7.
2
Pros and cons of oclacitinib therapy
W.S. Rosenkrantz1 (Chairperson) and A.S.
Bourgeois2 (Secretary)
1
Animal Dermatology Clinic, Tustin, CA, USA
2
Animal Dermatology Clinic, Milwaukie, OR, USA
Wayne Rosenkrantz (USA) opened the workshop by
explaining the use of a polling-based programme called
Turning Point Technology. This allows each individual
audience member to answer questions anonymously and
presents the collective results for discussion.
To demonstrate use, a general question was asked:
How familiar are you with Janus kinase (JAK) inhibitors?
1 Never heard of them (2%)
2 I have a very basic understanding (17%)
3 Only heard about them due to the Apoquel® release
(55%)
4 I am tired of hearing about them (26%)
Wayne Rosenkrantz recognized that most of the group
were familiar with JAK inhibitors. The JAK enzymes are
associated with cytokine receptors on the surface of cells.
The Janus domain is composed of two domains located
at the interface of the cell membrane. One domain stimu-
lates kinase activity and one downregulates activity.
These domains can induce a variety of immune reactions.
Inhibiting JAK can reduce immune responses, particularly
those associated with allergic reactions.
A schematic was shown illustrating the pathway of JAK
activation and the interactions of cytokines with the
receptors. Activation of JAK leads to phosphorylation of
receptor chains and translocation to the nucleus. JAK-
STAT (signal transducer and activator of transcription) inhi-
bitors function to block this pathway. Oclacitinib
(Apoquel®; Zoetis Inc., Parsippany, NJ, USA) inhibits pri-
marily JAK-1 and has minimal effect on JAK-3. At recom-
mended dosages there is no effect on JAK-2 or tyrosine
kinase. Oclacitinib’s primary mode of action in reducing
itching is inhibiting production of interleukin (IL)-31. How-
ever, production of other cytokines (IL-2, 4, 6 and 13) is
also affected. While the JAK-1 pathway is primarily
affected, when dosed at 0.6 mg/kg twice daily, the peak
concentration of the drug in some dogs may also inhibit
JAK-2 pathways. This may be why, in rare instances, ocla-
citinib-treated dogs may exhibit transient leukopenia and
neutropenia.
The audience was polled with a second question, How
would you classify your current usage of oclacitinib?
1 Have never used it (18%)
2 Treated 25–50 cases (37%)
192
3 Treated 50–100 cases (8%)
4 Treated 100–200 cases (15%)
5 Treated more than 200 cases (22%)
Wayne Rosenkrantz recognized that the attendees have
treated a significant number of cases. Only a small per-
centage of the audience had never used the drug and is
likely participating in the workshop to obtain more infor-
mation regarding how to use this drug.
The next question was How effective is oclacitinib in
your practice for controlling pruritus to an acceptable level
[using a definition of 50% reduction of the original pruritus
visual analogue scale (PVAS) scoring]?
1 <40% (3%)
2 40–50% (6%)
3 50–60% (2%)
4 60–70% (21%)
5 >70% (68%)
Wayne Rosenkrantz noted that participants are finding
good control of itching with use of oclacitinib when
defined as a reduction of 50% from the original PVAS
scoring.
The follow-up question was How effective is oclacitinib
in your practice for controlling pruritus to an acceptable
level using the definition of <2 on PVAS?
1 <40% (7%)
2 40–50% (0%)
3 50–60% (20%)
4 60–70% (27%)
5 >70% (46%)
Wayne Rosenkrantz expected a lower percentage of
complete control.
The floor was then opened to feedback and questions
from participants regarding clinical experience with oclaci-
tinib improving pruritus.
Sue Paterson (UK) mentioned that she often finds good
control of patient pruritus. However, she noted that
patients frequently experience a loss of control due to
Malassezia and bacterial overgrowth.
Valerie Fadok (USA) disclosed that she works for Zoetis
Inc. She believes a confounding factor is whether dogs
are on immunotherapy or not. In her experience, dogs on
concurrent immunotherapy have a better response to
oclacitinib.
