Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study

Abstract

Objectives: Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.

Methods: Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded).

Primary endpoint: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.

Results: The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported.

Conclusion: In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications.

Trial registration number: NCT03486457.

Keywords: Arthritis; Arthritis, Psoriatic; Inflammation.

Figure 1

Patient disposition. AE, adverse event; BID, twice daily; FAS, full analysis set; n, number of patients; SAS, safety analysis set.

Figure 2

(A) ACR20, (B) ACR50 and (C) ACR70 response rates to month 6 in Chinese patients with PsA.†‡ The dotted line at month 3 represents the time point at which patients in the placebo group were switched to tofacitinib 5 mg BID from month 3 for the remainder of the study. *p<0.05, **p<0.01, ***p<0.001 versus placebo (through month 3) or placebo→tofacitinib 5 mg BID (for remainder of study). †All randomised patients who received ≥1 dose of study medication. ‡Missing values were considered as non-response. ACR, American College of Rheumatology; ACR20/50/70, ≥20/50/70% improvement, respectively, in ACR response criteria; BID, twice daily; M, month; n, number of patients meeting response criteria; N, number of patients in full analysis set; PBO, placebo; PsA, psoriatic arthritis; SE, standard error; W, week.

Figure 3

(A) PASI75 response rates†, (B) resolution rates of enthesitis‡, (C) resolution rates of dactylitis§, (D) change from baseline in HAQ-DI, (E) SF-36v2 PCS and (F) SF-36v2 MCS (full analysis set).¶†† The dotted line at/after month 3 indicates that patients in the placebo group were switched to tofacitinib 5 mg BID from month 3 for the remainder of the study. *p<0.05; **p<0.01; ***p<0.001 versus placebo (through month 3) or placebo→tofacitinib 5 mg BID (for remainder of study). †Assessed in patients with baseline psoriatic BSA ≥3% and baseline PASI >0. ‡Assessed in patients with baseline LEI >0, with resolution of enthesitis defined as LEI=0. §Assessed in patients with baseline DSS >0, with resolution of dactylitis defined as DSS=0. ¶All randomised patients who received ≥1 dose of study medication. ††For response outcomes, missing values were considered as non-response. For change from baseline, missing values were not imputed. ∆, change from baseline; BID, twice daily; BSA, body surface area; CI, confidence interval; DSS, Dactylitis Severity Score; HAQ-DI, Health Assessment Questionnaire-Disability Index; LEI, Leeds Enthesitis Index; M, month; MCS, Mental Component Summary; N, number of patients in full analysis set; N1, number of patients assessed; N2, number of patients with observations at study visit; n, number of patients meeting response criteria; PASI, Psoriasis Area and Severity Index; PBO, placebo; PCS, Physical Component Summary; SE, standard error; SF-36v2, Short Form-36 Health Survey version 2 acute; W, week.