乌鸦传媒

Secukinumab (Cosentyx) did not demonstrate superiority compared with adalimumab (Humira) in the first head-to-head study of these agents in psoriatic arthritis (PsA), a researcher reported at the .

In a phase IIIb trial that included 853 patients using multiple imputation analysis, secukinumab did not reach statistical significance over adalimumab on the primary endpoint of a 20% improvement on the criteria of the American College of Rheumatology (ACR20), said Iain McInnes, MD, PhD, of the University of Glasgow in Scotland and EULAR's current president. At week 52, ACR20 responses were seen in 67.4% of patients randomized to secukinumab, and 61.5% of those receiving adalimumab (OR 1.30, 95% CI 0.98-1.72, P=0.0719).

However, he said, in a prespecified sensitivity analysis using nonresponder imputation, ACR20 responses were seen in 66.9% of patients in the secukinumab group compared with 59.5% of those in the adalimumab group (OR 1.38, 95% CI 1.04-1.83, P=0.0239).

Secukinumab is an inhibitor of interleukin (IL)-17A that has shown efficacy in multiple domains of PsA, including , while adalimumab is a tumor necrosis factor (TNF) inhibitor widely used as a first-line biologic in PsA.

"There are limited data to support physicians in deciding which treatment to use for patients with psoriatic arthritis who have had an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs, but we have head-to-head trials showing that IL-17A inhibitors have higher efficacy than TNF inhibitors in moderate-to-severe psoriasis and in the skin manifestations of patients with PsA," McInnes said.

"However, comparative data are relatively few on the efficacy of these agents on the musculoskeletal manifestations of PsA," he added.

Therefore, to investigate whether secukinumab monotherapy was superior to adalimumab monotherapy through 52 weeks in biologic-naive patients with active PsA, the international research team conducted the study known as EXCEED, which randomized patients to subcutaneous secukinumab, 300 mg every 4 weeks, or subcutaneous adalimumab, 40 mg every 2 weeks.

The baseline characteristics of the two groups were broadly similar. Mean age was 49, disease duration averaged 5 years, and slightly more patients in the secukinumab group were women.

Mean baseline Psoriasis Area and Severity Index (PASI) was 10, tender joint count was 20, and swollen joint count was 10. The average score on the the Health Assessment Questionnaire-Disability Index (HAQ-DI) was 1.3, and the mean score on the Disease Activity Score in 28 joints was 4.7. Slightly more patients (61.8% vs 54.9%) in the adalimumab group had enthesitis at baseline.

With regard to secondary endpoints, McInnes said that "since superiority was not established for the primary endpoint, additional endpoints in the statistical hierarchy were not formally tested for statistical significance."

Nonetheless, he reported that for the endpoint of a 90% improvement on the PASI, there were numerically greater responses with secukinumab (65.4% vs 43.2%, OR 2.49, 95% CI 1.67-3.71, P<0.0001).

On the ACR50 response, the two groups were similar, "with some numerical advantage at week 52 for secukinumab," he noted (49% vs 44.8%, OR 1.18, 95% CI 0.90-1.55, P=0.2251).

In addition, similar results were seen for the two groups in mean change from baseline on the HAQ-DI: -0.58 in the secukinumab group and-0.56 in the adalimumab group, and in resolution of enthesitis, reported in 60.5% and 54.2%, respectively.

Higher retention rates also were seen for secukinumab on a Kaplan-Meier analysis of time to discontinuation.

Safety was broadly consistent with previous reports for each of the agents, McInnes said. Infections were reported in 56% of the secukinumab group and 55% of the adalimumab group, serious infections in 2% and 1%, respectively, and Candida infections in 4% and 2%.

Comment