Long-term sarilumab demonstrates no new safety concerns in rheumatoid arthritis
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Long-term sarilumab therapy for rheumatoid arthritis demonstrates no new safety outcomes regardless of concurrent use of conventional synthetic disease-modifying antirheumatic drugs, according to data published in Rheumatology.
“Sarilumab is a human recombinant IgG1 monoclonal antibody that binds to both soluble and membrane-bound IL-6 receptors (IL-6R) to inhibit IL-6-mediated signaling,” Gerd Burmester, MD, professor of medicine and clinical researcher at Charité University Hospital, in Berlin, and colleagues wrote.
“Although the efficacy and safety of sarilumab as monotherapy or in combination with [conventional synthetic DMARDs (csDMARDs)] have been demonstrated in phase III randomized controlled trials (RCTs), that are active comparator- and placebo-controlled in adults with active RA, its use in a chronic disease, such as RA, necessitates long-term evaluation of its safety and efficacy,” they added.
To investigate sarilumab (Kevzara, Sanofi) as a long-term therapy in patients with RA, Burmester and colleagues analyzed data from the phase 2/3 EXTEND and phase 3 MONARCH open-label extensions. These extensions included patients from six randomized trials. EXTEND included patients with RA aged 18 years or older who had failed two or fewer TNF antagonists, and had demonstrated an inadequate response to, or were intolerant of, TNF inhibitors. Patients in MONARCH, meanwhile, were aged 18 years and older and were not considered as viable patients for therapy with methotrexate.
Patients in EXTEND had been randomized to receive either sarilumab monotherapy or combination therapy with sarilumab plus conventional synthetic DMARDs, while the MONARCH extension included continuation and switch groups. Patients in both trials received sarilumab every 2 weeks for at least 264 weeks and up to 516 weeks, for EXTEND, or for 276 weeks in MONARCH.
The primary outcome of the current analysis was the long-term safety of sarilumab in patients receiving, and not receiving, conventional synthetic DMARDs. The researchers evaluated the occurrences of treatment-emergent adverse events, events of special interest, the presence of sarilumab antibodies and laboratory changes. They additionally used the Medical Outcomes Survey Short Form 36 to assess certain groups of patients.
Those who received sarilumab monotherapy included the 111 patients the “sarilumab monotherapy” group, the 165 patients in the “continuation” group, and the 155 patients in the group “switch” group who received placebo before switching to sarilumab. Meanwhile, 1,910 patients received sarilumab alongside conventional synthetic DMARDs.
According to the researchers, the incidence rates for one or more treatment-emergent adverse events were 126 per 100 patient-years in the “sarilumab monotherapy” group, 169 per 100 patient-years in the combination group, 159 per 100 patient-years in the “continuation” group and 159 per 100 patient-years in the “switch” group. The most common adverse event was neutropenia. Adverse events of special interest were rare, and included malignancy and major cardiovascular events, the researchers wrote.
“Long-term treatment with sarilumab with or without background csDMARDs in patients with RA identified no new safety signals,” Burmester and colleagues wrote. “The results are consistent with IL-6 signaling blockade and confirm the safety profile of sarilumab from the phase III RCTs.”
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