Benralizumab facilitates complete withdrawal of OGCs more than mepolizumab in EGPA

Benralizumab offers more sustained and earlier elimination of oral glucocorticoids (OGCs) compared with mepolizumab in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA), suggests a post hoc analysis of the phase III MANDARA study presented at EULAR 2024.

Over twofold more patients treated with benralizumab vs mepolizumab achieved 100-percent reduction in OGC dose by week 40 and maintained this reduction through week 52 (24.3 percent vs 10 percent; hazard ratio [HR], 2.97, 95 percent confidence interval [CI], 1.26–7.77; p=0.0268). [EULAR 2024, abstract OP0188]

While patients tended to completely withdraw OGCs towards the end of the study, the median accrued duration of being off OGCs during the 52-week period was 1.9 weeks for patients treated with benralizumab vs 0 weeks for those treated with mepolizumab.

Head-to-head rare autoimmune disease trial

EGPA is the rarest type of anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis, characterized by eosinophilic tissue infiltration of the lungs, skin, heart, gastrointestinal tract, and nerves. OGCs are the recommended first-line treatment for this immune-mediated inflammatory disease. [Nat Rev Rheumatol 2023;19:378-393]

In MANDARA, benralizumab, an anti-IL-5 receptor α biologic, was demonstrated to be noninferior to mepolizumab, an anti-IL-5 biologic, with respect to the primary endpoint of remission. The risk of relapse was also similar between the two eosinophil-depleting therapies.

One notable difference reported in the primary analysis was that significantly more patients treated with benralizumab achieved complete withdrawal of OGCs during weeks 48 through 52 vs those treated with mepolizumab (41.4 percent vs 25.8 percent; adjusted difference, 15.7 percentage points; nominal p=0.0406). [ACR 2023, poster L14; N Engl J Med 2024;390:911-921]

This difference was further examined in the current analysis. The higher complete OGC withdrawal rates with benralizumab remained consistent across disease characteristics, regardless of baseline use of immunosuppressive therapy, historical or baseline ANCA-positivity, and time from EGPA diagnosis (≤4 years or >4 years), except for baseline OGC dose at the cut-off of 12 mg/day. Here, the rate was nonsignificantly 2.9-percentage point higher with mepolizumab among patients taking ≥12 mg prednisolone or equivalent daily at baseline.

Complete OGC withdrawal vs OGC tapering

While the outcome of complete OGC withdrawal generally disfavoured mepolizumab, the rates of achieving ≥50-percent reduction in OGC dose by week 40 and maintaining it through week 52 were similar between arms (77.1 percent vs 70 percent with benralizumab vs mepolizumab, respectively; HR, 1.17, 95 percent CI, 0.79–1.74; p=0.3852).

Still, the success of OGC tapering favoured benralizumab. Both arms started at a baseline of 10 mg prednisolone or equivalent daily, with the median OGC dose decreasing to 1.2 mg/day between weeks 49 and 52 in the benralizumab arm vs 3 mg/day in the mepolizumab arm. The corresponding reductions were −88.2 percent and −77.2 percent, respectively, according to the current analysis.

Overall, randomization to benralizumab was associated with a reduction in OGC use, as reflected in the lower mean cumulative OGC dose vs mepolizumab over 52 weeks (1,919 vs 2,075 mg of prednisolone or equivalent).

“So, we are now really able to get down the OGC doses of these patients,” said lead author Professor Bernhard Hellmich from the Akademisches Lehrkrankenhaus der Universität Tübingen, Kirchheim unter Teck, Baden-Württemberg, Germany. “Because there is no clear correlation between the OGC dose and relapse rates, we can probably reduce the OGCs even faster now that we know the drug [benralizumab] works.”