ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.
Jeff Craven/MDedge News
Dr. Atul Deodhar
For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.
“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.
Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.
The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.
At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).
Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).
Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and –1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).
Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.
There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.
Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”
When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.
“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.
The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.
SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.