Reply to "mepolizumab in Patients with Eosinophilic Granulomatosis with Polyangiitis in Remission: What is the Right Dose?"
The journal of allergy and clinical immunology In practice(2021)
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We are grateful to Akdime and coauthors1Akdime F. Puéchal X. Rochea N. Mepolizumab in patients with EGPA in remission: what is the right dose?.J Allergy Clin Immunol Pract. 2021; 9: 2942-2943Abstract Full Text Full Text PDF Scopus (1) Google Scholar for their valuable contribution to the debate on the place and relevance of anti-IL5 biologic treatments in eosinophilic granulomatosis with polyangiitis (EGPA), which currently represents a challenging hot topic. By confirming our data,2Caminati M. Crisafulli E. Lunardi C. Micheletto C. Festi G. Maule M. et al.Mepolizumab 100 mg in severe asthmatic patients with EGPA in remission phase.J Allergy Clin Immunol Pract. 2021; 9: 1386-1388Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar the study by Akdime and coauthors on mepolizumab 100 mg/4 wk in severely asthmatic patients with EGPA in the remission phase supports the concept that precisely defining a target population for a specific treatment and dose is essential when managing biologic drugs, especially in the context of EGPA. In fact, its pathogenesis is complex enough to offer different potential therapeutic targets, and identifying the most appropriate one is crucial to achieve disease control and attain the maximal steroid or immunosuppressive sparing effect of the selected treatment option. As we pointed out in a recently published commentary3Caminati M. Giollo A. Senna G. Lunardi C. Biologics for eosinophilic granulomatosis with polyangiitis: one size does not fit all.https://doi.org/10.1002/art.41695Google Scholar on the real-life report about biologic drugs in EGPA by the European EGPA study group,4Canzian A. Venhoff N. Urban M.L. Sartorelli S. Ruppert A.M. Groh M. et al.Use of biologics to treat relapsing and/or refractory eosinophilic granulomatosis with polyangiitis: data from a European collaborative study.Arthritis Rheumatol. 2021; 73: 498-503Crossref PubMed Scopus (18) Google Scholar in addition to demonstrating the general efficacy of biologics, validating a phenotype-tailored approach should be the goal. Indeed, the heterogeneity of the study population in terms of the type and entity of organ involvement when initiating mepolizumab treatment may be a potential explanation for the considerable proportion of patients who failed to reach the protocol-defined outcomes in the Mepolizumab In Relapsing or Refractory EGPA (MIRRA) trial.5Wechsler M.E. Akuthota P. Jayne D. Khoury P. Klion A. Langford C.A. et al.Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis.N Engl J Med. 2017; 376: 1921-1932Crossref PubMed Scopus (384) Google Scholar Although it is currently supported by limited evidence, the use of mepolizumab 100 mg/4 wk in patients with persisting severe asthma and EGPA in the remission phase relies on a strong rationale. From the pathophysiologic perspective, an EGPA march concept could be hypothesized. In fact, in patients experiencing severe asthma and EGPA, the two conditions can be considered different clinical expressions of the same underlying eosinophilic inflammation, in which EGPA represents the peak of its systemic manifestation and severe asthma is both a prodromal condition and a postvasculitis clinical stage.6Cottin V. Bel E. Bottero P. Dalhoff K. Humbert M. Lazor R. et al.Groupe d’Etudes et de Recherche sur les Maladies Orphelines Pulmonaires (GERM“O”P)Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): a study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss).Autoimmun Rev. 2017; 16: 1-9PubMed Google Scholar This background, together with strong evidence of the beneficial effects of mepolizumab 100 mg/4 wk in severe asthma,7Pavord I. Menzies-Gow A. Buhl R. Chanez P. Dransfield M. Lugogo N. et al.Clinical development of mepolizumab for the treatment of severe eosinophilic asthma: on the path to personalized medicine.J Allergy Clin Immunol Pract. 2021; 9: 1121-1132.e7Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar supports its use in a well-defined EGPA population, as described earlier. In the study by Akdime and coauthors,1Akdime F. Puéchal X. Rochea N. Mepolizumab in patients with EGPA in remission: what is the right dose?.J Allergy Clin Immunol Pract. 2021; 9: 2942-2943Abstract Full Text Full Text PDF Scopus (1) Google Scholar despite a documented steroid-sparing effect in the whole sample, only one patient withdrew from steroid treatment. In contrast, we reported that nine of 16 patients completely discontinued oral steroids (56.2%).2Caminati M. Crisafulli E. Lunardi C. Micheletto C. Festi G. Maule M. et al.Mepolizumab 100 mg in severe asthmatic patients with EGPA in remission phase.J Allergy Clin Immunol Pract. 2021; 9: 1386-1388Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar In our population, nine of 11 patients maintained the immunosuppressive drug 6 months after mepolizumab initiation, although four reduced the dose, and two completely stopped that treatment. Currently available recommendations do not indicate whether steroid rather than immunosuppressive agents should be withdrawn first in the maintenance phase. Because of the well-known effects of systemic steroid therapy on bones and metabolism, we decided to stop it first. However, a number of open issues should be specifically addressed by further investigations, including the dose-response effect of biologics, their ability to prevent EGPA onset in severe asthmatic patients undergoing that treatment, and the management of nonresponders. In this regard, we should not forget that eosinophilic inflammation targeted by anti-IL5 drugs represents only one mechanism underlying the complex picture of EGPA pathophysiology. Mepolizumab in patients with eosinophilic granulomatosis with polyangiitis in remission: What is the right dose?The Journal of Allergy and Clinical Immunology: In PracticeVol. 9Issue 7PreviewAfter the pivotal randomized controlled trial in which patients with eosinophilic granulomatosis with polyangiitis (EGPA) received 300 mg mepolizumab every 4 weeks, the US Food and Drug Administration expanded the approved use of mepolizumab to treat patients with EGPA. Conversely, in Europe, mepolizumab is not yet licensed for EGPA patients with severe asthma, and clinicians can use only the 100 mg/4 wk regimen that has already been approved in these patients. Therefore, we read with great interest the Clinical Communication by Caminati et al1 on the follow-up of 16 severely asthmatic patients with EGPA in remission, in whom mepolizumab 100 mg was administered monthly. Full-Text PDF
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