Benefits of Mepolizumab for EGPA Treatment Similar Among Patients With or Without Vasculitic Phenotypes

Mepolizumab may provide similar clinical benefits among patients with eosinophilic granulomatosis with polyangiitis (EGPA) with or without a vasculitic phenotype, according to results of a post hoc analysis published in ACR Open Rheumatology.

Though considered standard, treatment of EGPA with systemic glucocorticoids, immunosuppressants, and biologics is associated with toxicity and relapse. Investigators aimed to assess the efficacy of mepolizumab for treatment of EGPA among patients with or without a vasculitic phenotype.

A post hoc analysis of the randomized, phase 3, MIRRA trial (ClinicalTrials.gov Identifier: NCT02020889) was conducted. The parent study included 136 adult patients with relapsing/refractory EGPA who received at least 4 weeks of stable oral glucocorticoids. In addition to standard of care, half of these patients (n=68) received mepolizumab 300 mg subcutaneous every 4 weeks for 52 weeks and half received placebo (n=68).

Atineutrophil cytoplasmic antibody (ANCA) history, baseline Birmingham Vasculitis Activity Score (BVAS), and Vasculitis Damage Index (VDI) scores were used to evaluate EGPA vasculitic phenotype. Remission was defined as a BVAS equal to 0 and an oral glucocorticoids dose of at least 4 mg/day of a prednisone equivalent.

Accrued remission over 52 weeks and number of patients in remission at weeks 36 and 48 were the primary outcomes. Secondary outcomes included evaluation of EGPA vasculitic characteristics and types of relapses.

Investigators found that regardless of baseline VDI, baseline BVAS, or history of ANCA positivity status, mepolizumab was associated with a greater number of patients in remission at weeks 36 and 48 and greater accrued remission duration compared with placebo.

Remission was achieved with mepolizumab vs placebo at weeks 36 and 48 among patients with VDI scores less than 5 (29% vs 6%) and among those with VDI scores of at least 5 (37% vs 0%), among patients with BVAS of 0 (45% vs 5%) and among those with BVAS greater than 0 (22% vs 2%), and among patients with (54% vs 0%) and without  (27% vs 4%) history of ANCA positivity, respectively.

Over the 52-week treatment period, 36 patients in the mepolizumab group and 13 patients in the placebo group achieved remission. Additionally, 9 patients in the mepolizumab group and 2 in the placebo group achieved accrued remission for at least 36 weeks.

Investigators noted similar baseline vasculitic characteristics among patients achieving vs not achieving remission.

Treatment with mepolizumab was associated with a reduction in all types of relapses compared with placebo (56% vs 82%). Fewer patients in the mepolizumab group experienced EGPA relapses, as well as achieving a lower number of overall relapse events (88 events vs 154 events).

Results were similar among patients who did or did not accrue at least 36 weeks of remission. However, a greater number of patients who accrued at least 36 weeks of remission had a presence or history of neuropathy vs those who didn’t (64% vs 39%, respectively).

A lack of biopsy criteria to support identification of a vasculitic phenotype and small sample sizes may limit study results. Additionally, though the presence of neuropathy commonly suggests vasculitis, its cause among patients in this study was unknown.  

Investigators concluded, “These results suggest patients with EGPA and a vasculitic phenotype are likely to achieve clinical benefits with mepolizumab, thus providing valuable information for clinicians treating patients with EGPA with and without vasculitic phenotypes.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.