Paul Bloom (USA) shared his clinic’s results in 444 cases.
There was a 22% failure rate defined as clients that did
not feel dogs achieved a normal level of pruritus. When
the dose was split throughout the day 1.5% of patients
© 2017 The Authors. Compilation © 2017 ESVD and ACVD

improved. Clinical improvement was also dependent on
the dose. If the higher dose of 0.6 mg/kg daily was used
there was better control compared to dogs at the lower
end of the dosage range (0.4 mg/kg daily).
Candace Sousa (USA) disclosed that she works for Zoe-
tis Inc. She stated that the majority of cases studied in the
USA were chronic atopic patients. This may be why suc-
cess rates in dermatology referral practices are lower than
in general practice. Acute or short-term use tends to show
better success rates than chronic use or when disease
has been present for several years.
Wayne Rosenkrantz stated that oclacitinib has a very
rapid onset of activity compared to corticosteroids and
that its effect is much more rapid than that of ciclosporin.
There are several references supporting oclacitinib being
highly effective in treating pruritus. The Cosgrove study1
showed a greater than 50% reduction in pruritus within
90 days in 63.4% of cases. The range of dogs achieving a
PVAS <2 was 38.5–48.5%. There was also a dramatic
improvement in quality of life in many cases.
Wayne Rosenkrantz went on to discuss details from a
random selection of 175 cases from an oclacitinib-treated
population of more than 1000 cases at the Animal Derma-
tology Clinic’s Tustin (California, USA) location (ADC-T).
These cases had been on oclacitinib for a minimum of 6
months and did not include cases that dropped out due to
perceived early failure or inconsistent use.
The study was a retrospective evaluation. The results
showed that 56/175 (32%) had an excellent response,
with owners considering treated dogs to be ‘normal’.
Some of these cases were on modified dosing protocols
(such as 0.3 mg/kg twice daily). Some cases 11/56
(19.6%) were on concurrent immunotherapy. Moderate
control was seen in 102/175 (58.3%) cases. Some
patients in this group received modified or increased dose
protocols. Concurrent corticosteroids with oclacitinib
were used in 23/102 (22.5%) of the moderate respon-
ders. Within the moderate responder group, 24/102
(23.5%) were on concurrent immunotherapy. A smaller
number of cases, 16/175 (9.1%), had limited to no
response to oclacitinib and were transitioned to other
treatment options after 6 months of treatment.
Photos were shown of dogs with various responses to
Apoquel®.
The recommended dose of oclacitinib (0.4–0.6 mg/kg
twice daily for 14 days and then reduced to once daily)
was discussed. Options for dose adjustments were also
further discussed. This led to a question to the partici-
pants regarding dosage adjustments: When response is
limited, what type of dose adjustments do you make?
1 No adjustments; follow the recommended label dos-
ing and give time (26%)
2 Divide daily dose into twice daily 25% of the time
(19%)
3 Divide daily dose into twice daily 50% of the time
(24%)
4 Need to keep at induction dose twice daily >10% of
the time (19%)
5 Other modifications (12%)
Pros and cons of oclacitinib therapy
Wayne Rosenkrantz recognized that many people use
modified dosages and protocols. Further discussion on
this followed.
Margreet Vroom (The Netherlands) stated that it is not
always necessary to start with twice-daily oclacitinib dos-
ing even for induction. She often starts with once-daily
dosing initially and still sees a rapid response. She
increases to twice-daily dosing after a few days if once
daily is not effective. Owners also often make dose
adjustments on their own, which can be worrisome.
Sophie Gilbert (Canada) mentioned that changing the
time of day the drug is given can also be beneficial and
should correspond to the time of the day that the dog
exhibits the most intense pruritus. In addition, if patients
are at the lower end of the dosing (0.4 mg/kg), increasing
to the higher end (0.6 mg/kg) can help. Making changes
may be limited by the availability of tablet sizes.
Jerome Ngo (Belgium) stated owners do not seem satis-
fied when dosing is changed from twice daily to once
daily. He often starts at once-daily dosing to avoid this.
