A Retrospective Case Series Reporting the Clinical Efficacy and Adverse Events of Oclacitinib Administration for Skin Disease in 238 Cats

ABSTRACT

Background

Off‐label oclacitinib use for feline dermatoses management is increasing despite the paucity of data regarding optimal dose and adverse events (AEs).

Objective

Review AEs, clinical efficacy, and dose regimens in cats prescribed oclacitinib.

Materials and Methods

Retrospective case series of 238 privately owned cats prescribed oclacitinib for dermatological disease. Signalment, history, laboratory abnormalities, oclacitinib dosage (mg/kg/day), treatment duration and AEs using a modified Naranjo Adverse Drug Reaction Probability Scale were retrieved from medical records spanning August 2014 to May 2024. Clinical efficacy was estimated using a pruritus Visual Analogue Scale and medical record lesional descriptions; categorised as complete, partial or no response.

Results

The mean (x̄) initial dosage prescribed was 1.89 mg/kg/day. Monotherapy controlled clinical signs in 140 of 238 cats (59%), including 83 of 140 cats (59%) on twice daily (x̄ = 1.85 mg/kg/day) and 57 of 140 cats (41%) on once daily administration (x̄ = 1.05 mg/kg/day). The median treatment duration was 271.5 days (range 1 day–7.5 years). Main diagnoses successfully managed included feline atopic skin syndrome (61%) and pemphigus foliaceus (29%). Thirty‐three ‘definite’ or ‘probable’ AEs were observed in 32 of 238 cats including: neutropaenia 6.3% (n = 15), gastrointestinal 4% (n = 9), lethargy 1.7% (n = 4), infection 0.8% (n = 2), hyperactivity 0.4% (n = 1), elevated alanine transaminase 0.4% (n = 1) and elevated creatinine 0.4% (n = 1).

Conclusions and Clinical Relevance

Off‐label oclacitinib administration in cats appeared to be well‐tolerated and effective with AEs typically mild, responsive to dose reduction, and similar to those reported in dogs.

1. Introduction

The most common primary dermatological condition diagnosed in cats is feline atopic skin syndrome (FASS), an inflammatory and pruritic disorder manifested by a spectrum of reaction patterns [1, 2]. Management of FASS and other immune‐mediated dermatoses often requires long‐term systemic immunosuppressants such as ciclosporin and corticosteroids [3]. Usage of these medications can, however, be limited by adverse health events or difficulty with administration.

Up to 66% of cats treated with ciclosporin experience adverse events (AEs) such as vomiting or diarrhoea, ptyalism, weight loss, long‐standing anorexia and gingival hyperplasia [4, 5, 6]. Moreover, ≤ 21% of owners report difficulty with administration, and approximately 25% of cats fail to respond to treatment [7]. Chronic corticosteroid use also can be limited by adverse effects including the development of steroid‐induced congestive heart failure (0.82%) and diabetes mellitus (3.8%–9.7%) [8, 9, 10, 11, 12]. Given these concerns, alternative oral antipruritic and anti‐inflammatory therapeutic options are needed for cats.

Oclacitinib maleate is a Janus kinase (JAK) inhibitor approved for canine atopic dermatitis yet used off‐label to manage other canine immune‐mediated dermatoses [13, 14, 15, 16, 17, 18, 19]. It is typically well‐tolerated in dogs and most AEs are mild and self‐limiting. Haematological abnormalities are uncommon and include a reversible, dose‐related neutropaenia and mild increases in serum cholesterol [13, 14, 20, 21, 22, 23].

The favourable safety profile of oclacitinib and proven efficacy in dogs has prompted interest in its off‐label use in cats. Previously published feline case series suggest that it is generally well‐tolerated and most effective when administered twice daily and at increased doses as compared with dogs [24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35], yet optimal therapeutic dosing and safety recommendations have not been established. The current feline literature is largely restricted to single case reports or small, short‐term studies limited to 28 days, with the exception of a more recent retrospective series [31].

Reported AEs also have been sporadic and variable in severity, including: gastrointestinal (GI) signs, lymphadenopathy, mild elevations in creatinine or blood urea nitrogen (BUN), increased alanine aminotransferase (ALT), thrombocytopaenia and neutropaenia, plus one fatal case of toxoplasmosis in a feline immunodeficiency virus (FIV)‐positive cat receiving oclacitinib [27, 29, 36]. A recent communication [37] cited the rising incidence of acute renal toxicity in cats and dogs following ingestion of chewable oclacitinib, at dosages exceeding 12 mg/kg. These potentially life‐threatening overdose risks and inconsistent dosing recommendations highlight the need for comprehensive studies assessing long‐term safety and AE causality; additionally, standardised dosing guidelines for both FASS and other feline dermatoses are lacking.

