Cosentyx Slightly Better Than NSAIDs in Reducing Disease Progression, Data Analysis Shows

While both Cosentyx (secukinumab) and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to reduce disease progression in people with ankylosing spondylitis, analysis of trial data shows that the anti-rheumatic therapy worked slightly better over a two-year period.

However, while Cosentyx did a somewhat better job in stopping spinal disease progression, the difference was not enough to reach statistical significance, the study showed.

The findings, “Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison,” were published in Arthritis Research & Therapy.

Ankylosing spondylitis (AS) is a debilitating type of arthritis that mainly affects the joints of the spine, causing chronic pain and lifelong physical disability. Treatment options — including medications to reduce inflammation, physical therapy, and surgery — usually focus on minimizing pain and delaying or preventing disease progression.

Cosentyx is a disease-modifying anti-rheumatic drug (DMARD) developed by Novartis that has been approved for the treatment of people with AS. Its active ingredient, the antibody secukinumab, was designed to bind to interleukin-17A (IL-17A), a molecule that regulates immune and inflammatory responses in the body.

By binding to IL-17A, secukinumab prevents it from interacting with its receptor, the IL-17 receptor. That interrupts the signaling cascade that triggers tissue inflammation, which ultimately reduces disease progression.

A randomized, double-blind, placebo-controlled Phase 3 MEASURE 1 trial (NCT01358175) showed that treatment with Cosentyx significantly improved the signs and symptoms of AS patients over two years. Its open-label extension study (NCT01863732) showed the same results for up to four years.

Meanwhile, other studies found that NSAIDs, a class of anti-inflammatory drugs, also reduced the signs and symptoms of AS.

“Although there is some evidence for a potential benefit of NSAIDs in decelerating radiographic progression in AS, when administered continuously, there are no data published to date from prospective, randomized, and controlled studies with anti-TNF [tumor necrosis factor] treatments demonstrating inhibition of spinal radiographic progression in AS,” the investigators said.

To learn more, researchers compared disease progression in a group of AS patients treated with Cosentyx for up to two years in the MEASURE 1 trial, with that of another group of AS patients treated with NSAIDs in the ENRADAS trial (NCT00715091) for up to two years.

Disease progression was assessed based on spine radiographs obtained at the beginning of the trials (baseline), and after two years of treatment. The radiographs were scored by two independent readers based on the modified stoke ankylosing spondylitis spinal score (mSASSS). Those scores assess radiographic progression in AS, and correlate with worsening measures of disease symptoms, spinal mobility, and physical function.

The study’s primary endpoint, or goal, was to determine the percentage of patients showing no disease progression — an mSASSS change from baseline, to the end of the treatment, lower than zero. The primary analysis set included patients who had taken spine radiographs at baseline (within the first 30 days of the trial), and post-baseline (between days 31 and 743).

Sensitivity analyses also were performed to evaluate the robustness of the comparisons between the two groups. These included two sets of analyses: the first included all patients who had taken spine radiographs at baseline (within the first 30 days of the trial) and after two years of treatment (between day 640 and 819); the second included all patients who had taken spine radiographs at baseline and post-baseline.

A total 168 patients (84%) from MEASURE 1, and 69 (57%) from ENRADAS, were eligible for inclusion in the primary analysis set.

Results showed that, among those who qualified for the primary analysis set and for all sensitivity analyses, the mean changes from baseline to the end of the treatment period in the mSASSS were lower among patients who participated in MEASURE 1, compared with those who participated in ENRADAS.

In addition, researchers found the percentage of patients showing no signs of disease progression was consistently higher among those who participated in MEASURE 1, regardless of the cut-off value selected for the mSASSS change from baseline.

However, these differences were not sufficient to reach statistical significance.

“The key findings of this analysis showed that over 2 years, secukinumab [Cosentyx]-treated patients demonstrated a numerically higher proportion of radiographic non-progressors and a numerically, but statistically non-significant, lower change in mSASSS compared with biologic-naïve NSAID-treated patients in the primary analysis set,” the researchers said.

“Further research is needed to understand the impact of IL-17A inhibition with secukinumab on spinal disease progression in AS patients. [I]t can be expected that SURPASS (NCT03259074), an ongoing head-to-head study powered to compare differences in spinal radiographic progression with secukinumab compared with biosimilar adalimumab, will help to address this,” they added.