Robert Dixon (Australia) mentioned some dogs will do
better receiving a higher dose in the morning and a lower
dose in the evening. This could be due to the short half-
life of the drug. This type of modification can be used to
avoid using the full 0.6 mg/kg twice-daily dosing beyond
the 14-day induction.
Wayne Rosenkrantz stated that he likes to try to start at
0.6 mg/kg twice daily for his patients and typically calcu-
lates the dosing to make sure patients start at the higher
end of the dosing recommendations. He asked if the
group uses the dosing chart or if they actually calculate
the dosage based on body weight to get a more exact
mg/kg dosing. About a third of the attendees stated they
strictly use the provided dosing chart when starting dogs
on oclacitinib. Approximately two-thirds calculate the
dose themselves.
Ed Rosser (USA) stated he has tried many different modi-
fications but in about 10% of his cases he cannot reduce
below 0.6 mg/kg twice-daily dosing for maintenance.
Wayne Rosenkrantz next asked the following question:
What type of dose adjustments do you make in a patient
with a good response to oclacitinib?
1 Reduce to every other day dosing in <5% of the
cases (48%)
2 Reduce to every other day dosing in 5–10% of the
cases (25%)
3 Reduce to every other day dosing in 10–15% of the
cases (5%)
4 Give only as needed (22%)
It appears that only a limited percentage of cases can
successfully taper to dosing every other day. The audi-
ence was invited to share experiences regarding dose
reductions.
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Claudia Nett (Switzerland) only uses the oclacitinib as
needed in patients. She finds there are dogs in which you
can give the drug for 3–4 days in a row and then just use
as needed.
Valerie Fadok mentioned that she gives oclacitinib as
needed more in patients that are on immunotherapy. She
uses the drug only when patients flare when they are on
concurrent immunotherapy.
Wayne Rosenkrantz discussed his experience of dosing
and frequency in 175 cases evaluated in a retrospective
study at ADC-T: 77/175 (48%) could be maintained on
once-daily dosing; 43/175 (24.5%) were maintained by
splitting the 0.4–0.6 mg/kg dose into twice-daily incre-
ments; 19/175 (10.8%) received 0.4–0.6 mg/kg dosing in
the morning and 0.2–0.3 mg/kg dosing in the evening;
and 13/175 (7.4%) had to be maintained at 0.4–0.6 mg/kg
twice daily. The latter is obviously off label and may
increase the risk of side effects.
The next two questions related to comments that ocla-
citinib loses effectiveness over time. First, How often do
you see this?
1 Not seen (31%)
2 10% of cases (26%)
3 20% of cases (26%)
4 30% of cases (6%)
5 Other (11%)
Second, In those cases where it (oclacitinib) has lost its
effectiveness, why did it occur?
1 Compliance (2%)
2 Drug just quit working (12%)
3 Pyoderma (24%)
4 Malassezia (5%)
5 Fleas (4%)
6 Food allergy (5%)
7 Other (48%)
Wayne Rosenkrantz recognized that most of the audi-
ence agree that the drug did not just stop working; in
most cases, some other confounding or flare factor is pre-
sent. A picture was shown of a dog that had developed
pyoderma while on Apoquel®. The pyoderma created the
lack of control.
Sue Paterson asked for the audience’s opinions regarding
discontinuing oclacitinib while treating pyoderma.
Jackie Campbell (USA) stated it was important to man-
age all factors contributing to skin disease in a patient,
including pyoderma. Adding antibiotics while continuing
to treat the allergies with oclacitinib will help the patient.
There are also certain times of the year when oclacitinib is
needed more than others.
Ursula Mayer (Germany) agreed that successful treat-
ment of a dog with allergies goes beyond just treating the
pruritus. It includes reducing frequency of infections. If
infections are continuing in allergy patients, then their
194
allergies are not fully controlled with oclacitinib alone.
Additional anti-allergic therapies may be needed.
Alberto Cordero (Mexico) mentioned that he does not
think ear disease responds as well to oclacitinib when
compared to other available medications such as corticos-
teroids.
Wayne Rosenkrantz stated the next topic would include
adverse events and then asked a series of questions com-
paring oclacitinib to other therapies in regards to adverse
events.