The primary aim of this retrospective case series was to describe AEs in cats with skin disease receiving oclacitinib. The secondary aim was to provide a review of the diagnoses, dosing regimen, and clinical efficacy when available.

2. Materials and Methods

Electronic medical records of privately‐owned cats treated at two specialty veterinary dermatology facilities containing the search terms ‘oclacitinib’ or ‘Apoquel’ were retrospectively analysed from August 2014 to May 2024. Information recorded included: signalment, history, lifestyle (including diet, outdoor access and exposure to rodents), feline leukaemia virus (FeLV) and FIV status, laboratory abnormalities, details regarding oclacitinib use (duration, dosage, rationale for discontinuation) and potential AEs.

Feline patients with skin disease were required to have been prescribed oclacitinib (Apoquel; Zoetis) by a board‐certified referral clinician or dermatology resident. The use of all concurrent medications was allowed, including supplements, flea and tick prevention, allergen‐specific immunotherapy, other immunomodulatory drugs and any other oral, topical or inhaled agents. Exclusion criteria included incomplete medical records, inadequate follow‐up or owner confirmation that oclacitinib was never administered.

In order to qualify as an AE for review, the event must have occurred while the patient was receiving oclacitinib and the outcome was documented. A modified version of the Naranjo Adverse Drug Reaction Probability Scale originally created to assess ciclosporin AEs in cats [5, 38] was revised to include haematological abnormalities that resulted in a decrease or discontinuation of oclacitinib (Table 1). All potential AEs were classified as either ‘definite’, ‘probable’, ‘possible’ or ‘doubtful’. The new adaptation focused predominantly on body systems previously identified to have abnormalities following oclacitinib use (liver, kidney and neutrophil counts) [25, 27, 29]. Definitions for normal haematological reference ranges were based on both a consensus document from the Veterinary Cooperative Oncology Group as well as the International Renal Interest Society [39, 40]. The events were collectively reviewed by three clinicians, including two board‐certified referral clinicians and one veterinary dermatology resident, to establish agreement.

TABLE 1.

Adapted Naranjo Adverse Drug Reaction Probability Scale for review of potential clinical and haematological adverse events (AEs) in cats [5, 38].

Adverse drug reaction causality assessment
Definite	Recognised response to medication Reasonable temporal sequence Continuous improvement of event or laboratory test abnormality following dose reduction or withdrawal Repeatable adverse event upon re‐exposure
Probable	Recognised response to medication Reasonable temporal sequence Continuous improvement of event or laboratory test abnormality following dose reduction or withdrawal No re‐exposure
Possible	Reasonable temporal sequence Could be related to drug yet also could be explained by concurrent disease, blood artefact or other therapeutic agents Improvement was not documented because intervention was either: (i) not attempted or (ii) lacked follow up to draw conclusions
Doubtful	Did not meet the above criteria Likely to be related to factors other than drug administration Improved or normalised without intervention

Efficacy was estimated using pruritus Visual Analogue Scale (PVAS) [41] scores (validated in dogs only) and lesional descriptions documented in the medical record. Oclacitinib was considered to have a positive therapeutic response when an improvement in pruritus and/or lesions was observed as compared to pretreatment, and the clinician felt the improvement was sufficient to continue therapy.

Responses were further categorised as complete, partial or no response (NR). A complete response (CR) was defined as a cat on oclacitinib monotherapy with documentation of both lesion and pruritus control. Lesion control required the regression of active skin lesions without new lesion formation, and pruritus control was defined as a PVAS of ≤ 2. When a PVAS score was unavailable, client‐reporting of minimal pruritus was considered an acceptable substitute. A partial response (PR) was defined as a ≥ 50% improvement in pruritus or lesion severity. If the cat required additional long‐term anti‐inflammatory or antipruritic oral therapies, they were considered a PR, provided that the concurrent medications could be reduced as compared to pre‐oclacitinib use. Cats with minimal to no improvement in pruritus and/or lesions within 5 weeks as judged by the clinician were categorised as NR.

