Immune deficiencies, infection, and systemic immune disorders
Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome

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Background

Treatments for Churg-Strauss syndrome (CSS), a rare eosinophilic vasculitis characterized by asthma, sinusitis, peripheral eosinophilia, pulmonary infiltrates, and tissue infiltration, are limited by toxicity or poor efficacy. Levels of IL-5, a cytokine regulating eosinophils, can be increased in patients with CSS. Mepolizumab, a humanized monoclonal anti–IL-5 antibody, decreases steroid requirements in patients with non-CSS hypereosinophilic syndromes.

Objective

The purpose of this study was to assess whether mepolizumab would safely allow corticosteroid tapering in patients with steroid-dependent CSS while decreasing serum markers of disease activity.

Methods

This open-label pilot study treated 7 patients with 4 monthly doses of mepolizumab to assess whether it safely decreased CSS disease activity and permitted tapering of systemic corticosteroids.

Results

Mepolizumab was safe and well tolerated in patients with CSS. Mepolizumab reduced eosinophil counts and allowed for safe corticosteroid reduction in all 7 subjects. On cessation of mepolizumab, CSS manifestations recurred, necessitating corticosteroid bursts.

Conclusion

Mepolizumab is a safe and well-tolerated therapy in patients with CSS, offering clinical benefit by enabling corticosteroid tapering while maintaining clinical stability.

Section snippets

Methods

This open-label pilot study was approved by the Brigham and Women's Hospital Institutional Review Board. Patients were recruited nationally through the clinicaltrials.gov Web site and the investigators' clinical practices.

Results

Five female and 2 male patients enrolled and completed the study (mean age, 45 years; range, 28-62 years). All met American College of Rheumatology clinical criteria, and all had historical eosinophil counts of greater than 10%. All of the patients identified themselves as white. Two were undergoing methotrexate therapy, and one was receiving both methotrexate and hydroxychloroquine before enrollment. These 3 patients remained on stable doses of these therapies throughout the study. At

Discussion

CSS remains a challenge for clinicians because the current standard-of-care therapies, corticosteroids and immunomodulators, do not always control symptoms and are often associated with significant morbidity. New therapies are urgently needed. However, because this is a rare orphan disease, testing novel therapies is challenging because few centers have sufficient numbers of patients to undertake randomized placebo-controlled trials.

Based on this pilot trial, it appears that adjuvant therapy

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  • Cited by (0)

    Supported by an investigator-initiated grant from GlaxoSmithKline. This study is registered at Clinicaltrials.gov as GRANT00375947.

    Disclosure of potential conflict of interest: E. Oren is on the speaker's bureau for Meda Pharmaceuticals and GlaxoSmithKline. E. Israel has consultant arrangements with Abbott, Amgen, Astellas Pharma US, Cowen & Co, GlaxoSmithKline, Icagen, MedImmune, Merck, NewMentor, NKT Therapeutics, Novartis, PDL Biopharma, Pulmatrix, Schering-Plough, Sepracor, and Teva Specialty Pharmaceuticals and receives research support from Aerovance, Ception Therapeutics, Genentech, Icagen, Johnson & Johnson, MedImmune, the National Institutes of Health, and Novartis. M. E. Wechsler is a consultant for GlaxoSmithKline and MedImmune and receives research support from GlaxoSmithKline and Ception Therapeutics. The rest of the authors have declared that they have no conflict of interest.

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