First, What is your perception of adverse events with
oclacitinib compared to ciclosporin?
1 It is very low, less than ciclosporin (86%)
2 It is similar to ciclosporin (11%)
3 It is higher than ciclosporin (3%)
This is an expected finding due to the higher incidence
of gastrointestinal side effects associated with ciclos-
porin.
Second, What is your perception of adverse events
with oclacitinib compared to glucocorticoids?
1 It is very low, less than steroids (100%)
2 It is similar to steroids (0%)
3 It is higher than steroids (0%)
Finally, What is your perception of adverse events with
oclacitinib compared to allergen-specific immunotherapy
(ASIT)?
1 It is very low, less than ASIT (18%)
2 It is similar to ASIT (50%)
3 It is higher than ASIT (32%)
Wayne Rosenkrantz stated that it is a bit unusual to see
such high numbers reporting adverse events in ASIT,
which is generally considered the safest of all options.
Regarding oclacitinib, when you look at the current litera-
ture the reports of adverse events are relatively low.
Looking at the previously mentioned Cosgrove study,1
urinary tract infections, pyoderma, otitis, weight gain,
vomiting and diarrhoea were the most commonly noted
adverse events. Less common adverse events reported
in the literature or anecdotally include pneumonia, inter-
digital cysts, demodicosis, lethargy, tremors, haematolo-
gical abnormalities, neoplasia, seizures and aggression.
Next, questions were used to survey the group on inci-
dence of some of these adverse events.
What incidence of cystitis are you noticing?
1 Do not routinely check (53%)
2 <5% of cases (37%)
3 5–10% of cases (5%)
4 10–15% (0%)
5 >15% (5%)
Catherine Outerbridge (USA) wanted to further discuss
reports of weight gain and reasons for it. She was won-
dering if it could be associated with the dogs that start out

extremely pruritic prior to using oclacitinib. Once the pruri-
tus is improved, patients are not moving as much due to
lack of scratching. She felt you could see weight gain in
many of these patients no matter which therapy is used
as long as the pruritus is controlled.
Wayne Rosenkrantz replied he does not necessarily
think weight gain is related to reduced pruritic activity and
plans to discuss other theories later in the workshop.
Ed Rosser mentioned complaints from clients regarding
polyphagia.
Wayne Rosenkrantz asked participants to hold discus-
sion of weight gain until after the discussion on cystitis
and some of the other adverse effects.
Rod Rosychuk (USA) reported that a study of 43 dogs
from Colorado State University on oclacitinib did not find
any cases with cystitis.
Paul Bloom was curious about the definition of cystitis
everybody was using. Specifically, he asked whether the
patients were symptomatic or not when the term cystitis
was being used.
Wayne Rosenkrantz stated that most doctors in his prac-
tices collect complete blood count (CBC), serum chemis-
try (CHEM) and urinalysis (UA) prior to starting therapy. Of
the 175 cases followed in the ADC-T study, 11 dogs
(6.3%) were diagnosed with cystitis. The presence of bac-
teria with white blood cells was the criterion used to diag-
nose cystitis. In addition, 24/175 (13.7%) developed 2+
proteinuria and 10/175 (5.7%) developed 3+ proteinuria.
The dogs with 3+ proteinuria had a urine protein/creati-
nine (UPC) ratio performed and 3/10 (30%) of these cases
had an elevated UPC ratio. Of these, one owner decided
to discontinue therapy with oclacitinib and two owners
decided to continue. All 10 dogs with 3+ proteinuria had
negative urine cultures.
Sue Paterson commented that intertriginous dermatitis
around the vulvar fold and preputial fold is a factor she
believes is associated with a higher incidence of
bacteriuria.
Paul Bloom was curious if the 6.3% of cystitis cases in
the ADC-T study were symptomatic.
Wayne Rosenkrantz answered that some were; how-
ever, not all cases exhibited frequent urination or a stron-
ger odour to their urine.
Paul Bloom wanted to know if there was follow-up with
the cases mentioned having 3+ proteinuria in the ADC-T
study.
