Efficacy of Tofacitinib for the Treatment of Psoriatic Arthritis: Pooled Analysis of Two Phase 3 Studies

Abstract

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed the efficacy of tofacitinib using pooled data from two phase 3 studies of patients with active PsA.

Methods: Data were pooled from OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439). Patients had active PsA and either an inadequate response (IR) to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and were tumor necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden), or had IR to ≥ 1 TNFi (OPAL Beyond). Pooled data included tofacitinib 5 or 10 mg twice daily (BID; to month 6) and placebo (to month 3; patients then switched to tofacitinib 5 or 10 mg BID). Patients also received one background csDMARD. Endpoints included American College of Rheumatology (ACR)20 response and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at month 3 (primary endpoints), ACR50/70 response, HAQ-DI response (decrease from baseline ≥ 0.35) and improvements in painful and swollen joint counts, psoriasis, enthesitis and dactylitis to month 6.

Results: A total of 710 patients were included (tofacitinib 5 mg BID: 238; tofacitinib 10 mg BID: 236; placebo: 236). Primary endpoints showed significant improvements at month 3 in patients receiving tofacitinib 5 or 10 mg BID vs. placebo. Significant improvements in HAQ-DI response, painful and swollen joints, psoriasis, enthesitis and dactylitis vs. placebo were observed for both tofacitinib doses at month 3. Efficacy was maintained to month 6 (final pooled time point).

Conclusions: In a pooled analysis of csDMARD-IR/TNFi-naïve and TNFi-IR patients, tofacitinib was superior to placebo at month 3 across four PsA domains: peripheral arthritis, psoriasis, enthesitis and dactylitis.

Trial registration: OPAL Broaden (NCT01877668); OPAL Beyond (NCT01882439).

Funding: Pfizer Inc.

Keywords: Janus kinase inhibitor; Psoriatic arthritis; Spondyloarthritis; Tofacitinib; Treatment.

Figures

Fig. 1

ACR20, ACR50, and ACR70 response rates at month 3; pooled data from OPAL Broaden and OPAL Beyond (FAS, NRI). ACR American College of Rheumatology, BID twice daily, FAS Full Analysis Set, NRI non-response imputation, SE standard error. *p ≤ 0.05; **p < 0.01; ***p < 0.001 vs. placebo; p values are based on large sample approximation to difference in binomial proportions adjusting for study by Cochran–Mantel–Haenszel approach; missing response was imputed as non-response

Fig. 2

ACR20, ACR50, and ACR70 response rates to month 6; pooled data from OPAL Broaden and OPAL Beyond (FAS, NRI). ACR American College of Rheumatology, BID twice daily, FAS Full Analysis Set, NRI non-response imputation, RR response rate in terms of ACR response, SE standard error. *p ≤ 0.05; **p < 0.01; ***p < 0.001 vs. placebo; p values are based on large sample approximation to difference in binomial proportions adjusting for study by Cochran–Mantel–Haenszel approach; p values not calculated beyond month 3 as the placebo-controlled period ended at month 3; missing response was imputed as non-response

Fig. 3

LSM change from baseline in HAQ-DI, painful/tender JC and swollen JC, PASI75 response rate and LSM change from baseline in DLQI to month 6; pooled data from OPAL Broaden and OPAL Beyond. BID twice daily, BSA body surface area, CFB change from baseline, DLQI Dermatology Life Quality Index, HAQ-DI Health Assessment Questionnaire-Disability Index, JC joint count, LSM least squares mean, PASI Psoriasis Area and Severity Index, RR response rate in terms of PASI75, SE standard error. *p ≤ 0.05; **p < 0.01; ***p < 0.001 vs. placebo; p values for HAQ-DI, painful/tender JC, swollen JC and DLQI are based on mixed model for repeated measures without imputation for missing values; p values for PASI75 are based on large sample approximation to difference in binomial proportions adjusting for study by Cochran–Mantel–Haenszel approach; missing response was imputed as non-response; p values not calculated beyond month 3 as the placebo-controlled period ended at month 3. aOut of 68 joints; bOut of 66 joints. N for HAQ-DI, painful/tender JC, swollen JC and DLQI is the number of patients evaluable at each visit; N for PASI75 is the number of patients with baseline BSA ≥ 3% and PASI > 0

Fig. 4

LSM change from baseline in LEI, SPARCC Enthesitis Index, DSS and BASDAI to month 6; pooled data from OPAL Broaden and OPAL Beyond. BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BID twice daily, CFB change from baseline, DSS Dactylitis Severity Score, LEI Leeds Enthesitis Index, LSM least squares mean, N number of patients evaluable at each visit, SE standard error, SPARCC Spondyloarthritis Research Consortium of Canada. *p ≤ 0.05; **p < 0.01; ***p < 0.001 vs. placebo; p values are based on mixed model for repeated measures without imputation for missing values; p values not calculated beyond month 3 as the placebo-controlled period ended at month 3. aPatients with baseline score > 0; bPatients with spondylitis (as determined by the investigator site’s qualified assessor) at screening and baseline BASDAI > 0 cm; cPatients with spondylitis (as determined by the investigator site’s qualified assessor) at screening and baseline BASDAI ≥ 4 cm