The New England journal of medicine 2023 Oct 05
Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper.
Abstract
Background
More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway.
Methods
In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the 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.
Results
A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). 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%).
Conclusions
Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.).
Related Questions
What characteristics make a PMR patient a good candidate for sarilumab?
As rheumatologists, we are familiar with sarilumab, so we may already be comfortable using this medication. It has a role to play in managing patients with some of the following issues: Those who are struggling with early steroid tapers, i.e., not successfully tapering from 10 down to 5 mg/qd. Pati...
What baseline and ongoing testing do you recommend for patients with PMR who are going to be on a prolonged steroid taper?
My answer below is specific to patients with a definite diagnosis of PMR and does not necessarily cover diagnostic testing such as evaluation for possible mimics, which is certainly important and should include infections and malignancy in main differential, or other rheumatic diseases (RA, GCA). Va...
At what point do you consider a patient to have relapsing PMR?
Relapses in PMR are quite common. It is not unusual for patients to do well initially and as steroids are tapered, they start to describe a recurrence of symptoms. My concern is when these relapses occur early. For example, if they are noted as a patient tapers down from 10 mg towards 5 mg/day and r...
How will you adjust your approach to steroid taper in patients with PMR also on sarilumab?
I would try to replicate the prednisone taper followed in the SAPHYR study that weaned patients off over 14 weeks, understanding that there may be patients that won’t be able to taper the prednisone so aggressively or may benefit, in the opinion of the treating physician, from longer tapers (e.g., 4...
How will you approach tapering sarilumab in patients with PMR in remission?
Unfortunately, there is no data at the moment to inform decisions about the optimal duration of sarilumab treatment for PMR patients and how to discontinue this medication. The clinical trial that demonstrated efficacy was limited to 12 months and the drug was stopped altogether after that period. N...
How will you approach drug sequencing in patients with PMR given the SAPHYR data?
The SAPHYR study enrolled patients with PMR who relapsed while tapering prednisone at daily doses equal to or greater than 7.5 mg. One group of patients received sarilumab 200 mg every 2 weeks along with a 14-week prednisone taper and another group of patients received a placebo along with a 52-week...