Wayne Rosenkrantz stated cases were referred back to
their primary care veterinarian and enalapril was pre-
scribed for blood pressure issues in some cases. Only
one-third of dogs with the proteinuria stayed on Apoquel®
and the UPC ratio remained stable. He asked if anybody
Pros and cons of oclacitinib therapy
else had seen proteinuria associated with oclacitinib
treatment.
Rod Rosychuk mentioned proteinuria was noted in some
of the 43 cases at Colorado State University. However,
one of the cases had lymphoma.
Valerie Fadok asked the internists how a 6% rate of
occurrence would compare to normal age-matched dogs.
Rod Rosychuk stated it would be right where you would
expect it.
Wayne Rosenkrantz then discussed the occurrence of
pyoderma. In the same case review at ADC-T, 91/175
(52%) were treated two or more times for pyoderma dur-
ing treatment with oclacitinib. It was recognized that 20/
91 (21.9%) had a previous history of recurrent pyoderma.
It is difficult to know whether oclacitinib contributed to
the high incidence of pyoderma. Occurrence of otitis was
also looked at and it also seemed high but no exact num-
bers were presented. He asked the audience their general
impression of oclacitinib causing otitis.
Rod Rosychuk mentioned that the ears are examined on
all patients at Colorado State University. He does not feel
that cases with recurrent otitis are well controlled on ocla-
citinib. Concurrent topical therapy is often used for these
cases.
Jon Plant (USA) commented that we need to be careful
when we retrospectively look at some of the newer drugs
because we often follow these cases much more closely
compared to patients treated with other medications that
have been available for years.
Wayne Rosenkrantz mentioned that it is hard to
determine oclacitinib’s ability to control otitis since this is
such a common secondary issue with atopic dermatitis.
However, it does not appear to work as well as other anti-
inflammatory drugs for otitis cases.
Catherine Outerbridge agreed. She still uses topical cor-
ticosteroids for management of otitis in addition to oclaci-
tinib. She believes oclacitinib is more of an antipruritic
agent than an anti-inflammatory one.
Brett Wildermuth (Germany) has mixed opinions on the
control of otitis with oclacitinib. Stenotic ears do not
seem to improve as quickly with oclacitinib as with
corticosteroids. However, some Labrador retrievers do
seem to have less frequent episodes of Malassezia otitis
while on oclacitinib.
Wayne Rosenkrantz agreed that he would use corticos-
teroids preferentially for proliferative ear disease.
Ed Rosser feels that pyoderma can worsen when oclaciti-
nib is used concurrently for pruritus. Also, he has seen
side effects such as borborgymus, bloating and abdom-
inal discomfort in patients with a history of gastrointest-
inal disease.
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Ursula Mayer commented that she does not think oclaci-
tinib works well for treating interdigital granulomas.
Wayne Rosenkrantz agreed and stated that this was
confirmed in some of the earlier studies and also in his
clinical cases.
Margreet Vroom stated that she has two cases that
became quite ill (lethargy, diarrhoea, etc.) on oclacitinib.
These clinical signs resolved when the drug was
discontinued and returned when the drug was
restarted.
Paul Bloom has had dogs with a history of inflammatory
bowel disease resolve their gastrointestinal disease when
on oclacitinib.
Wayne Rosenkrantz mentioned that liver enzyme eleva-
tions were seen in his cases at ADC-T, with 47/175
(26.8%) having alkaline phosphatase (ALP) elevations.
Most elevations were fairly mild. Some 23/175 (13.1%) of
cases were on concurrent oral glucocorticoids and 12/23
(52.5%) of those cases had ALP elevations. When just
evaluating the 47 cases of ALP elevations, 35 (74.4%) of
the ALP elevations were not related to systemic steroid
use. Also, 6/175 (3.4%) had alanine transaminase (ALT)
elevations.
He reported that Allison Kirby at Animal Dermatology
Clinic’s Marina Del Rey location (California, USA) has had
three dogs treated with oclacitinib diagnosed with biliary
mucoceles. These patients started with elevated ALT
and ALP values and then became extremely ill. All three
cases were confirmed through abdominal ultrasound
and had surgery. These cases have been reported to
Zoetis Inc.