3. Results

3.1. Animals

Medical records from 326 cats were reviewed and 88 cats were excluded owing to: incomplete medical records (n = 55), oclacitinib prescribed before referral (n = 19), oclacitinib prescribed and never administered (n = 12) or duplicate patient records (n = 2). A total of 238 cats met the inclusion criteria.

The demographic data is summarised in Table 2. The average age at oclacitinib initiation was 7.4 years old (range 0.4–21.5 years). The primary diagnosis for each cat in the study included: 112 of 238 cats (47%) FASS sensu lato (no elimination diet performed), 98 of 238 cats (41%) FASS sensu stricto (pruritus failed to respond to elimination diet), six of 238 cats (3%) FASS with concurrent food allergy and 17 of 238 cats (7%) with pemphigus foliaceus (PF). One cat (0.4%) was diagnosed in each of the following categories: idiopathic ulcerative dermatitis, plasma cell pododermatitis (PCP), proliferative and necrotising otitis externa (PNOE) and cutaneous sterile pyogranuloma/granuloma syndrome (SPGS); additionally, there was one case of an unspecified inflammatory dermatosis.

TABLE 2.

Demographic characteristics of cats receiving oclacitinib (n = 238).

Demographic characteristics
Age (years)	Mean	7.4
	Range	0.4–21.5
Sex (n)	Male intact	1
	Male neutered	111
	Female intact	1
	Female neutered	125
Most represented breeds (n)	Domestic short hair	167
	Domestic medium hair	21
	Domestic long hair	20
	Siamese	6
	Ragdoll	3
	Bengal	3
	Persian	3
	Maine coon	2
	Other	13
Lifestyle (n)	Indoor only	218
	Indoor/outdoor	13
	Unspecified	7
Primary disease (n [%])	FASS sensu lato	112 (47%)
	FASS sensu stricto	98 (41%)
	FASS with food allergy	6 (3%)
	Pemphigus foliaceus	17 (7%)
	Cutaneous sterile pyogranuloma/granuloma syndrome	1 (0.4%)
	Idiopathic ulcerative dermatitis	1 (0.4%)
	Plasma cell pododermatitis	1 (0.4%)
	Proliferative and necrotising otitis externa	1 (0.4%)
	Unspecified inflammatory dermatosis	1 (0.4%)

Abbreviation: FASS, feline atopic skin syndrome.

Feline viral testing was available in 163 of 238 cats (68%) and one cat was FIV‐positive. Lifestyle was documented with 218 cats (92%) categorised as indoor only, 13 cats (5%) indoor/outdoor and seven cats (3%) unspecified. No cats were fed raw diets.

3.2. Oclacitinib Treatment

Commercially available oclacitinib tablets were prescribed in 217 cats (91%). Most owners crushed the prescribed dose and mixed it with canned food. A compounded oral suspension made with an anhydrous base (SuspendRx Anhydrous Oral Suspension Vehicle, unsweetened; SpecializedRx) and optional flavouring (SpecializedRx) was dispensed for 17 cats (7%). Four cats (2%) tried both formulations.

The average initial oclacitinib dosage prescribed was 1.89 mg/kg/day (range 0.69–3.9 mg/kg/day). Most cats (162 of 238, 68%) received ≤ 2 mg/kg/day, while 72 of 238 (30%) were treated between 2 and 3 mg/kg/day and four of 238 (2%) received dosages exceeding 3 mg/kg/day.

Twice‐daily administration was initially prescribed in 222 of 238 cats (93%) (range 0.84–3.9, x̄ = 1.94 mg/kg/day) and once daily in 16 of 238 cats (7%) (range 0.69–1.86, x̄ = 1.31 mg/kg/day) owing to documented challenges with the administration of medication or concerns with owner compliance.

Fourteen cats (6%) had reported difficulty with administration resulting in a dose reduction (n = 3), reduced dose frequency (n = 4) or treatment discontinuation (n = 7).

3.3. Duration of Therapy

The median treatment duration was 271.5 days (range 1 day–7.5 years). Duration of use could be divided into the following: 41 of 238 cats (17%) ≤ 30 days; 59 of 238 cats (25%) between 30 days and 6 months; 34 of 238 cats (14%) between 6 months and 1 year; and 104 of 238 cats (44%) > 1 year.

