Treatment of indolent systemic mastocytosis with sarilumab is not supported in a randomized trial

Background: Indolent systemic mastocytosis is a clonal mast cell disease that results in an increase in mast cells in the skin, bone marrow, and other organ systems. IL-6 has been shown to promote mast cell maturation, proliferation, and reactivity in vitro. Serum levels of IL-6 correlate with sever...

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Main Authors: Hirsh D. Komarow, MD, Jing Wang, MS, Robin Eisch, RN, Linda Scott, CRNP, Erica H. Brittain, PhD, Dean D. Metcalfe, MD, MS
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Journal of Allergy and Clinical Immunology: Global
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772829325000992
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Summary:Background: Indolent systemic mastocytosis is a clonal mast cell disease that results in an increase in mast cells in the skin, bone marrow, and other organ systems. IL-6 has been shown to promote mast cell maturation, proliferation, and reactivity in vitro. Serum levels of IL-6 correlate with severity of disease and risk of progression of systemic disease. Objective: We conducted a double-blind placebo-controlled study to assess safety and efficacy for the use of sarilumab in improving the quality of life for those with indolent systemic mastocytosis. ClinicalTrial.gov registration NCT03770273. Methods: A double-blind trial randomized 16 participants. The primary analysis compared the arms on the Mastocytosis Quality of Life Questionnaire (MC-QoL) index at 16 weeks, adjusting for the baseline MC-QoL. Mean baseline MC-QoL was 47.8. Results: The difference between the arms in the primary analysis was not statistically significant, with the results favoring the placebo arm; mean absolute MC-QoL improvement in the placebo arm was 14.7 relative to 8.9 in the sarilumab arm. The estimated treatment effect from regression analysis was a 6.0-unit advantage of MC-QoL in the placebo arm (P = .40; 95% confidence interval, −8.9, 20.8), limiting a possible sarilumab advantage to at most 9 units of MC-QoL. Similar conclusions were observed for other quality-of-life indices. Conclusions: Results in this small trial did not support using sarilumab to treat this population and highlights the importance of double-blind randomized studies.
ISSN:2772-8293