medwireNews: The interleukin (IL)-6 inhibitor sirukumab could offer a therapeutic option for patients with active rheumatoid arthritis (RA) despite treatment with disease-modifying antirheumatic drugs (DMARDs), results of the phase III SIRROUND-D study suggest.
Unlike IL-6 receptor blockers, including tocilizumab and sarilumab, “sirukumab is a human monoclonal antibody that selectively binds to the IL-6 cytokine,” explain the researchers in the Annals of the Rheumatic Diseases.
Paul Tak (GlaxoSmithKline Research and Development, Stevenage, UK) and study co-authors randomly assigned 1670 participants to receive treatment with subcutaneous sirukumab at a dose of either 100 mg every 2 weeks or 50 mg every 4 weeks, or placebo. Participants in the placebo group who did not have a 20% improvement from baseline at week 18 or 40 in swollen and tender joint counts were crossed over to one of the sirukumab arms.
At the 16-week follow-up, a significantly greater proportion of the 557 patients receiving sirukumab 100 mg and the 557 receiving sirukumab 50 mg achieved at least a 20% improvement in ACR criteria (ACR20) compared with the 556 patients in the placebo group, at 53.5% and 54.8% versus 26.4%.
And participants receiving sirukumab experienced significantly less radiographic progression over 52 weeks than those receiving placebo, with mean changes from baseline in modified Sharp/van der Heijde scores of 0.46, 0.50, and 3.69 points for the 100 mg, 50 mg, and placebo groups, respectively.
The team also observed significant improvements in disability at week 24, and in physical and emotional health scores at week 52, among patients receiving either dose of sirukumab versus placebo.
The most common adverse event that occurred over 52 weeks of treatment with sirukumab was an increase in alanine aminotransferase, affecting 17.1% of sirukumab-treated patients versus 4.5% of those in the placebo group, followed by an increase in aspartate aminotransferase (10.6 vs 3.4%), upper respiratory tract infection (9.9 vs 11.3%), and injection site erythema (9.8 vs 1.1%).
At week 18, 4.7% of patients in the sirukumab 100 mg group, 2.9% of patients in the 50 mg group, and 3.1% of those in the placebo group experienced serious adverse events (SAEs), with a corresponding 9.8%, 11.0%, and 6.8% of participants having SAEs at the 52-week follow-up.
“The safety profile of sirukumab did not raise any new concerns and was consistent with those reported for agents targeting the IL-6 receptor,” summarize the researchers.
However, they caution that the trial design “led to loss of randomisation after the 18-week pure placebo-controlled period,” resulting in longer total exposure to sirukumab relative to placebo, and therefore confounding the interpretation of safety comparisons between sirukumab- and placebo-treated patients.
Tak and colleagues also note that the trial “included a population of patients with RA who were refractory to DMARDs and who may or may not have received prior biological therapy,” meaning that the results are “not applicable to the full spectrum of patients with RA.”
Nonetheless, they conclude that the SIRROUND-D results “provide important information on the use of anti–IL-6 therapy as a possible first-line or alternate biological therapy in patients who are no longer responding to conventional DMARDs.”
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