3.4. Adverse Events

A total of 96 AEs were documented in 82 of 238 cats (34%) and categorised as follows: definite (n = 6), probable (n = 27), and possible (n = 63). Restricting the analysis to definite or probable events reduced the frequency of AEs to 33 in 32 of 238 cats (13%) (Table 3).

TABLE 3.

Likelihood of adverse events associated with oclacitinib use in 238 cats.

Category	Definite	Probable	Possible	Doubtful	Total events
Gastrointestinal (vomiting, diarrhoea, anorexia, constipation)	6	3	4	9	22
Lethargy (decline in play behaviour, increased sleeping habits, increased reclusive behaviours)	0	4	1	2	7
Respiratory (transient congestion or sneezing)	0	0	3	1	4
Behavioural (aggression, restlessness)	0	1	0	1	2
Dermatological (increased pruritus, parasitism)	0	0	1	1	2
Urinary (transient inappropriate urination)	0	0	2	0	2
Neurological (ataxia)	0	0	0	2	2
Neutropaenia	0	15	14	18	47
Elevated liver enzymes (ALP, ALT, GGT)	0	1	10	16	27
Elevated renal enzymes (creatinine, BUN, SDMA)	0	1	21	33	55
Thrombocytopaenia	0	0	1	0	1
Neoplasia	0	0	6	0	6
Infection—phaeohyphomycosis	0	1	0	0	1
Infection—FIP	0	1	0	0	1
Acute death—hypertrophic cardiomyopathy	0	0	0	1	1
Aortic thromboembolism	0	0	0	1	1
Total	6	27	63	85	181

Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; BUN, blood urea nitrogen; FIP, feline infectious peritonitis; GGT, gamma‐glutamyl transferase; SDMA, symmetrical dimethylarginine.

The most common probable AE was neutropaenia (range 1353–2470 × 10³/μL) documented in 15 cats (6.3%) including one that was FIV‐positive. All cats remained asymptomatic. Baseline complete blood counts (CBC) were available in nine of 15 cats (x̄ = 3684 × 10³/μL, range 2390–5133 × 10³/μL). Neutropaenias were classified as mild (1500–2500 × 10³/μL) in 14 of 15 cats (93%) and moderate (1000–1499 × 10³/μL) in one cat. The median time to development was 70 days (interquartile range 63–97.5 days), with 11 of 15 cats (73%) captured between 56 and 80 days. The average prescribed dosage was 1.8 mg/kg/day (median 1.95 mg/kg/day, range 0.9–2.42 mg/kg/day) which is similar to the overall study average, 1.89 mg/kg/day.

Outcomes for cats with neutropaenia were generally favourable and 13 of 15 cats continued oclacitinib long‐term. Eleven improved after a dosage reduction while two remained stable without adjustment. At the time of study conclusion, neutropaenias resolved in eight of 11 cats that underwent a dose reduction and trended towards normal in the remaining three of 11 cats. Multiple dose reductions were required in the FIV‐positive cat until the neutropaenia stabilised on 0.89 mg/kg every other day. Of the eight cats whose neutropaenias completely resolved, time to normalisation ranged from 28 to 371 days. Discontinuation was required in two of 15 cats as a result of a minimally responsive neutropaenia following one or multiple dose reductions.

Nine GI AEs were observed in nine of 238 cats (4%) including six definite and three probable cases. Time to onset ranged from 1–30 days (median 7 days) and included observation of: vomiting (n = 5), diarrhoea (n = 2) or vomiting and diarrhoea (n = 2). All cases were self‐limiting and resolved within 3 days of temporary discontinuation. Six cats required permanent discontinuation, including: vomiting (n = 4), diarrhoea (n = 1) and vomiting and diarrhoea (n = 1). All others tolerated a dose reduction.

Lethargy was documented as a probable AE in four cats (1.7%). This included and was not limited to: a decline in normal play behaviour, disinterest in their surroundings, increased reclusive behaviours and sleeping more. One cat temporarily stopped oclacitinib for 24 h and resumed use at a 50% lower dose, while the remaining three cats improved immediately after moving to once‐daily dosing.

