Cosentyx Effective in Active nr-axSpA, Phase 3 PREVENT Trial Shows
These findings were the basis for Cosentyx’s recent approval in the U.S. The treatment is also indicated for the treatment of ankylosing spondylitis, the other form of axSpA, in the U.S. and the European Union.
The results of the PREVENT trial, “Secukinumab improves signs and symptoms of non‐radiographic axial spondyloarthritis: primary results of a randomized controlled phase III study,” were published in the journal Arthritis & Rheumatology.
The hallmark of axSpA is inflammation of the joints where the base of the spine meets the pelvis. Cosentyx, developed by Novartis, is a monoclonal antibody that blocks interleukin-17a, a pro-inflammatory immune protein implicated in chronic inflammatory diseases.
In two pivotal Phase 3 clinical trials — MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375) — Cosentyx was able to significantly ease symptoms in patients with ankylosing spondylitis. Notably, axSpA is called ankylosing spondylitis when joint damage is visible on regular X-rays of the spine and nr-axSpA when no such damage can be seen.
The purpose of the Novartis-sponsored PREVENT trial (NCT02696031) is to test the safety and efficacy of Cosentyx in active nr-axSpA. It is an ongoing Phase 3 study testing Cosentyx over two years, with an extension period of up to two more years.
The trial involved 555 adults with a mean age of about 39 years. Most participants were men. Patients had been treated with at least two non-steroidal anti-inflammatory drugs for up to four weeks. A subset included people who failed to show a good response to a TNF inhibitor therapy, but most trial participants (90.3%) had not received any TNF inhibitors (treatment-naïve).
Switching from a placebo to Cosentyx or standard care with a TNF inhibitor was permitted after week 20, based on an assessment by investigators and the patient.
This study’s primary goal was to assess whether Cosentyx was superior to placebo in TNF inhibitor-naïve patients, as measured by the proportion of those who met the Assessment of Spondyloarthritis International Society (ASAS) 40 response criteria at weeks 16 and 52 (one year).
ASAS40 is defined as an improvement or reduction of at least 40% in a minimum of three of the following domains: inflammation, global patient assessment, pain, and function, as assessed with the Bath Ankylosing Spondylitis Functional Index.
Overall, 481 patients completed one year of treatment. The proportion of participants who switched to Cosentyx or a TNF inhibitor after week 20 was about 50% in those who received Cosentyx (with or without induction phase), and 64% in the placebo group. Three patients elected to switch to a TNF inhibitor.
The ASAS40 response in TNFi-naïve patients was significantly higher in the Cosentyx induction group compared to the placebo at week 16 (41.5% vs. 29.2%), and also significantly greater with Cosentyx without the induction phase at one year in comparison to the placebo (39.8% vs. 19.9%).
When switching to Cosentyx, 16% of patients in the induction group and 24.4% of those in the non-induction group achieved ASAS40, compared to 10.9% in the placebo group.
The trial’s secondary goals included a reduction in disease activity as determined by the Bath AS Disease Activity Index (BASDAI), which measures fatigue, spinal pain, joint pain or swelling, inflammation, and morning stiffness.
At week 16, the total BASDAI score was significantly improved (lower) with Cosentyx compared to the placebo group. These improvements were seen as early as the first week of treatment.
At one year, the proportion of patients with a BASDAI score that decreased by half from baseline was above 30% with Cosentyx and 19.9% with the placebo.
A significant reduction in swelling where the base of the spine meets the pelvis was found by MRI at week 16 in patients treated with Cosentyx.
Additional assessments, including of health-related quality of life with the Ankylosing Spondylitis Quality of Life questionnaire, also found significant benefits with Cosentyx at week 16.
Safety results were consistent with previous clinical trials, and no new safety concerns were reported. Here, the overall incidence of adverse effects (AEs) up to week 20 was 61.2% for Cosentyx compared to 54.3% in the placebo group. Most reported AEs were mild to moderate.
Nine mild to moderate cases of an eye inflammatory condition called uveitis were reported in the treatment groups compared to two cases in the placebo group. Inflammatory bowel disease was reported in seven treated patients and none in the placebo group.
“In conclusion, [Cosentyx] 150 mg demonstrated rapid and significant improvement in the signs and symptoms of nr-axSpA in both TNFi-naïve patients and the overall study population by Week 16, which was sustained through Week 52,” the researchers wrote.
“The PREVENT study results, combined with the results from the MEASURE program … demonstrate that [Cosentyx] can be a viable option to treat the entire spectrum of axSpA i.e., from early to late stage or from nr-axSpA to [ankylosing spondylitis],” they added.