Many audience members agreed that they have seen
liver enzyme elevations from oclacitinib. Nobody in the
audience had seen a biliary mucocele as a possible side
effect.
Rod Rosychuk asked if the dosing regimen was evalu-
ated for these cases.
Wayne Rosenkrantz replied that there did not seem to
be a correlation between the high dose (0.6 mg/kg daily)
versus the lower end of the range (0.4 mg/kg daily).
Ed Rosser commented that he has five patients that have
been monitored with ALP elevations from oclacitinib for
over a year. Four of the cases had ALP in the 400 µg/dL
range. One case had an ALP in the 900 µg/dL range. He
monitors laboratory parameters every 3 months rather
than every 6 months in these patients. These patients
have no evidence of Cushing’s disease. However, when
an ALP panel was evaluated at the University of Illinois,
90% was the steroid-induced isoform.
Catherine Outerbridge was curious of the breed repre-
sentations for the three previously diagnosed dogs with
biliary mucocele. There are certain breeds that are predis-
posed.
196
Wayne Rosenkrantz did not have that information readily
available but could easily look it up.
The next question was How many cases of demodico-
sis have you seen related to oclacitinib?
1 1 (69%)
2 2–3 (25%)
3 4–5 (0%)
4 5–10 (3%)
5 Greater than 10 (3%)
Candace Sousa mentioned there was no option to select
zero cases in the above question.
Wayne Rosenkrantz recognized that it was an error on
his part to not include zero. Attendees were asked to raise
their hand if they had not seen any cases of demodicosis
related to oclacitinib. Approximately 12/65 (18.5%) people
raised their hands. In the ADC-T population, there were 6/
175 (3.4%) that were diagnosed with demodicosis. How-
ever, 3/6 (50%) of those cases were treated with afoxola-
ner (Nexgard®; Merial Inc., Duluth, GA, USA) and
continued with their oclacitinib, and the demodicosis has
been in remission.
He shared a case example of one of these cases that
continued on oclacitinib with afoxolaner. He asked if the
audience had any comments.
Brett Wildermuth asked about the case example and if
he was receiving once-daily or twice-daily dosing of oclaci-
tinib.
Wayne Rosenkrantz stated that the case example was
on once-daily dosing but was not sure of the exact dose
although he typically tries to use the higher-end dosing at
0.6 mg/kg/day.
Margreet Vroom reported she uses oclacitinib in dogs
that are pruritic even if demodectic mites are present.
Wayne Rosenkrantz asked how she was treating the
Demodex.
Margreet Vroom stated that she treated with either afox-
olaner or fluralaner (Bravecto®; Merck Animal Health,
Summit, NJ, USA). She mentioned that many dogs
develop demodicosis, so we cannot necessarily implicate
oclacitinib as the cause.
Wayne Rosenkrantz recognized that the number of
Demodex cases is low. However, it should be something
we are aware of and should screen cases when lesions
are compatible.
Ed Rosser stated that dogs he has seen with demodico-
sis from oclacitinib tend to be adult-onset and not juve-
nile.
Sue Paterson mentioned that she often starts patients
on oclacitinib and fluralaner concurrently to prevent demo-
dicosis.

Wayne Rosenkrantz then asked about weight gain.
Noticeable weight gain is seen in what percentage of your
cases?
1 None (30%)
2 <5% (45%)
3 5–10% (17%)
4 10–20% (5%)
5 >20% (3%)
Based on previous studies, weight gain seemed to
occur more the longer dogs were on oclacitinib. In most
studies a small percentage of treated dogs are affected
(4%). Another study by Little and coworkers2 reported
1.19% of dogs on ciclosporin and 3.35% of dogs on ocla-
citinib with weight gain.
In the Cosgrove study,1 10% average weight gain was
seen; this is higher than other studies. Wayne Rosenk-
rantz has been quite interested in weight gain and has
been looking into possible explanations. In most of his
cases the dogs did not appear to be polyphagic. In the
175 cases evaluated at the ADC-T there was an average
weight gain of 6.8%.