Two cats (0.8%) developed infections; this included one case of phaeohyphomycosis confirmed via biopsy sample from the nasal planum (x̄ = 1.46 mg/kg/day, 11 months duration) and one case of feline infectious peritonitis (FIP) (x̄ = 1.64 mg/kg/day, 15 months duration). Both of these events were rated as probable. Each of these cats was indoor‐only, previously diagnosed with PF and receiving a combination of high dose corticosteroids with oclacitinib. The phaeohyphomycosis infection resolved after a 50% oclacitinib dose reduction, discontinuation of dexamethasone and itraconazole therapy. The cat with FIP underwent a brief steroid taper after diagnosis and antiviral therapy, yet the oclacitinib dosage was unchanged. Both cats remained in PF remission on oclacitinib monotherapy.

Other probable AEs attributed to oclacitinib included: hyperactivity (n = 1, 0.4%) as well as one cat with both elevated creatinine levels (n = 1, 0.4%) and elevated ALT enzymes (n = 1, 0.4%) that remained asymptomatic.

The next group of events were categorised as either doubtful or possible AEs. This included: GI signs (n = 12), respiratory signs (n = 4), increased or inappropriate urination (n = 2), lethargy (n = 3) and ataxia (n = 2). Haematological AEs included azotemia (n = 54; 33 doubtful, 21 possible), elevated liver enzymes (n = 26; 16 doubtful, 10 possible), neutropaenia (n = 32; 14 possible, 18 doubtful), and thrombocytopaenia (n = 1; possible).

Additional events each reported only once and rated as doubtful included: acute death attributed to chronic heart changes on necropsy, suspected feline aortic thromboembolism, increased pruritus that persisted following oclacitinib discontinuation, diagnosis of Demodex gatoi after oclacitinib discontinuation, aggression towards another cat despite oclacitinib cessation and episodic constipation in a cat with a history of inflammatory bowel disease later diagnosed with a colonic mass.

Six counts of neoplasia were reported in five cats receiving oclacitinib and were considered possible AEs (Table 4). Diagnoses, age at time of diagnosis, dosage and duration of oclacitinib use included: cutaneous hemangiosarcoma (9.8 years old; x̄ = 1.68 mg/kg/day; 4 years), Bowenoid in situ carcinoma (12.75 years old; x̄ = 1.55 mg/kg/day; 3 years), cutaneous lymphoma (11.4 years old; x̄ = 2.24 mg/kg/day; 5 years) and a suspected abdominal mass (14.9 years old; x̄ = 1.16 mg/kg/day; 4 years). One cat developed both a mast cell tumour after 1 year of use (3.1 years old; x̄ = 1.52 mg/kg/day) and cutaneous hemangiosarcoma after 6 years of use (8.2 years old; x̄ = 2.07 mg/day/day).

TABLE 4.

Diagnosis, workup, oclacitinib dosage and duration of use for each cat that developed neoplasia.

Cat	Age at diagnosis (years)	Sex, breed	Tumour	Confirmed? (yes/no)	Diagnostic workup	Oclacitinib dosage (mg/kg/day) at time of diagnosis	Oclacitinib duration (years) at time of diagnosis
1	12.75	MN, DSH	Bowenoid in situ carcinoma	Yes	Histopathological evaluation	1.55	3
2	11.4	MN, DSH	Gastrointestinal lymphoma	No	Unconfirmed; owner reported diagnosed by emergency veterinary surgeon	2.24	5
3	9.8	MN, Ragdoll	Cutaneous hemangiosarcoma	Yes	Confirmed via histopathological evaluation	1.68	4
4	(a) 3.1 (b) 8.2	MN, DSH	(a) Mast cell tumour (b) Cutaneous hemangiosarcoma	(a) Yes (b) Yes	(a) Histopathological evaluation (b) Histopathological evaluation	(a) 1.52 (b) 2.07	(a) 1 (b) 6
5	14.9	MN, DSH	Abdominal mass	No	Unconfirmed; owner reported found by primary veterinary surgeon	1.16	4

Abbreviations: DSH, domestic short hair; MN, male neutered.

3.5. Response to Therapy

A positive therapeutic response was documented in 160 of 238 cats (67%), including 140 CR (59%, x̄ = 1.56 mg/kg/day) and 20 PR (8%, x̄ = 1.44 mg/kg/day). Cats classified as having a CR were on oclacitinib monotherapy for their dermatosis, though several were on concurrent medications for comorbidities. Cats categorised as PR had suboptimal control of their dermatosis on oclacitinib alone and often required concomitant anti‐inflammatory and antipruritic medications to achieve control (Table 5). Most cats started showing noticeable improvements after 2–4 weeks. The most common secondary agents utilised in PR cats were glucocorticoids (15 of 20) and ciclosporin (five of 20). The remaining 78 of 238 cats (33%) lacked improvement and were categorised as NR.

