Novel Rheumatoid Arthritis Therapy Effective in Phase 3 Study

New drug could serve as a potential treatment option for patients who have shown an inadequate response to conventional disease-modifying drugs.

An investigational therapy proved effective in treating patients with rheumatoid arthritis (RA) who have shown an inadequate response to conventional disease-modifying drugs, according to results from a phase 3 trial.

The study, published in The Lancet, assessed the efficacy of upadacitinib in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Upadacitinib, a selective inhibitor of the enzyme Janus kinase 1 (JAK1), works by disrupting the signaling pathway responsible for triggering inflammatory responses, according to the study.

The study was conducted across 150 sites in 35 countries and included 661 patients. Enrolled patients were 18 years of age and older with active RA for 3 months or longer who had received csDMARDs for at least 3 months with a stable dose for at least 4 weeks before study entry.

Patients had an inadequate response to at least 1 of the following csDMARDs: methotrexate, sulfasalazine, or leflunomide. The primary endpoints were the proportion of patients at week 12 who achieved 20% improvement in American College of Rheumatology criteria (ACR20) and a 28-joint disease activity score using C-reactive protein of 3·2 or less.

Patients received either a once-daily extended-release formulation of upadacitinib 15 mg or 30 mg, or a placebo for 12 weeks. After 12 weeks, patients taking a placebo received 15 mg or 30 mg of upadacitinib once daily.

Sixty-four percent of patients treated with upadacitinib 15 mg and 66% of patients receiving upadacitinib 30 mg achieved ACR20 at week 12, compared with 36% of patients receiving a placebo.

Overall, patients treated with upadacitinib showed significant improvements in joint swelling compared with patients who received a placebo. These patients also experienced less pain and showed improvements in joint function.

Adverse events were reported in 57% of patients administered upadacitinib 15 mg, 54% of patients administered upadacitinib 30 mg, and 49% of patients given a placebo. The most commonly reported adverse events in the trial were nausea, nasopharyngitis, upper respiratory tract infection, and headache.

“Our results prove that JAK inhibitors represent an effective treatment alternative in patients with long-term conditions who do not respond adequately to conventional drugs, and in those for whom biologics are not a good treatment option,” Gerd-Rüdiger Burmester, MD, head of Charité’s Medical Department, Division of Rheumatology and Clinical Immunology, said in a press release. “JAK inhibitors could help these patients achieve a quick response to treatment, allowing them to gain control over their illness.”

References

Othman AA, Pangan AL, Camp HS, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomized, double-blind, placebo-controlled phase 3 trial. The Lancet. 2018. DOI:https://doi.org/10.1016/S0140-6736(18)31115-2

Drug successful in phase 3 clinical trial [news release]. Charité Universitätsmedizin Berlin website. https://www.charite.de/en/service/press_reports/artikel/detail/aussicht_auf_neue_therapie_bei_rheumatoider_arthritis/. Accessed August 24, 2018.