Secukinumab, Adalimumab Show Similar Efficacy for Enthesitis Resolution in Patients With Psoriatic Arthritis at 52 Weeks

In a post hoc analysis of the EXCEED study, researchers found that secukinumab and adalimumab—two biologic disease-modifying antirheumatic medications (bDMARDs)—showed similar efficacy in the resolution of enthesitis at 52 weeks.

Enthesitis is an inflammation specifically located where a tendon or ligament inserts into bone—known as the entheses. Enthesitis occurs in anywhere from 35% to 50% of patients with psoriatic arthritis (PsA).

The European Alliance of Associations for Rheumatology guidelines recommend biologic disease-modifying antirheumatic drugs (bDMARDs) for those with enthesitis who either cannot tolerate non-steroidal anti-inflammatory drugs or do not experience relief from them. But clinicians lack guidance on which specific bDMARDs to offer this patient population. Two potential options are secukinumab, a human monoclonal antibody that selectively neutralizes IL-17A for the treatment of PsA, and adalimumab, a tumor necrosis factor inhibitor, which is a mainstay of PsA treatment.

The EXCEED study was a multicenter, randomized, double-blind, active-controlled, parallel-group phase 3 trial that compared secukinumab and adalimumab in patients with PsA and active psoriasis who were also naïve to bDMARDs.

In the EXCEED study, the primary endpoint—superiority of American College of Rheumatology 20% improvement criteria response at week 52 when comparing secukinumab to adalimumab—was not met. But researchers did find efficacy when examining several musculoskeletal endpoints, including resolution of enthesitis at week 52. However, a detailed analysis was not performed at the time of the EXCEED study, and so the authors performed a post hoc analysis.

“This study aims to provide detail on enthesitis treatment response, including temporal response and site-specific enthesitis data along with additional enthesitis assessments, in patients with PsA treated with secukinumab or adalimumab over 52 weeks in EXCEED,” the authors wrote.

In the post hoc analysis, researchers grouped the patient data originally from the EXCEED study by those who had or did not have baseline enthesitis based on two indexes: the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC).

The study included all patients from the EXCEED study who completed 52 weeks of treatment (n = 853). Of the total patients assessed by LEI (n = 851), 498 (58.5%) had enthesitis at baseline. Of the total patients assessed by SPARCC (n = 853), 632 (74.1%) had enthesitis at baseline.

The researchers assessed the mean change from baseline in LEI and SPARCC enthesitis counts at weeks 24 and 52. They found that both secukinumab and adalimumab offered similar improvements at both timepoints. At week 24, for patients receiving secukinumab, the mean change from baseline in the LEI enthesitis count was -1.6, while the mean change in the SPARCC enthesitis count was -3.3. For patients receiving adalimumab at the same timepoint, the LEI and SPARCC counts showed similar improvements: −1.6 and −3.1, respectively.

At week 52, the mean change from baseline in LEI and SPARCC enthesitis counts for patients receiving secukinumab was −1.8 and −3.6, respectively. For those receiving adalimumab at the same timepoint, the LEI and SPARCC improvement was −2.1 and −3.9, respectively.

Another notable finding was that patients in both treatment groups achieved enthesitis resolution at similar proportions. By week 24, 49.6% of patients assessed by LEI who received secukinumab achieved enthesitis resolution. That number reached 45.8% for patients assessed by SPARCC at the same timepoint. For those who received adalimumab, 43.6% of those assessed by LEI and 43.5% of those by SPARCC achieved enthesitis resolution.

Through week 52, 60.7% and 53.2% of patients receiving secukinumab and 55.3% and 51.4% of patients receiving adalimumab achieved resolution as measured by LEI and SPARCC, respectively.

“Overall, the findings from this study indicate that secukinumab and adalimumab improve enthesitis among patients with PsA to a similar extent in terms of achievement of enthesitis resolution, timing of response, site-specific responses and occurrence of relapse after first resolution. Our findings suggest that inhibition of IL-17A with secukinumab can result in improvements over 52 weeks in enthesitis responses comparable to those achieved with adalimumab among patients with PsA.”

Reference:

Kaeley GS, Schett G, Conaghan PG, et al. Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study. Published online April 25, 2023. Rheumatology (Oxford). doi:10.1093/rheumatology/kead181