Two Investigational Drugs to Treat Psoriatic Arthritis on the Horizon
Tofacitinib and Guselkumab show promise in patients with PsA.
Data from 2 studies support the use of 2 new drug classes to treat psoriatic arthritis (PsA).
The studies examined the investigative oral Janus kinase inhibitors tofacitinib and guselkumab in patients with PsA.
The first study included 422 patients with active PsA who did not receive prior treatment with an anti-TNF agent. Participants were randomized to receive either 5 mg or 10 mg of tofacitinib twice-daily, 40-mg subcutaneous injection of adalimumab every 2 weeks, or placebo.
At 3 months, the results of the study showed that patients who received either 5 mg or 10 mg of tofacitinib experienced a statistically significant improvement compared with placebo in ACR20 response rates and change from baseline in the HAQ-DI score.
“Despite the differences emerging in the pathophysiology of PsA and the rheumatoid arthritis, tofacitinib, which works on many different cytokines, shows efficacy in the treatment of both conditions,” said lead author Philip J. Mease. “Since tofacitinib is a tablet and not an injection, once it receives regulatory approval, it is likely to be popular with both physicians and patients.”
Tofacitinib was superior to placebo for ACR20 response rates as early as week 2, with responses maintained for 12 months. Furthermore, the investigators observed greater efficacy for adalimumab compared with placebo.
There were no new safety risks identified compared with prior studies in other indications. The most common adverse events (AEs) were upper respiratory tract infection, nasopharyngitis, and headache.
The results of the phase 2a study showed that significantly more patients treated with guselkumab achieved ACR 20/50/70 response and Psoriasis Area Severity Index (PASI) 75/90/100 responses at week 24.
Nearly 40% of patients in the active group achieved PASI 100—–completely clear skin––at week 24 compared with 6.3% of patients in the placebo arm.
“Guselkumab, which targets IL-23, appears to be a promising new treatment of PsA,” said lead author Atul Deodhar. “Although anti-TNF treatments have revolutionized the management of psoriatic arthritis, new next-generation therapies are needed in the treatment of this disease.”
Twenty-one percent of patients in the guselkumab experienced significant improvement in joint symptoms, physical function, psoriasis, enthesitis, dactylitis, and quality of life, compared with 0% in the placebo arm.
The ACR-response in the active arm increased with time, with 58% of subjects achieving a 20% improvement in joint symptoms at week 24 compared with 18.4% in the placebo arm, according to the study. Fourteen percent of patients in the guselkumab arm achieved ACR70 compared with 2% in the placebo arm at week 24.
Among patients with enthesitis at baseline, 29% of patients in the placebo arm experienced resolved enthesitis at week 24 compared with 56.6% in the guselkumab arm. The percentage resolution for dactylitis from baseline to week 24 was 17.4% in the placebo arm compared with 55.2% in the guselkumab arm.
Two percent of patients in the placebo arm achieved minimal disease activity at week 24 compared with 23% in the guselkumab arm.
Guselkumab is a human monoclonal antibody designed to target IL-23. It was well-tolerated among patients with PsA, with no unexpected safety findings across the patient population. The investigational drug is currently undergoing a phase 3 development program for psoriatic arthritis.
Within both arms, patients who experienced less than 5% improvement from baseline in swollen and tender joints by week 16 qualified for early escape and switch to open-label therapy with ustekinumab. The remaining patients who received placebo were switched to the guselkumab arm at week 24.
The findings were presented at the Annual European Congress of Rheumatology.