TABLE 5.

List of partial response (PR) cats treated with oclacitinib and concomitant systemic anti‐inflammatory or antipruritic medications, age at oclacitinib initiation, signalment, dermatological diagnosis, final dosage of oclacitinib and concomitant medications and remission outcome.

Cat	Age (years)	Breed	Sex	Dermatological diagnosis	Final oclacitinib dosage (mg/kg/day)	Concomitant maintenance systemic medications
1	10.17	DSH	FS	FASS	0.75	Prednisolone 0.47 mg/kg daily
2	2.75	DSH	FS	FASS sensu stricto	1	Ciclosporin 6.5 mg/kg daily
3	8.41	DSH	MN	FASS sensu stricto	1.82	Prednisolone 0.5–1 mg/kg daily
4	8	DMH	FS	FASS sensu lato	0.79	Ciclosporin 7.7 mg/kg daily
5	14.83	DSH	FS	PF	1.45	Dexamethasone 0.15 mg/kg daily
6	2.25	DSH	FS	FASS sensu stricto	1.99	Dexamethasone 0.06 mg/kg every 3 days
7	2.08	DSH	MN	FASS sensu lato	1	Ciclosporin 6.87 mg/kg every other day
8	15.17	DSH	MN	FASS sensu stricto	1.96	Prednisolone 0.63 mg/kg every other day
9	4.83	DSH	MN	FASS sensu stricto	1.78	Ciclosporin 6 mg/kg daily
10	4.58	DSH	MN	FASS sensu lato	1.56	Prednisolone 0.7 mg/kg every other day
11	4.5	DSH	FS	FASS sensu stricto	1.11	Ciclosporin 5.97 mg/kg daily Dexmethasone 0.42 mg/kg every 3 days
12	21.5	DLH	MN	PF	0.96	Prednisolone 0.27 mg/kg daily
13	16.17	DSH	FS	FASS sensu lato	1.43	Prednisolone 0.89 mg/kg daily
14	6.83	DSH	FS	FASS sensu stricto	1.92	Dexamethasone 0.18 mg/kg every 3 days
15	11.33	DSH	MN	PF	1.76	Dexamethasone 0.05 mg/kg daily
16	0.41	DSH	MI	PNOE	0.53	Prednisolone 0.74 mg/kg every other day

Abbreviations: ASIT, allergen specific immunotherapy; DLH, domestic long hair; DMH, domestic medium hair; DSH, domestic short hair; FASS, feline atopic skin syndrome; FS, female spayed; MI, male intact; MN, male neutered; N/A, not applicable; PF, pemphigus foliaceus; PNOE, proliferative necrotising otitis externa; PR, partial response.

The most common primary diagnosis that achieved a CR was FASS, in 132 of 216 cats (61%, x̄ = 1.53 mg/kg/day). The second most common was PF in five of 17 cats (29%, x̄ = 1.49 mg/kg/day). Other diagnoses that successfully achieved a CR included one cat with PCP tapered from 1.90 to 0.95 mg/kg/day after 2 months and one cat with SPGS (x̄ = 1.68 mg/kg/day). A PR was noted in PNOE (x̄ = 0.53 mg/kg/day). One cat with idiopathic ulcerative dermatitis was categorised as NR (x̄ = 1.90 mg/kg/day).

Among the 140 cats with a CR, 83 (59%) were maintained on twice‐daily dosing (x̄ = 1.85 mg/kg/day) and 57 (41%) on once daily (x̄ = 1.05 mg/kg/day). Fifty‐three of 57 cats (93%) maintained on once‐daily administration initially received oclacitinib twice daily. Documented therapeutic outcomes in the 16 of 238 cats initially prescribed once‐daily administration included: four CRs, three PRs, and six NRs. Two cats did not have sufficient data to accurately assess treatment efficacy, and one additional cat achieved a CR after the dose was increased to twice daily.

