Long-Term Efficacy and Safety of Tofacitinib in Patients With Psoriatic Arthritis Analyzed

senior woman with arthritis holding prescription medicine pill bottle
In the final analysis of the OPAL Balance study, researchers assessed the safety, tolerability, and efficacy of tofacitinib in patients with active psoriatic arthritis.

In patients with active psoriatic arthritis (PsA), treatment with tofacitinib is associated with long-term efficacy (up to 36 months) and safety (up to 48 months), according to results of an analysis published in Lancet Rheumatology.

Researchers sought to evaluate the long-term safety and efficacy of tofacitinib in adult patients with active PsA.

The open-label, long-term extension study — the final analysis of the Oral Psoriatic Arthritis Trial (OPAL) Balance study (ClinicalTrials.gov Identifier: NCT01976364) — was conducted at 124 centers in 16 countries.

Primary study endpoints included incidence of clinical laboratory abnormalities, changes from baseline in laboratory parameters up to 48 months in patients from the long-term extension study and substudy, and incidence and severity of adverse events (AEs). Eligible patients in OPAL Balance study had also participated in the OPAL Broaden or the OPAL Beyond phase 3 trials.

In the OPAL Balance study, all participants received open-label tofacitinib 5 mg twice daily, with dose escalations to 10 mg twice daily at month 1 for inadequate symptom control, as well as reductions to 5 mg twice daily thereafter for safety. All participants could continue to receive concomitant treatment with specific conventional synthetic disease-modifying antirheumatic drugs. Eligible patients could also enter the randomized, double-blind methotrexate withdrawal substudy, in which participants received open-label tofacitinib 5 mg twice daily plus either masked methotrexate or masked placebo.

A total of 686 participants were enrolled in OPAL Balance study, between February 17, 2014, and March 28, 2016, who received treatment with tofacitinib and were enrolled in the all-tofacitinib group for the safety and efficacy analyses. Ultimately, 66% (n=453) of participants completed this study and 34% (n=233) discontinued their participation in either the long-term extension study or the methotrexate withdrawal substudy. In the all-tofacitinib group, the mean duration of tofacitinib treatment was 794.6 days and the total duration of treatment was 1492.4 person-years in the long-term extension study. Mean age of the participants in the all-tofacitinib group was 48.8 years; 54% of the participants were women; mean duration of PsA was 7.6 years.

Up to month 48, 84% (n=574) of participants reported the occurrence of all-cause AEs, with 17% experiencing serious AEs and 11% discontinuing treatment because of an AE. Overall, 6 patients died, among whom 1 was within the risk period (incidence of death was 0.1 patients with events [95% CI, 0.0-0.3] per 100 person-years). Incidences of AEs of special interest, which was defined as the number of patients with events per 100 person-years, included the following: 1.7 (95% CI, 1.2-2.5) for herpes zoster; 1.0 (95% CI, 0.6-1.6) for serious infections; 0.4 (95% CI, 0.1-0.8) for opportunistic infections; 0.7 (95% CI, 0.4-1.2) for malignancies other than nonmelanoma skin cancer (NMSC); 0.9 (95% CI, 0.5-1.5) for NMSC; 0.2 (95% CI, 0.1-0.6) for major adverse cardiovascular events; 0.4 (95% CI, 0.1-0.8) for arterial thromboembolism; and 0.1 (95% CI, 0.0-0.3) for pulmonary embolism. Efficacy was sustained for up to 36 months.

A major limitation of the current study included the lack of generalizability to patients who are new to tofacitinib treatment. Further, the long-term extension study was open-label and had no placebo group; the analyses used observed values; and evaluations of dose-related effects were conducted post hoc.

Researchers concluded that the data reported in this trial “support the use of tofacitinib in the long-term treatment of active [PsA].”

Disclosure: This analysis was supported by Pfizer. Please see the original reference for a full list of authors’ disclosure.


Nash P, Coates LC, Fleishaker D, et al. Safety and efficacy of tofacitinib up to 48 months in patients with active psoriatic arthritis: final analysis of the OPAL Balance long-term extension study. Lancet Rheumatol. 2021;3:270-283. doi:10.1016/S2665-9913(21)00010-2