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07-05-2020 | Rheumatology | News | Article

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EXCEED: Similar musculoskeletal benefits with secukinumab vs adalimumab in PsA

Author:
Claire Barnard

medwireNews: Findings from the head-to-head EXCEED trial indicate that biologic-naïve patients with psoriatic arthritis (PsA) treated with secukinumab monotherapy do not experience greater musculoskeletal benefits than those given adalimumab.

This phase 3b study of adult patients with active PsA and an inadequate response or intolerance to conventional DMARDs “provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis,” write the investigators in The Lancet.

Iain McInnes (University of Glasgow, UK) and colleagues report that 67% of 426 participants who were randomly assigned to receive the interleukin (IL)-17A inhibitor secukinumab at a dose of 300 mg/week at weeks 0–4 and every 4 weeks thereafter achieved the primary endpoint of an ACR20 response at the 1-year follow-up.

This was not significantly different to the 62% response rate for the 427 patients who were instead given the tumor necrosis factor (TNF) inhibitor adalimumab 40 mg every 2 weeks.

Because the primary endpoint was not met, key secondary endpoints were not formally evaluated for statistical significance, but a higher proportion of patients treated with secukinumab versus adalimumab achieved a PASI90 skin response (65 vs 43%), and secukinumab-treated patients were more likely to achieve a simultaneous ACR50 and PASI100 response than those given adalimumab (31 vs 19%) in a prespecified exploratory analysis.

Moreover, treatment discontinuation rates were lower in the secukinumab compared with the adalimumab arm (14 vs 24%), with the main reasons for discontinuation being patient or guardian decision (5 vs 8%), adverse events (4 vs 7%), and lack of efficacy (4 vs 7%).

“The efficacy data in this study suggest that secukinumab was at least as efficacious as adalimumab in improving musculoskeletal endpoints, provided better responses on skin endpoints, and had a higher retention rate at week 52,” say McInnes and team, noting that their primary endpoint “directly addresses a key research question in psoriatic arthritis management, namely whether IL-17A or TNF inhibition [confers] musculoskeletal advantage.”

Writing in an accompanying comment, Merete Lund Hetland (Rigshospitalet, Glostrup, Denmark) agrees that “[t]he choice of a musculoskeletal primary endpoint […] was a strength of the study and reduced the effect of the cutaneous domain on interpretation of the results.”

However, she points out that the recommended secukinumab dose for biologic-naïve patients in routine practice “would be 150 mg rather than the 300 mg used in this trial,” and “it would have been interesting to see the performance of the lower dose.”

The EXCEED investigators say that “[n]o new safety signals were reported” in the trial, with treatment-emergent adverse events occurring in 77% of patients given secukinumab and 79% of those in the adalimumab group. Major adverse cardiac events and inflammatory bowel disease were each reported in two secukinumab-treated patients and none in the adalimumab group, while malignancies occurred in two and three patients, respectively.

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

Lancet 2020; 395: 1496–1505
Lancet 2020; 395: 1463–1465

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