3.6. Previous Immunosuppressive Treatments

Before oclacitinib administration, 177 of 238 cats (74%) trialled one or more immunosuppressive therapies. Glucocorticoids were used by 84 of 238 cats (35%), and while generally effective at the initial prescribed dose, treatment response was not recorded because it varied widely as the dose was tapered. Ciclosporin monotherapy or multimodal therapy was trialled and discontinued in 136 of 238 cats (57%). Reasons for discontinuation included: lack of disease control (41%), GI signs (24%), difficulty with administration (20.5%), lethargy (5%), ptyalism (3%), gingival hyperplasia (2%), tremors (1%), and increased sneezing (1%).

3.7. Laboratory Parameters

Haematological data were available for 178 cats (75%). Baseline CBC and chemistry values were available within 1 year of oclacitinib start date in 89 of 238 cats (37%; x̄ = 73.4 days; median 34 days; range 0–364 days). Twenty‐five urinalyses (UAs) were performed in 19 cats (8%), with eight obtained as baseline values and 17 during oclacitinib use. These additional UAs were prompted by other clinical concerns and were not part of routine oclacitinib monitoring. A follow‐up appointment with bloodwork was required within 2 months of starting oclacitinib. Additional bloodwork testing was recommended after 3 months and then every 6 months, although compliance varied.

3.8. Additional Bloodwork Findings

The most common additional finding was hypercholesterolaemia, documented in 68 of 238 cats (29%). Other mild and often transient alterations documented in individual cats included: elevations in eosinophils, monocytes, lymphocytes, and red blood cells, as well as glucose, total protein, albumin, globulin, and total calcium. Mild decreases were documented in total protein, globulin, lymphocytes, and red blood cells. None of these abnormalities resulted in known health concerns, and they were not graded as AEs.

4. Discussion

This case series investigated both the safety and efficacy of off‐label oclacitinib therapy in cats and found it to be well‐tolerated and effective in managing FASS and other immune‐mediated dermatoses. This also is the largest and longest evaluation of oclacitinib use in cats to date.

The most common AE recognised in cats receiving oclacitinib was a mild neutropaenia. In dogs, the frequency, individual dose and total daily dose of oclacitinib influence its plasma concentration [42]. Prolonged elevations increase the likelihood of JAK2‐dependent cytokine inhibition, increasing the risk of haematopoietic adverse effects [43]. Until similar safety studies are performed in cats, conclusions regarding the influence of dose, dosage and frequency cannot be made.

Neutropaenia in dogs typically develops between 1 and 3 months [23]; however, feline studies have been too limited in size and duration to establish similar parameters. To the best of the authors' knowledge, only two cases of neutropaenia have been reported in cats following 28 days of use at 1.8 mg/kg/day [27]. The limited reporting may be a consequence of the lack of long‐term follow‐up, as 11 of 15 cats with neutropaenia in this study were first identified between 56 and 80 days after treatment initiation. Despite the absence of clinical signs in the neutropenic cats from this study, continuous clinical monitoring is recommended to avoid development of a progressive neutropaenia. Baseline CBC with follow‐up monitoring at 2 and 5 months, then annually, along with clinical monitoring, was adequate in most cases.

In agreement with the literature, GI AEs were sporadically reported [29]. Although the mechanism remains unclear, seven of nine cats with GI AEs had a history of episodic vomiting or diarrhoea, and developed similar clinical signs while trialling other immunosuppressive therapies, suggesting that cats with a history of GI signs may be more likely to develop GI signs with oclacitinib.

Although not considered an AE, seven of 238 cat owners discontinued oclacitinib because administration was too difficult. This is much lower than ciclosporin discontinuation rates, which are as high as 21% [7]. In our study, prior refusal of ciclosporin was not a predictive factor for difficulties with oclacitinib.

Elevations of ALT have been infrequently reported in cats related to oclacitinib [25, 31]. In this study, one cat with a probable AE developed both a transient, mild ALT and creatinine elevation after 2 months of therapy and resolved following a dose reduction. Another cat receiving 2.44 mg/kg/day had a possible ALT AE, with ALT nearly seven‐fold greater than the reference range and concurrent hyperbilirubinaemia. Baseline bloodwork had been normal, however this cat was 18 years old, had a 1 week history of anorexia and had been off oclacitinib for nearly 2 weeks when bloodwork was checked. While oclacitinib may have prompted these abnormalities, the age of the cat and potential for internal disease and concurrent hepatic lipidosis should not be overlooked.

