Secukinumab Improves Symptoms in TNF Inhibitor-Refractory Rheumatoid Arthritis

Patients with active rheumatoid arthritis (RA) who received 150 mg of secukinumab, an interleukin 17A (IL-17A) inhibitor, showed signs of clinical improvement and reduced disease activity at 24-week follow-up after having an inadequate treatment response to tumor necrosis factor inhibitors, according to results published in Arthritis & Rheumatology.

In a phase 3 study, Francisco J. Blanco, MD, PhD, from the Grupo de Investigacion Clinica and Instituto de Investigación Biomedica da Coruña-INIBIC at Hospital Universitario A Coruña in Spain, and colleagues performed a double-blind, randomized placebo-controlled study of 551 patients with active RA who received secukinumab, abatacept, or placebo. 

The patients who received abatacept at doses of <60 kg/500 mg, 60 to 100 kg/750 mg, and >100 kg/1000 mg and placebo were placed on the same intravenous and subcutaneous dosing schedule.

Patients in the secukinumab group received intravenous secukinumab (10 mg/kg) at baseline, 2 weeks, and 4 weeks, and received subcutaneous secukinumab (150 mg or 75 mg) at 4-week intervals up to 48 weeks. 

Researchers used 20% improvement according to American College of Rheumatology (ACR) criteria (ACR20) as a primary end point and 50% improvement according to ACR criteria (ACR50), 28-joint disease activity score with C-reactive protein (DAS28-CRP), and Health Assessment Questionnaire Disability Index (HAQ-DI) as secondary end points to measure clinical improvement.

At 24 weeks, 20.7% of patients in the 150-mg secukinumab group (P =.0305) and 28.3% of patients in the 75-mg secukinumab group (P =.0916) reached ACR20, whereas 42.8% of patients in the abatacept group and 18.1% of patients in the placebo grouped reached ACR20. Dr Blanco and colleagues found patients in the 150-mg secukinumab group had significantly improved DAS28-CRP scores (P =.0495) compared with the 75-mg secukinumab group. However, there were significant improvements in HAQ-DI and ACR50 scores in the secukinumab and placebo groups. The researchers also found an acceptable, similar safety profile in all patient groups.

Summary and Clinical Applicability

Dr Blanco and colleagues noted that although secukinumab was effective for patients with RA for whom anti-TNF therapy failed, clinicians should not consider IL-17A inhibition as a treatment option for these patients on its own because of a lack of incremental benefit to treatment.

“These data, along with data from phase 2 studies and those of other anti-IL-17A agents, suggest that IL-17A plays a lesser role in the pathogenesis of RA,” the researchers wrote. “This stands in contrast to the spondyloarthropathies including [psoriatic arthritis] and [ankylosing spondylitis] where IL-17A inhibition with secukinumab has demonstrated robust efficacy.”

Disclosures

This study was sponsored by Novartis Pharma AG.

Reference

Blanco FJ, Möricke R, Dokoupilova E, et al. Secukinumab in active rheumatoid arthritis: A randomized, double-blind placebo and active comparator controlled phase 3 study [published online February 19, 2017]. Arthritis Rheumatol. doi:10.1002/art.40070

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