Sarilumab superior to placebo for achieving sustained remission in polymyalgia rheumatica
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Key takeaways:
- Patients were more likely to achieve sustained remission with sarilumab vs. placebo.
- The most common adverse event associated with sarilumab was neutropenia.
Among patients with polymyalgia rheumatica who relapse during glucocorticoid tapering, sarilumab is effective at enabling them to achieve sustained remission and lowering cumulative glucocorticoid use, according to data.
“Patients with polymyalgia rheumatica who have a relapse while tapering glucocorticoid therapy or have glucocorticoid-related adverse effects have limited treatment options,” Robert F. Spiera, MD, of the Hospital for Special Surgery, in New York, and colleagues wrote in the New England Journal of Medicine. “Thus, treatments that hasten disease remission, decrease symptoms, reduce overall dependence on glucocorticoids and the associated toxic effects, and improve quality of life and function are needed.”
To analyze the effectiveness of sarilumab (Kevzara, Sanofi) in patients with polymyalgia rheumatica, Spiera and colleagues conducted SAPHYR, a phase 3, multicenter, randomized, double-blind, placebo-controlled study. The researchers included patients with polymyalgia rheumatica who flared during glucocorticoid tapering in the 12 weeks leading up to enrollment.
Participants were additionally required to have a history of glucocorticoid use, demonstrate symptoms of polymyalgia rheumatica and have elevated C-reactive protein or erythrocyte sedimentation rates. Meanwhile, patients were excluded if they had ever received a diagnosis of giant cell arteritis, rheumatoid arthritis or another type of inflammatory arthritis.
Upon enrollment, patients were randomized 1:1 to receive 52 weeks of a twice-monthly injection of sarilumab 200 mg, plus 14 weeks of prednisone tapering, or placebo and 52 weeks of prednisone tapering. To manage adverse events and complications, patients receiving sarilumab could receive reduced doses every other injection.
The primary outcome at 52 weeks was sustained remission, defined as the achievement of clinical remission by week 12, with a lack of flares and sustained improvements in CRP and prednisone tapering adherence through 52 weeks. Key secondary endpoints included cumulative glucocorticoid dose through 52 weeks and the time until onset of first disease flare.
The analysis included 118 patients. Of those, 60 received sarilumab while 58 received placebo. After 52 weeks, 28% of patients receiving sarilumab and 10% of those receiving placebo achieved sustained remission. In addition, the median cumulative glucocorticoid dose at 52 weeks was “significantly lower” in the sarilumab group compared with those receiving placebo — 777 mg vs. 2,044 mg (P < .001).
According to the researchers, the most common adverse events in patients receiving sarilumab were neutropenia (15%), arthralgia (15%) and diarrhea (12%). Additionally, there was more treatment-related discontinuation in the group receiving sarilumab compared with the placebo group — 12% vs. 7%.
“In this phase 3 trial involving patients with polymyalgia rheumatica, significantly more patients had sustained remission at week 52 with sarilumab plus a 14-week prednisone taper than with placebo plus a 52-week prednisone taper,” Spiera and colleagues wrote. “The results of a sensitivity analysis that excluded acute phase reactants (ie, CRP and ESR) were consistent with the primary findings, which indicated that a reduction in CRP levels alone did not drive the observed effect with sarilumab.”
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