medwireNews: Phase 3 SAPHYR study findings suggest that the interleukin (IL)-6 receptor inhibitor sarilumab with glucocorticoid taper is an efficacious treatment option for patients with steroid-resistant polymyalgia rheumatica (PMR).
“Interleukin-6 plays a key role in PMR,” Bhaskar Dasgupta (Anglia Ruskin University, Cambridge, UK) told delegates at the EULAR 2022 Congress in Copenhagen, Denmark, in the late-breaking abstract session.
“We know that IL-6 inhibition results in decrease in disease symptoms, it increases remission rates, and decreases inflammation and cumulative steroid dosage.”
The researchers investigated sarilumab’s efficacy and safety in relapsing PMR in a trial involving 117 patients aged 50 years or older (median 69–70 years) with active PMR who had a median of two disease flares while taking at least 7.5 mg/day of prednisone or equivalent. The majority of patients were women (63.8–75.0%), the median duration of PMR was 292–310 days, and many of the patients had received prior immunosuppression.
The participants were randomly assigned to receive 52 weeks of treatment with sarilumab 200 mg every 2 weeks in addition to 14 weeks of glucocorticoid tapering or placebo every 2 weeks with 52 weeks of glucocorticoid tapering.
The findings showed that the 59 patients in the sarilumab treatment arm were significantly more likely to achieve sustained remission at 52 weeks than the 58 patients given placebo, at rates of 28.3% versus 10.3%.
Sustained remission was defined as disease remission by week 12, absence of disease flare and normalization of C-reactive protein (CRP) levels from weeks 12 to 52, and adherence to the per-protocol glucocorticoid taper regimen from weeks 12 to 52.
Dasgupta noted that the significant improvement in sustained remission with sarilumab versus placebo was maintained when the CRP normalization requirement was removed, at 31.7% versus 13.8%.
He also reported that sarilumab benefit extended to all of the individual components of sustained remission. Specifically, 46.7% of sarilumab-treated patients achieved disease remission by week 12 compared with 37.9% of placebo-treated patients and they were more likely to be free from disease flares after week 12 (55.0 vs 32.8%), to have sustained CRP normalization (66.7 vs 44.8%), and successfully adhere to glucocorticoid tapering (50.0 vs 24.1%).
Other significant improvements in secondary endpoints with sarilumab versus placebo included a longer time to first PMR flare and less glucocorticoid use (mainly due to reduced flares).
Dasgupta particularly highlighted the “major” treatment differences in patient-reported outcomes, which he said are “exciting,” because “we know from our previous studies [that] patient-reported outcomes in terms of PMR and quality of life are actually lower at onset than what we see with rheumatoid arthritis.”
Notably sarilumab treatment was associated with significant improvements in general quality of life, short form-36 mental and physical components, and fatigue, as well as changes on the HAQ-DI (borderline significance), pain on the visual analog scale, and PMR activity scores.
“We think that this improvement in the [patient-reported outcomes] that we saw in this study may directly relate to the inhibition of IL-6,” remarked Dasgupta.
Treatment-emergent adverse events (TEAEs) were numerically, but not significantly, higher among patients taking sarilumab, at 94.9% compared with 84.5% in the placebo arm, primarily due to the presence of neutropenia (15.3%), “which is a well-known side effect of a known adverse effect of IL-6 inhibition,” Dasgupta explained.
Counterintuitively, the risk for serious TEAEs was higher among those taking placebo, at 20.7% compared with 13.6% for those taking sarilumab.
“In particular, we did not find any unexpected serious [TEAEs] outside the safety profile of sarilumab,” confirmed Dasgupta.
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EULAR 2022; Copenhagen, Denmark: 1–4 June
Ann Rheum Dis 2022; 81: 210–211