FDA Approves Tofacitinib (XELJANZ) for Active Psoriatic Arthritis

The US Food and Drug Administration (FDA) has approved 5 mg twice-daily tofacitinib (XELJANZ) and an extended release once-daily therapy (XELJANZ XR) for the treatment of adult patients with active psoriatic arthritis (PsA) who have had inadequate response or intolerance to disease-modifying antirheumatic drugs (DMARDs).

The treatment, from Pfizer, is the first Janus kinase (JAK) inhibitor approved by the FDA for moderate to severe rheumatoid arthritis (RA) and active PSA.

The approval was based on data from the phase 3 Oral Psoriatic Arthritis Trial (OPAL) program, featuring 2 pivotal studies (OPAL Broaden, OPAL Beyond) and an ongoing long-term extension trial (OPAL Balance).

In the OPAL Broaden trial, a 12-month, double-blind, active and placebo controlled study randomly assigned 422 patients with PsA who had inadequate response to DMARDs to 4 regimens. The regimens included twice-daily oral 5 mg tofacitinib (107), twice-daily oral 10 mg tofacitinib (104), 40 mg subcutaneous adalimumab once every 2 weeks (106), placebo with a blinded switch to 5 mg tofacitinib at 3 months (52), or placebo with a blinded switch to 10 mg tofacitinib at 3 months (53).

The primary endpoints were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response — as gauged by an improvement of greater than 20% from baseline in the number of tender and swollen joints — and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at month 3.

The HAQ-DI score ranges from 0 to 3, with higher numbers indicating greater disability in a patient.

At month 3, 50% of 5 mg tofacitinib patients reported an ACR20 response, and 61% of the mg tofacitinib patients did as well. In comparison, 33% of placebo patients reported an ACR20 response (p = 0.001 versus 5 mg tofacitinib, p <0.001 versus 10 mg), and 52% of adalimumab did as well.

The mean change in HAQ-DI scores for the 5 mg tofacitinib patients was -0.35, and -0.40 in the 10 mg tofacitinib patients. They were an improvement versus placebo patients’ mean -0.18 (p = 0.006 versus 5 mg; p = <0.001 verus 10 mg). The adalimumab patients again scored better than 5 mg tofacitinib patients, reporting a mean -0.38 score change.

In the OPAL Beyond trial, 395 patients with PsA wiho had previous inadequate response to TNF inhibitors were again randomized 2:2:1:1 into the 4 treatment regimens, only now studied over 6 months. Reporting safety and tolerability, researchers reported that 4% and 6% of the 5 mg and 10 mg tofacitinib patient groups reported serious adverse events, respectively.

Over 6 months, there were 4 serious infections, 3 herpes zoster infections, 1 myocardial infarction, and 1 ischemic stroke among the continuous tofacitinib patient group.

Overall, both pivotal studies met their 2 primary efficacy endpoints and demonstrated statistically significant improvement in the 2 score metrics for treatment. The observed safety profile in patients with PsA treated with tofacitinib was consistent with that observed in rheumatoid arthritis patients.

“Psoriatic arthritis is a complex and progressive disease with an unpredictable course,” Angela Hwang, Global President of Inflammation and Immunology at Pfizer, said. “The approval of XELJANZ is an important step forward for patients seeking new treatments and is a testament to Pfizer’s unwavering commitment to advancing patient care.”