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. 2025 May 21;4(3):100498.
doi: 10.1016/j.jacig.2025.100498. eCollection 2025 Aug.

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

Hirsh D Komarow  1 , Jing Wang  2 , Robin Eisch  1 , Linda Scott  1 , Erica H Brittain  3 , Dean D Metcalfe  1
Affiliations

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

Hirsh D Komarow et al. J Allergy Clin Immunol Glob. .

Abstract

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.

Keywords: Mastocytosis; anti–IL-6; mast cells; sarilumab; tryptase.

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Conflict of interest statement

Supported by the 10.13039/100006492Division of Intramural Research, National Institute of Allergy and Infectious Diseases, 10.13039/100000002National Institutes of Health (NIH). This project was funded in whole or in part with federal funds from the 10.13039/100000054National Cancer Institute, NIH, under contract 75N91019D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services; nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Figures

Fig 1
Fig 1
CONSORT (Consolidated Standards of Reporting Trials) diagram.
Fig 2
Fig 2
MC-QoL score over time by treatment. Change of MC-QoL score at weeks 0, 4, 8, 12, and 16 by treatment arm (left, placebo; right, drug). Observed data are shown in solid circles; imputed data, empty circles.
See this image and copyright information in PMC

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