Cosentyx Reduces Disease Activity and Pain in nr-axSpA Patients, Phase 3 Trial Shows

Treatment with Cosentyx (secukinumab) provided stable reduction in disease activity, as well as less pain and better mobility in people with non-radiographic axial spondyloarthritis (nr-axSpA), a Phase 3 trial shows.

Atul Deodhar, MD, the study’s lead investigator, presented the research in a session, “Secukinumab 150 mg Significantly Improved Signs and Symptoms of Non-radiographic Axial Spondyloarthritis: Results from a Phase 3 Double-blind, Randomized, Placebo-controlled study,” at the 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting, held in Atlanta.

Axial spondyloarthritis is a type of arthritis that predominantly affects the joints of the spine, leading to chronic pain and lifelong physical disability. It is called ankylosing spondylitis if joint damage is visible through radiographs (X-rays), or nr-axSpA when joint damage is not visible on plain-film radiographs.

Cosentyx, developed by Novartis, is a monoclonal antibody that blocks interleukin-17a, a pro-inflammatory molecule. This is intended to prevent the increased inflammation and immune reactions that occur in chronic inflammatory diseases.

The safety and efficacy of Cosentyx is being tested in a Phase 3 trial called PREVENT (NCT02696031).

The Novartis-sponsored study recruited 555 adults with active nr-axSpA that had received treatment with a minimum of two non-steroidal anti-inflammatory drugs for up to four weeks. They may also have previously shown an inadequate response to a TNF inhibitor therapy. Most (90.3%) had not undergone any biologic treatments.

Participants were randomly assigned to either Cosentyx given subcutaneously (under the skin) as a 150 mg monthly dose, with or without an induction phase (150 mg administered weekly for four weeks), or to a placebo.

The study’s primary goal was to assess Cosentyx’s efficacy, as measured by the proportion of patients who met the Assessment of Spondyloarthritis International Society response criteria at weeks 16 and 52. This is defined as an improvement of at least 40% and an increase of at least 10 units (on a 0 to 100 scale) in a minimum of three of the following domains: patient global assessment, pain assessment, function (Bath Ankylosing Spondylitis Functional Index), and inflammation.

Secondary goals included reductions in disease activity as measured by other tools, including the Bath AS Disease Activity Index (BASDAI). This is a test of fatigue, spinal pain, joint pain or swelling, inflammation of the entheses (where tendons or ligaments insert into the bone), and morning stiffness.

In line with prior reports, results at week 16 showed that significantly more patients receiving Cosentyx after an induction phase had a clinically meaningful reduction in disease activity — 42.2% — compared with those receiving the placebo (29.2%). These improvements continued through week 52 (one year) of treatment.

Cosentyx also led to significant benefits in secondary outcomes including pain, mobility, and health-related quality of life. Patients treated with Cosentyx showed a reduction in BASDAI score of 2.4 points, compared with 1.5 points in the placebo group.

Safety results were consistent with previous data, and no new safety concerns were identified. Researchers registered three cases of serious infections and one of Crohn’s disease in participants treated with Cosentyx.

“The PREVENT study showed clinically significant outcomes as early as week three, and these were maintained up to one year for patients treated with Cosentyx,” Deodhar, medical director of rheumatology clinics at Oregon Health & Science University, said in a press release.

PREVENT is the largest study of a biologic therapy in people with nr-axSpA, according to Novartis. It is a two-year study expected to conclude in December 2020.

Cosentyx is already approved for adults with ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

“These data strengthen the evidence for Cosentyx as a treatment option that addresses the complete axSpA disease spectrum,” said Eric Hughes, the global development unit head of Immunology, Hepatology & Dermatology at Novartis.

Based on these 16-week findings, Novartis has submitted an application for the approval of Cosentyx for nr-axSpA to the European Medicines Agency. Results at one year of treatment will be used to support a similar request in the U.S.

“Non-radiographic axial spondyloarthritis [nr-axSpA] can have a debilitating symptom burden, and if approved, this would be a welcome addition to the limited treatment options currently available to treat this condition,” added Deodhar.