medwireNews: Sarilumab treatment provides consistent benefits for a broad range of patients with rheumatoid arthritis (RA), suggests a subgroup analysis of data from phase 3 trials.
The study by Mark Genovese (Stanford University School of Medicine, Palo Alto, California, USA) and colleagues included participants from three trials, all of which previously demonstrated significant benefits with sarilumab versus comparator treatments over 24 weeks.
MOBILITY investigated sarilumab 150 mg or 200 mg every 2 weeks versus placebo alongside ongoing methotrexate, while TARGET evaluated the same doses of sarilumab versus placebo alongside conventional DMARDs, and MONARCH compared sarilumab monotherapy (200 mg every 2 weeks) with adalimumab monotherapy. MOBILITY and MONARCH involved participants with prior methotrexate exposure, while TARGET included those with an inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors.
In the current subgroup analysis, Genovese and team found “generally consistent” benefits with sarilumab in terms of ACR response rates, CDAI- and DAS-based endpoints, and radiographic progression when patients were categorized by age, sex, race, and region.
However, there was a significant interaction between baseline autoantibody status and sarilumab efficacy that remained consistent across most study endpoints. Greater benefits were seen among patients who were positive for anti-cyclic citrullinated peptide antibodies (ACPA) at baseline compared with ACPA-negative individuals, particularly with the 200 mg dose.
There was also an interaction between BMI and treatment efficacy in the MONARCH study of sarilumab monotherapy, with participants with a BMI below the cutoff for obesity (<30 kg/m2) having “more robust sarilumab responses” than obese patients for a number of efficacy endpoints, report the investigators.
In the safety analysis, Genovese and colleagues report “no clear differences in the safety profile of sarilumab between patient subgroups,” with the exception of a higher risk for treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) among patients aged 65 years and over compared with younger patients.
For instance, in the sarilumab 200 mg arm of the MOBILITY study, 88.2% of the 51 patients aged 65 years and over experienced TEAEs, compared with 77.4% of the 345 younger patients. The corresponding TEAE rates in the placebo arm were 70.7% of 41 patients and 61.0% of 356 patients. Rates of SAEs in the sarilumab 200 mg group were 23.5% in the older patients compared with 9.6% in the younger patients; the corresponding SAE rates in the placebo arm were 9.8% and 4.8%.
“Safety and tolerability are a specific potential concern in this subpopulation, and AEs are among the main causes of discontinuation of RA therapy among older patients,” say the researchers in Arthritis Research & Therapy.
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