Efficacy and safety of tofacitinib in an open-label, long-term extension study in patients with psoriatic arthritis who received adalimumab or tofacitinib in a Phase 3 randomized controlled study: a post hoc analysis

Abstract

Background: Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib.

Methods: Patients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years).

Results: Overall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study.

Conclusion: Tofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period.

Trial registration: NCT01877668; NCT01976364.

Keywords: Adalimumab; Psoriatic arthritis; Tofacitinib; Treatment switching.

Fig. 1

Efficacy outcomes in the Phase 3 and LTE studies. *p < 0.05 for comparison between treatment groups. -3 months: 3 months prior to the last visit in the Phase 3 study. Last visit: the last visit in the Phase 3 study. Month 3: month 3 in the LTE study. Month 6: month 6 in the LTE study. Baseline refers to the baseline visit of the Phase 3 study. ^aIn patients with baseline HAQ-DI ≥ 0.35 (N = 77). ^bResults are based on a repeated measures model with the fixed effects of treatment, visit, treatment by visit interaction, geographic location, and baseline value – an unstructured covariance matrix was used. ACR20: ≥ 20% improvement in American College of Rheumatology response criteria, ADA: adalimumab, BID: twice daily, FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI: Health Assessment Questionnaire-Disability Index, LS: least squares, LTE: long-term extension, MDA: minimal disease activity, N: number of patients in the LTE safety analysis set, n: number of patients with response, N1: number of patients with non-missing response at visit, N2: number of patients with observations at visit, N3: number of patients included in the mixed model for repeated measures, PASDAS: Psoriatic Arthritis Disease Activity Score, PASI75: ≥ 75% Psoriasis Area and Severity Index improvement from baseline, SE: standard error

Fig. 2

Efficacy outcomes after switching from ADA→tofacitinib 5 mg BID according to Phase 3 ADA response. Efficacy outcomes for patients in the ADA→tofacitinib 5 mg BID group are shown following switch to tofacitinib in the LTE study according to ADA response in the Phase 3 study. ^aFigure excludes one patient in the ADA→tofacitinib 5 mg BID group who had a missing response to ADA at the Phase 3 last visit and no response to tofacitinib at the month 3 LTE. ^bIn patients with baseline HAQ-DI ≥ 0.35. ^cFigure excludes one patient in the ADA→tofacitinib 5 mg BID group who had a missing response to ADA at the Phase 3 last visit and a response to tofacitinib at the month 3 LTE. ACR20: ≥ 20% improvement in American College of Rheumatology response criteria, ADA: adalimumab, BID: twice daily, HAQ-DI: Health Assessment Questionnaire-Disability Index, LTE: long-term extension, MDA: minimal disease activity, n: number of patients in category, P3: Phase 3, PASDAS: Psoriatic Arthritis Disease Activity Score, PASI75: ≥ 75% Psoriasis Area and Severity Index improvement from baseline

Fig. 3

Incidence of safety outcomes in the Phase 3 and LTE studies. Total follow-up time calculated up to the first day of the first event, subject to a risk period of 28 days beyond the last dose or to the data cut-off date. Gaps in dosing between treatment switches or between the Phase 3 and LTE studies are included up to 28 days or to the data cut-off date. ADA: adalimumab, BID: twice daily, CI: confidence interval, IR: incidence rate, LTE: long-term extension, N: number of evaluable patients, n: number of patients with events, SAE: serious adverse event, TEAE: treatment-emergent adverse event