One theory discussed is the possibility of adipose tis-
sue being affected by JAK-STAT inhibitors. There are doz-
ens of adipose tissue cytokines and some use JAK
receptors. JAK-STAT transcription factors impact various
areas of adipocyte metabolism including insulin action,
modulation of lipid stores, leptin levels and glucose home-
ostasis. Leptin regulates energy balance, inhibiting hun-
ger. The JAK-STAT pathway is also involved in deposition
of brown adipose tissue.
A study3 revealed that some mice have a mutation in
the leptin receptor gene that prevents activation of STAT-
3; these mice become obese.
Valerie Fadok stated some studies have shown that
blocking IL-6 leads to weight gain. This is being evaluated
in human oncology patients. She agreed there are many
adipose cytokines that use the JAK-STAT pathway.
Wayne Rosenkrantz next initiated a discussion regarding
oclacitinib and neoplasia by asking the group What are
you telling your clients regarding oclacitinib and neopla-
sia?
1 I do not tell them anything (20%)
2 There appears to be no known association with neo-
plasia (31%)
3 It is possible that it could create neoplasia (13%)
4 It is possible that it could exacerbate neoplasia
(22%)
5 We just do not know so I would be careful using it
(11%)
6 I would not use it in my dog (3%)
He went on to say that when reviewing the literature
regarding JAK-STAT inhibitors and neoplasia in human
medicine he found many reports showing benefits of
using these drugs to treat neoplasia but very little discus-
sion regarding it as a risk factor for neoplasia. One study4
made the following summary statement, ‘As Janus
Pros and cons of oclacitinib therapy
kinase inhibitors alter the immune response they increase
the risk of serious infections. There is a possibility they
may also increase the risk of cancer.’
Another study5 evaluated tofacitinib, a JAK-STAT inhibi-
tor used in humans for rheumatoid arthritis. This study
evaluated 5671 cases and there was no increased risk or
incidence of neoplasia in people treated with tofacitinib
compared to other forms of therapy. The standardized
incidence ratios for all malignancies and selected malig-
nancies were within the expected range of patients with
moderate-to-severe rheumatoid arthritis.
There has been some concern about papillomas asso-
ciated with oclacitinib in dogs. Some members of the
audience agreed they have seen this. Papillomas in pivotal
laboratory studies in healthy dogs were not dose-related
and were seen at one-, three- and five-times dosing.
Data shared in a previously sponsored Zoetis Inc. webi-
nar by Cheryl London from the Ohio State University
(USA) reviewed neoplasia cases from continuation stu-
dies. There were 239 dogs treated with oclacitinib for a
mean of 372 days (range 1–610 days); of these, 16 dogs
(6.6%), with an average age of 9 years, developed sus-
pected or confirmed neoplasia. Twelve different types of
tumour, including two grade II mast cell tumours (MCTs),
were seen. Her conclusion was that the neoplasia rates in
oclacitinib-treated dogs were not increased compared to
an age-matched population.
Craig Griffin reviewed 179 cases seen at Animal Der-
matology Clinic’s San Diego location and four dogs (2.2%)
developed masses that were not identified, three (1.7%)
developed lymphoma and one (0.55%) developed pros-
tate cancer. Again, these numbers are quite low and were
seen in elderly dogs (range 8–16 years old).
Of the 175 cases at ADC-T, one dog (0.57%) developed
a retroperitoneal hemangiosarcoma, one (0.57%) devel-
oped nerve sheath tumour, one (0.57%) developed a
grade I MCT, one (0.57%) developed an undifferentiated
lymphohistiocytic tumour, one (0.57%) developed lym-
phoma, one (0.57%) developed mammary carcinoma,
one (0.57%) developed a ceruminous gland adenocarci-
noma, one (0.57%) developed an adrenal adenoma and
four dogs (2.28%) developed histiocytomas.
