medwireNews: Sequential treatment with rituximab followed by mepolizumab may be a promising strategy to treat the systemic and respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA), suggest findings from an observational study.
Discussing the rationale for combining these agents, Giacomo Emmi (University of Florence, Italy) and team say that rituximab is used to treat GPA and microscopic polyangiitis but “its efficacy on respiratory manifestations seems limited,” whereas the interleukin (IL)-5 inhibitor mepolizumab, recently approved for EGPA in Europe, “is effective [for] respiratory manifestations.”
The retrospective study included 38 people with EGPA who were treated with rituximab at various doses (most commonly 1 g every 2 weeks) followed by mepolizumab (100 mg every 4 weeks in most patients) after a median of 5 months.
As reported in a letter to the Annals of the Rheumatic Diseases, median Birmingham Vasculitis Activity Score improved significantly from 10 points at baseline to 2 points at a median of 26 months after starting mepolizumab (final follow-up), while the median eosinophil count decreased from 780 to 90 cells/µL.
The proportion of people experiencing an asthma attack in the previous month increased from 63.2% at baseline to 71.1% at the time of mepolizumab initiation, but decreased significantly, to 23.7%, at the final follow-up after mepolizumab treatment.
Emmi et al also note that “ANCA [anti-neutrophil cytoplasm antibody] negativisation occurred in a relevant proportion of patients” following the sequential therapy, with positivity rates of 70.6% at baseline, 31.3% at mepolizumab initiation, and 11.8% at final follow-up. The proportion of patients on glucocorticoids remained stable from baseline to mepolizumab initiation, at 97.4%, followed by a reduction to 81.6% by the end of the study.
Taken together, these findings confirm “the efficacy of rituximab for the control of systemic EGPA manifestations, while proving limited efficacy on respiratory symptoms,” and suggest that introducing mepolizumab allowed the reduction of asthma attacks, “while also contributing to the sustained remission of systemic features and glucocorticoid sparing,” say the researchers.
They add that “[t]he tolerability of the sequential rituximab-mepolizumab treatment was good.” Six patients experienced non-serious adverse events (AEs) while on rituximab treatment, while five had AEs on mepolizumab, including one serious case of COVID-19 pneumonia.
The team cautions that the study was limited by its retrospective nature and small patient numbers.
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