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Sarilumab for Relapse of Polymyalgia Rheumatica During Glucocorticoid Taper

In the Sarilumab in Patients with Polymyalgia Rheumatica (SAPHYR) trial, interleukin-6 blockade with the monoclonal antibody “showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering,” researchers report. “Patients … who received sarilumab plus a 14-week prednisone taper had a higher frequency of remission and lower glucocorticoid exposure than those who received placebo plus a 52-week prednisone taper.”

The phase 3 trial included 118 patients who were randomized to 52 weeks of a twice-monthly subcutaneous injection of either sarilumab 200 mg plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Based on a primary outcome of sustained remission at 52 weeks (resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52), the authors found these results: “At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P <0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%).”

Editorial: “Even with the growing evidence base from these trials, the future management of polymyalgia rheumatica continues to carry numerous questions that will keep the field busy,” an editorialist writes. “For example, it remains unclear which strategy is better: a step-down approach (i.e., the initiation of sarilumab or tocilizumab with a rapid glucocorticoid taper and a subsequent additional taper of the interleukin-6 receptor blocker) or a step-up approach (i.e., the addition of the interleukin-6 receptor blocker only after glucocorticoid therapy has been found to be insufficient). The best strategy will depend on the duration of sustained remission, on glucocorticoid-related side effects, and on drug expenses. Thus, the questions have been refined from ‘Can we manage?’ to ‘How do we manage?’ and from ‘Is glucocorticoid-free remission possible?’ to ‘How can we achieve glucocorticoid-free remission as fast as possible?’ Many factors will influence the choice of strategy and its consequent effects on the illness burden, degree of glucocorticoid exposure, burden of toxic effects, and relative cost-effectiveness.”

Source: New England Journal of Medicine