
tors, thus potentially producing better treatment efficacy with lesser Xuan Qi Koh https://orcid.org/0000-0002-0594-5519
adverse reactions.8 Our results suggest that patients who received Hazel H. Oon https://orcid.org/0000-0001-7607-3124
biologic treatment showed a trend towards greater improvement in
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information can be found online in the
Supporting Information section at the end of this article.
Tables S1–­S2
How to cite this article: Koh XQ, Oon HH, Chong W-S, Lee
B, Zhao X, Tan EST. Clinical and patient-­reported outcomes
from the first 4 years of a Psoriasis Biologics Registry in
Singapore. Exp Dermatol. 2023;00:1-6. doi:10.1111/
exd.14910