Tofacitinib Shows Positive Results in Phase 3 Psoriatic Arthritis Trial

Top-line results from a phase 3 trial indicate that twice-daily tofacitinib (Xeljanz) 5 mg and 10 mg are both superior to placebo in the treatment of psoriatic arthritis.

Superiority to placebo had been the primary endpoint for OPAL (Oral Psoriatic Arthritis triaL) Broaden, which randomized 422 patients 2:2:2:1:1 among twice-daily tofacitinib 5 mg, twice-daily tofacitinib 10 mg, adalimumab 40 mg, and 2 placebo arms — the first of which transitioned to twice daily tofacitinib 5 mg after 3 months and then second of which transitioned to tofacitinib 10 mg after 3 months.

The study measured tofacitinib’s relative performance against placebo by comparing the percentage of patients who achieved ACR20 responses (ie a 20% reduction in disease symptoms as measured by the American College of Rheumatology scale) and by scores on the Health Assessment Questionnaire Disability Index (HAQ-DI).

According to Pfizer, who manufactures tofacitinib, the study was not powered to compare tofacitinib performance against adalimumab [Humira], which was only used in the trial to provide an active control arm.

At baseline, all patients were naïve to tumor necrosis factor inhibitors and had an inadequate response to conventional disease-modifying anti-rheumatic drugs. Pfizer did not provide any specifics about results for patients on either dose of tofacitinib, adalimumab or placebo.

“Despite available therapies, including biologic and oral treatments, there remains an unmet need for additional options,” said Michael Corbo in a news release.

Corbo is Category Development Lead, Inflammation & Immunology, for Pfizer Global Innovative Pharmaceuticals Business. He also noted that “the results seen in the OPAL Broaden study are encouraging as they suggest that tofacitinib may have the potential to offer an additional effective oral option for patients living with psoriatic arthritis. We look forward to sharing detailed results at a future scientific meeting.”

Tofacitinib is a Janus kinase inhibitor that the FDA approved for the treatment of rheumatoid arthritis in late 2012. European regulators are currently reviewing a submission petitioning them for a similar approval in the European Union.

OPAL Broaden, along with another trial called OPAL Beyond and a long-term extension study called OPAL Balance, is designed to provide the data needed to secure permission to market tofacitinib in the U.S. as a treatment for psoriatic arthritis. Pfizer has not indicated when it hopes to submit an application for the new indication.

If tofacitinib were to be approved for the treatment of psoriatic arthritis, it would join a growing number of medications that can attack the disease in a growing number of ways. Earlier this year, the FDA used trials against placebo to justify the approval of an interleukin-17A inhibitor called secukinumab (Cosentyx) for the treatment of psoriatic arthritis.

In 1 year-long trial on 100 patients, 54% of the patients who received the 300 mg dose (p<0.0001) and 51% who received the 150 mg dose (p<0.0001) achieved an ACR20 response after 24 weeks. By the 1-year point, 64% of the patients who received either the 300 mg dose or the 150 mg dose met ACR 20 response criteria.

Secukinumab’s approval came roughly 2 years after the FDA approved apremilast (Otezla), an inhibitor of phosphodiesterase 4 that — like tofacitinib but unlike the injectable secukinumab &mdash; is taken as a pill.