Pfizer presented positive results from its Phase 3 OPAL clinical program evaluating the effectiveness and safety of Xeljanz (tofacitinib citrate) in adult patients with active psoriatic arthritis (PsA), who had an inadequate response to conventional treatments.
The results were presented at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting (2016 ACR/ARHP), which took place in Washington, D.C.
Xeljanz, a Janus kinase (JAK) inhibitor, is an FDA-approved oral treatment for moderate to severe rheumatoid arthritis (RA) in people who fail to respond to, or unable to use, methotrexate.
The Phase 3 studies — called OPAL BROADEN (NCT01877668), and OPAL BEYOND (NCT01882439) — evaluated Xeljanz in adult PsA patients with poor response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to tumor necrosis factor inhibitors (TNFis).
“As the only JAK inhibitor being investigated in psoriatic arthritis, tofacitinib, if approved, would provide patients and healthcare professionals the first medicine in a new class to treat this disease. We continue to progress the OPAL clinical development program globally and look forward to possible future regulatory filings,” Michael Corbo, Pfizer’s chief development officer of inflammation & immunology, said in a press release.
Both studies met their primary efficacy endpoints of significant improvement compared to placebo as measured by the American College of Rheumatology 20 (ACR20) response at three months, and by the change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) score.
OPAL BROADEN was a 12-month trial, with a three-month placebo period, evaluating the effectiveness and safety of Xeljanz 5 mg in 107 people and 10 mg in 104 people, against adalimumab 40 mg (106 patients) or placebo (105 patients). The study was not designed to judge the two treatments, Xeljanz and adalimumab, for superiority.
ACR20 response — used to assess 20% improvement in tender or swollen joints in certain parameters — was achieved in 50.5% and 60.6% of patients in 5 mg and 10 mg Xeljanz groups, respectively, at three months. A similar response, 51.9% of patients, was seen in the adalimumab group, while ACR20 response was recorded in 33.3% of people taking placebo.
OPAL BEYOND was a six-month trial, also with a three-month placebo period, and focused particularly on PsA patients who had poor response to at least one TNFi. The trial assessed the effectiveness and safety of Xeljanz 5 mg (131 patients) and 10 mg (132 patients), comparing the results with 131 patients taking placebo.
Here, ACR20 response with Xeljanz 5 mg and 10 mg was achieved by 49.6% and 47.0% of patients, respectively, while response was seen in 23.7% of those given placebo at three months.
In both studies, changes from baseline in HAQ-DI scores — a self-assessment of disability levels —showed statistically significant improvement with Xeljanz against placebo.
Most common adverse reactions in both trials were upper respiratory tract infection, nasopharyngitis and headache, and were consistent with those in previous clinical trials of this treatment.
“The findings from OPAL Broaden and OPAL Beyond showed that treatment with tofacitinib improved symptoms and decreased disease activity in patients with active psoriatic arthritis who do not respond well to currently available therapies, including DMARDs and TNFis,” said Philip Mease, MD, from the Swedish Medical Center and University of Washington. “Tofacitinib, if approved, may be an important treatment option for people with active psoriatic arthritis.”
PsA, a chronic inflammatory disease, causes joint pain and stiffness, skin and nail psoriasis, swollen toes and fingers, persistent painful tendonitis, and can result in irreversible joint damage.
