Sarilumab Helps Achieve Sustained Remission during Glucocorticoids tapering in Polymyalgia Rheumatica

Polymyalgia rheumatica is a condition where more than half of patients experience relapse during the tapering of glucocorticoid therapy. A phase 3 clinical trial has shown that sarilumab, a human monoclonal antibody that blocks the interleukin-6 pathway, holds promise in treating polymyalgia rheumatica. This study was published in The New England Journal Of Medicine by Spiera R. and colleagues.

Previous research had suggested that blocking interleukin-6, an inflammatory cytokine, might be a viable approach in treating this condition. Sarilumab, a human monoclonal antibody, efficiently blocks the interleukin-6 pathway by binding to the interleukin-6 receptor α.

To investigate the potential of sarilumab in treating polymyalgia rheumatica, a phase 3 trial was conducted. The trial randomised patients in a 1:1 ratio into two groups: one receiving 52 weeks of a twice-monthly subcutaneous injection of sarilumab (at a dose of 200 mg) along with a 14-week prednisone taper, and the other receiving placebo along with a 52-week prednisone taper.

The primary outcome assessed at 52 weeks was sustained remission. This was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12, sustained normalisation of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52.

• A total of 118 patients participated in the study, with 60 in the sarilumab group and 58 in the placebo group.
  
• At week 52, the results demonstrated a significant difference in sustained remission between the two groups.
• Specifically, 28% of patients in the sarilumab group achieved sustained remission compared to only 10% in the placebo group.
• Furthermore, the sarilumab group had a significantly lower median cumulative glucocorticoid dose at 52 weeks (777 mg) compared to the placebo group (2044 mg).
• In terms of safety and adverse events, the most common adverse events observed in the sarilumab group compared to the placebo group were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhoea (12% vs. 2%).
• However, it's important to note that more treatment-related discontinuations were observed in the sarilumab group compared to the placebo group (12% vs. 7%).

These findings suggest that sarilumab may offer a promising treatment option for patients with polymyalgia rheumatica who experience relapse during glucocorticoid tapering. While the treatment showed efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose, further research and evaluation are needed to confirm these results and assess the treatment's long-term safety and effectiveness.

Reference:

Spiera, R. F., Unizony, S., Warrington, K. J., Sloane, J., Giannelou, A., Nivens, M. C., Akinlade, B., Wong, W., Bhore, R., Lin, Y., Buttgereit, F., Devauchelle-Pensec, V., Rubbert-Roth, A., Yancopoulos, G. D., Marrache, F., Patel, N., & Dasgupta, B. Sarilumab for relapse of polymyalgia rheumatica during glucocorticoid taper. The New England Journal of Medicine,2023;389(14):1263–1272. https://doi.org/10.1056/nejmoa2303452