A prospective cohort study published in the The Korean Journal of Internal Medicine reports that low-dose mepolizumab (100 mg) may offer meaningful clinical benefit in patients with severe refractory eosinophilic granulomatosis with polyangiitis (EGPA), particularly in reducing systemic corticosteroid dependence and facilitating sustained remission in selected cases.
EGPA is a multisystem necrotizing vasculitis characterized by asthma, peripheral eosinophilia, and organ involvement, in which interleukin-5 (IL-5) plays a central pathogenic role. IL-5 drives eosinophil proliferation, maturation, activation, and survival. Elevated IL-5 levels are consistently observed in patients with active EGPA, supporting therapeutic targeting of the IL-5 axis. Biologic agents directed against this pathway, including mepolizumab, reslizumab, and benralizumab, are under active investigation, with mepolizumab currently the most extensively studied in EGPA. Mepolizumab is a humanized monoclonal antibody against IL-5 that neutralizes circulating IL-5, thereby inhibiting eosinophil maturation in the bone marrow and reducing circulating and tissue eosinophil counts.
The 2-year prospective observational cohort study enrolled patients with uncontrolled severe eosinophilic asthma and refractory EGPA who had been receiving systemic corticosteroids at a dose of at least 7.5 mg/day of prednisolone, with or without additional immunosuppressive therapy, for a minimum of six months. Participants were treated with mepolizumab 100 mg administered subcutaneously every four weeks for one year, followed by an additional year of observation after treatment cessation to evaluate durability of response. Serial blood samples were collected before, during, and after therapy to establish a longitudinal EGPA cohort and to assess immunologic and clinical parameters over time.
Three patients with EGPA completed all 16 study visits across the two-year study period. After one year of monthly mepolizumab at the 100 mg dose, all three patients were able to reduce their maintenance systemic corticosteroid dose. Two patients achieved complete discontinuation of systemic steroids and met criteria for EGPA remission during the treatment phase. Importantly, remission in these two patients was maintained throughout the subsequent one-year follow-up after discontinuation of mepolizumab, suggesting sustained disease control beyond active biologic therapy.
Although complete remission was not achieved in all participants, low-dose mepolizumab was associated with a clinically meaningful steroid-sparing effect in severe refractory EGPA. The persistence of remission after treatment withdrawal in responders raises the possibility that even the lower asthma-approved dose of 100 mg may induce durable immunologic modulation in selected patients.
These findings contribute to the evolving evidence base supporting IL-5–targeted therapy in EGPA and highlight the potential role of lower-dose regimens in carefully selected patients, particularly where long-term steroid toxicity remains a major concern. Larger controlled studies will be required to confirm durability, identify predictors of sustained remission, and define optimal dosing strategies in EGPA.
References
- Kim MA, Lee JH, Kim EK, Kim JH, Park J, Lee SH, Kim TB. Effectiveness of low-dose mepolizumab in refractory eosinophilic granulomatosis with polyangiitis: systemic steroid use and remission. Korean J Intern Med. 2026 Jan;41(1):163-174.
- Bettiol A, Urban ML, Dagna L, Cottin V, Franceschini F, Del Giacco S, et al. Mepolizumab for eosinophilic granulomatosis with polyangiitis: a European multicenter observational study. Arthritis Rheumatol. 2022;74(2):295–306.
- Faverio P, Bonaiti G, Bini F, Vaghi A, Pesci A. Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy. Ther Clin Risk Manag. 2018 Dec 7;14:2385-2396.