Anti-IL-5 Drugs Cut Steroid Use in EGPA: Michael Wechsler, MD, MMSc

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Prior studies evaluating the efficacy of biologics targeting interleukin-5 (IL-5) or its receptor on eosinophils were a major breakthrough for treating patients with eosinophilic granulomatosis with polyangiitis (EGPA).

The MIRRA (NCT02020889) and MANDARA (NCT04157348) phase 3 clinical trials demonstrated the clinical efficacy of these monoclonal antibodies in inducing remission and reducing oral steroid use.^1,2 Historically, EGPA was managed with high doses of corticosteroids and/or immunosuppressants, which were associated with significant adverse effects, toxicity, and a lack of efficacy, Michael Wechsler, MD, MMSc, a pulmonologist at National Jewish Health, said in an interview with The American Journal of Managed Care^®. But anti-IL-5 therapies have been a significant addition to the EGPA treatment armamentarium.

“It's resulted in a significant reduction in oral steroid use,” he said. “We've had many patients who've been able to cut their steroid dose in half or more. We've had many patients who've been able to come off of oral corticosteroids and avoid all of their significant side effects.”

In the MIRRA trial, which included 136 patients, those randomized to mepolizumab, an anti-IL-5 monoclonal antibody, experienced significantly more accrued weeks of remission compared with placebo (28% vs 3% of participants had ≥24 weeks of accrued remission; OR, 5.91; 95% CI, 2.68-13.03; P < .001).¹

More patients in the mepolizumab group were also in remission at both week 36 and week 48 compared with placebo (32% vs 3%; OR, 16.74; 95% CI, 3.61-77.56; P < .001).¹

The MANDARA trial compared the efficacy of mepolizumab and benralizumab, a monoclonal antibody against the IL-5 receptor α subunit. Of the 140 patients randomized 1:1 to receive mepolizumab or benralizumab, 58% of those receiving benralizumab and 56% of those receiving mepolizumab were in remission at weeks 36 and 48, showing benralizumab was noninferior but not superior to mepolizumab (difference, 1 percentage point; 95% CI, –14 to 17; P = .88 for superiority).²

Directly targeting eosinophils with an anti-IL-5 therapy can help patients avoid side effects commonly associated with corticosteroids and immunosuppressive therapies, Wechsler emphasized.

Longer-acting anti-IL-5 therapies, such as depemokimab, which is administered twice a year, could also reduce the treatment burden for patients, which Wechsler said is exciting for EGPA.

“It's a good time to have EGPA because we have these therapies,” he concluded.

References

1. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921-1932. doi:10.1056/NEJMoa1702079

2. Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2024;390(10):911-921. doi:10.1056/NEJMoa2311155