Mild creatinine elevations were sporadically observed which may be attributed to oclacitinib use; however, the average age of the impacted cats aligned with the average age of chronic kidney disease onset [44]. Conclusions about renal status cannot be made without a concurrent urinalysis and symmetric dimethylarginine (SDMA) and BUN values. Furthermore, previous ingestions causing acute kidney injury were nearly four‐fold higher than the dosages observed in this study [37].

Hypercholestolaemia was documented in 68 of 238 cats. Elevations in cholesterol have been reported with JAK inhibitor administration in dog [13, 22], human [45] and feline studies [31]. Human studies indicate that hypercholesterolaemia is a result of interleukin (IL)‐6 inhibition which is a cytokine also downregulated by oclacitinib [46, 47]. No clinical significance is reported in any species.

Three cats experienced increased upper respiratory signs. These AEs were categorised as possible and occurred between 2 months and > 1 year after starting oclacitinib. This may be due to the result of reactivation of viral disease such as Feline Herpesvirus‐1 (FHV‐1) and the frequency matched other immunosuppressants [48].

Limited information is available regarding the risk of oclacitinib therapy in FIV‐ or FeLV‐positive cats. One FIV‐positive cat in our study experienced a progressive neutropaenia until the dose was dramatically reduced. These cats may require closer monitoring or avoidance of oclacitinib therapy.

Two indoor‐only cats with PF receiving a combination of glucocorticoids and oclacitinib developed infections, including FIP and phaeohyphomycosis. Both cats demonstrated rapid clinical improvement following discontinuation of glucocorticoids and stayed on oclacitinib therapy to manage their PF. These cases suggest that oclacitinib may increase the risk of developing infectious diseases, especially when used in combination with other immunosuppressants.

Six types of neoplasia were reported in five cats. While the role of oclacitinib in the development of neoplasia in cats is not fully known, an age‐ and breed‐matched canine retrospective study found no association between long‐term oclacitinib and a higher neoplasia incidence [49].

The average initial oclacitinib dosage prescribed in this case series was comparable with the majority of other studies. Previously, dosages of ≤ 4 mg/kg/day have appeared to be well‐tolerated for ≤ 28 days [29] and all four cats in this case series who received dosages > 3 mg/kg/day for refractory FASS or PF had no AEs noted.

In alignment with previous reports [25, 26, 31], some cats (41%) maintained control of their primary dermatosis with once‐daily administration; however, it was not standard protocol to reduce the dose unless there were concerns and CR was documented.

The retrospective design of this study limits the ability to establish causal relationships. As a result, an overestimation of AEs may have occurred, particularly within the possible category which accounted for nearly two‐thirds of rated AEs. This category represents a lower level of confidence in causality because alternative explanations were often equally plausible or lacked follow‐up. Conversely, some AEs may have been missed owing to inconsistencies in record‐keeping and monitoring.

One additional important limitation was that baseline diagnostics (CBC, chemistry, UA) were not available for most cases, and the frequency at which they were conducted varied depending on the clinician's preference and owner compliance. Finally, there is a lack of standardised assessment scales for evaluating drug‐induced AEs and treatment efficacy in cats. The retrospective design made it difficult to establish clear efficacy end‐points, which made the interpretation fairly subjective and prone to bias. Prospective, controlled studies using validated scoring systems are needed to build on the findings from this study and investigate the potential causal relationships between oclacitinib, AEs and treatment efficacy.

5. Conclusion

This study found that oclacitinib appears to be a safe and effective off‐label therapeutic option in cats, particularly for FASS and PF, when classical therapies fail or are contraindicated. Housing and environmental safety measures, similar to those outlined for ciclosporin, should be followed, and clinicians prescribing oclacitinib should anticipate a similar profile of mild, typically manageable AEs to that in dogs, often responsive to temporary discontinuation or a dose reduction.

Author Contributions

Marlyse R. Wehber: conceptualization, investigation, writing – original draft, methodology, visualization, writing – review and editing, formal analysis, data curation, resources. Melissa C. Eisenschenk: supervision, project administration, methodology, writing – review and editing. Amanda J. Young: conceptualization, methodology, writing – review and editing. Sandra N. Koch: conceptualization, writing – review and editing.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Wehber M. R., Eisenschenk M. C., Young A. J., and Koch S. N., “A Retrospective Case Series Reporting the Clinical Efficacy and Adverse Events of Oclacitinib Administration for Skin Disease in 238 Cats,” Veterinary Dermatology 37, no. 4 (2026): 557–566, 10.1111/vde.70077.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.