Wayne Rosencrantz concluded this topic discussion
with some summary points given by Cheryl London from
the Zoetis Inc. webinar: (1) when you review the inci-
dence of neoplasia in the general population of dogs, can-
cer is the leading cause of death in dogs and 1/4 (25%)
die of cancer, (2) the highest incidence is seen in dogs
between 6 and 12 years of age with a peak of 10 years,
(3) many breeds of dogs that are predisposed to neoplasia
are also predisposed to atopic dermatitis and (4) con-
trolled studies to date do not support a direct association
with oclacitinib.
Despite this, there remain anecdotal reports on oncol-
ogy and veterinary dermatology list serves regarding the
concern of an increased risk for neoplasia.
Wayne Rosenkrantz next wanted to get feedback from
the group regarding the types of monitoring of oclacitinib
cases. Specifically, he does CBC, CHEM and UA prior to
starting medication, 3 months after and then every 6
months on maintenance. There was some consensus on
197
Workshops
similar monitoring from the group, although a small num-
ber of attendees did no monitoring.
The floor was then opened for final comments and
feedback.
Ursula Mayer asked about experiences of oclacitinib use
in cats.
Wayne Rosenkrantz stated he has treated 5 cats with
oclacitinib at 1 mg/kg twice daily. One of the five had a
complete response and two had a partial response. The
partial responders also needed concurrent lower dose cor-
ticosteroids.
Many in the audience mentioned that their experiences
were varied.
Ursula Mayer reported that she had three cats that had
failed previous therapies but which had good results with
oclacitinib.
Margreet Vroom had one of four cats respond well to
oclacitinib.
Otto Fischer (Austria) was curious about combination
therapy with oclacitinib and other medications.
Wayne Rosenkrantz mentioned several dogs that were
on concurrent corticosteroids with oclacitinib in the ADC-
T study were controlled with low doses of both medica-
tions. He has not noticed complications from using low
doses of both medications, especially if just a short-term
duration.
Catherine Outerbridge stated it is important to confirm
no secondary pyoderma is present. She has experience
with one diabetic cat that could be controlled with a lower
dose of triamcinolone by using concurrent oclacitinib.
Otto Fischer asked if the audience would prefer oclaciti-
nib or ciclosporin as first-line treatment. Due to access in
his country, he has only had experience with oclacitinib
for 2 weeks.
Wayne Rosenkrantz mentioned oclacitinib is excellent
for acute flares in atopic dogs. Immunotherapy is still his
drug of choice for long-term management. Immunother-
apy is the safest therapy that can be used and has bene-
fits even if it just reduces the dose of other
immunosuppressive drugs.
198
Jerome Ngo asked about loss of treatment efficacy over
time. He was wondering if it could be due to the accumu-
lation of IL-31 due to blocking of the receptor.
Wayne Rosenkrantz mentioned that other complications
such as pyoderma and other flare factors seem to be
more of a problem. He questioned whether blocking IL-31
could possibly cause a rebound effect. He asked for opi-
nions from members of the audience.
Valerie Fadok and Candace Sousa were not aware of
data that supported an accumulation of IL-31.
Catherine Outerbridge thought that this could be possi-
ble. When owners stop oclacitinib on their own they often
report that the pruritus seems worse than before treat-
ment. Owners may have forgotten how severe the aller-
gies were or the allergies may be getting worse since the
treatment is just blocking the symptom of itching. Aller-
gies do tend to get worse over time in some individuals.
This is a reason why immunotherapy is still essential in
the treatment of atopic dermatitis.
Candace Sousa mentioned a presentation that was going
to be given by Rosanna Marsella at the current World
Congress reporting that oclacitinib may have the ability to
increase time to new sensitizations in atopic dogs.6
Wayne Rosenkrantz thanked everyone for their feed-
back and for attending the workshop.
References
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171–179.
2. Little PR, King VL, Davis KR et al. A blinded, randomized clinical
trial comparing the efficacy and safety of oclacitinib and ciclos-
porin for the control of atopic dermatitis in client-owned dogs. Vet
Dermatol 2015; 26: 23–30.
3. Wang B, Chandrasekera C, Pippin JJ. Leptin- and leptin receptor-
deficient rodent models: relevance for human type 2 diabetes.
Curr Diabetes Rev 2014; 10, 131–145.
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