Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies

Abstract

Objective: Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib.

Methods: Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic disease-modifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Δ) in C-reactive protein, HAQ-DI, Patient's/Physician's Global Assessment of Arthritis, and patient-reported outcomes. Safety outcomes included treatment-emergent all-causality adverse events (AEs), Δ in lipid/hepatic values, and liver parameter increases.

Results: Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Δ in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinib-treated patients with MetS.

Conclusion: Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS.

Figure 1

Response rate (SE) for ACR20 (A), ACR50 (B), ACR70 (C), PASI75^a (D), and HAQ‐DI response^b (E), enthesitis resolution^c (F) and dactylitis resolution^d (G) rates at months 3 and 6, by treatment group and baseline MetS status; pooled data from OPAL Broaden and OPAL Beyond. ^aPASI was assessed only in patients with baseline BSA ≥ 3% and PASI > 0. ^bHAQ‐DI response is defined as a decrease ≥ 0.35 among patients with baseline HAQ‐DI score ≥ 0.35. ^cEnthesitis resolution was assessed only in patients with baseline LEI > 0. ^dDactylitis resolution was assessed only in patients with baseline DSS > 0. A patient with a missing value was considered a nonresponder. Abbreviations: ACR, American College of Rheumatology; BID, twice daily; BSA, body surface area; DSS, Dactylitis Severity Score; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; LEI, Leeds Enthesitis Index; MetS, metabolic syndrome; N, number of patients with nonmissing baseline MetS; PASI, Psoriasis Area and Severity Index; SE, standard error.

Figure 2

LS mean (SE) change from baseline in HAQ‐DI (A), PGA (VAS, mm) (B), PtGA (VAS, mm) (C), Pain (VAS, mm) (D), and FACIT‐F total score (E) at months 3 and 6 by treatment group and baseline MetS status, and mean (SE) change from baseline in CRP (F), at months 3 and 6, by treatment group, baseline MetS status, and baseline CRP ≤ 2.87 mg/L and > 2.87 mg/L; pooled data from OPAL Broaden and OPAL Beyond. Each of the endpoints (except CRP) were analyzed using a mixed model for repeated measures, with fixed effects of treatment, visit, study, treatment‐by‐visit, baseline MetS, treatment‐by‐baseline MetS, visit‐by‐baseline MetS, treatment‐by‐visit‐by‐baseline MetS interactions, geographical region, and baseline value. Missing values were not imputed. A common unstructured covariance matrix was used. LS mean (SE) changes from baseline were calculated at months 3 and 6 using two separate models. Results at month 3 were based on a model that included tofacitinib 5 mg BID, tofacitinib 10 mg BID, and placebo treatment groups; as the placebo treatment group was only included up to month 3 (end of placebo‐controlled period), the results at month 6 were based on a separate model that included only tofacitinib 5 mg BID and tofacitinib 10 mg BID treatment groups. Arithmetic mean (SE) was calculated for change from baseline in CRP by treatment group, baseline MetS status, and CRP cutoff. Abbreviations: Δ, change from baseline; BID, twice daily; CRP, C‐reactive protein; FACIT‐F, Functional Assessment of Chronic Illness Therapy‐Fatigue; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; LS mean, least squares mean; MetS, metabolic syndrome; N, number of patients evaluable at months 3 and 6; PtGA, Patient’s Global Assessment of Arthritis; PGA, Physician’s Global Assessment of Arthritis; SE, standard error; VAS, Visual Analog Scale.