Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study

Bettiol, Alessandra; Urban, Maria Letizia; Bello, Federica; Fiori, Davide; Mattioli, Irene; Lopalco, Giuseppe; Iannone, Florenzo; Egan, Allyson; Dagna, Lorenzo; Caminati, Marco; Negrini, Simone; Bargagli, Elena; Folci, Marco; Franceschini, Franco; Padoan, Roberto; Floßmann, Oliver; Solans, Roser; Schroeder, Jan Walter; André, M.; Moi, Laura; Parronchi, Paola; Roccatello, Dario; Sciascia, Savino; Jayne, David; Prisco, Domenico; Vaglio, Augusto; Emmi, Giacomo

doi:10.1136/ard-2022-222776

Cited by 22 publications

(26 citation statements)

References 7 publications

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“… 40 Regarding EGPA, even if it is also classified as an AAV, 1 this vasculitis has notable differences and it is not treated exactly the same as GPA and MPA, including an approach that increasingly targets eosinophils. 41 42 …”

Section: Discussionmentioning

confidence: 99%

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis

et al. 2023

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ObjectiveTo develop a score assessing the probability of relapse in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).MethodsLong-term follow-up data from GPA and MPA patients included in five consecutive randomised controlled trials were pooled. Patient characteristics at diagnosis were entered into a competing-risks model, with relapse as the event of interest and death the competing event. Univariate and multivariate analyses were computed to identify variables associated with relapse and build a score, which was then validated in an independent cohort of GPA or MPA patients.ResultsData collected from 427 patients (203 GPA, 224 MPA) at diagnosis were included. Mean±SD follow-up was 80.6±51.3 months; 207 (48.5%) patients experienced ≥1 relapse. Relapse risk was associated with proteinase 3 (PR3) positivity (HR=1.81 (95% CI 1.28 to 2.57); p<0.001), age ≤75 years (HR=1.89 (95% CI 1.15 to 3.13); p=0.012) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (HR=1.67 (95% CI 1.18 to 2.33); p=0.004) at diagnosis. A score, the French Vasculitis Study Group Relapse Score (FRS), from 0 to 3 points was modelised: 1 point each for PR3-antineutrophil cytoplasmic antibody positivity, eGFR ≥30 mL/min/1.73 m² and age ≤75 years. In the validation cohort of 209 patients, the 5-year relapse risk was 8% for a FRS of 0, 30% for 1, 48% for 2 and 76% for 3.ConclusionThe FRS can be used at diagnosis to assess the relapse risk in patients with GPA or MPA. Its value for tailoring the duration of maintenance therapy should be evaluated in future prospective trials.

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Section: Discussionmentioning

confidence: 99%

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis

et al. 2023

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“…Timing of biologic treatment start in respect of the acute disease onset is also crucial for selecting the right dose and the association with other immunosuppressant strategies. The real-life study recently published by the European Study Group supported the safety and relevance of sequential rituximab and MEP 100 mg therapy in inducing and maintaining remission of both systemic and respiratory EGPA manifestations [76]. When the remission induction is the clinical need, both the autoimmune and eosinophilic-driven underlying mechanisms should be taken into consideration as treatment targets.…”

Section: Future Targetsmentioning

confidence: 99%

The new indications for biologicals in type 2 diseases: perspectives

Bagnasco

Canevari

Passalacqua

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewTo provide a literature review of what is on the market and under study for some diseases treated with drugs targeting type 2 (T2) inflammation.Recent findingsLiterature data have shown that drugs targeting type 2 inflammation are effective in asthma and nasal polyposis, conditions for which they are on the market, and have promising expectations in the case of eosinophilic esophagitis, especially using anti-IL-5/IL-5 receptor and IL-4 receptor antibodies, while concerning eosinophilic granulomatosis with polyangitis (EGPA), mepolizumab (MEP) was approved by FDA and EMA as a drug for the treatment of this condition because of the promising results obtained in trials and in real life.SummaryThe use of these drugs is certainly an important achievement in the treatment of complex diseases such as those mentioned above, which are too often orphaned from innovative treatments and limited to the use of immunosuppressants and systemic corticosteroid for their control.

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“…More recently, a multicenter, European retrospective, observational study including 38 patients with EGPA who received induction therapy with RTX followed within 1 year by mepolizumab (either 100 mg or 300 mg/month), showed that a sequential therapeutic regimen may be effective and safe for remission induction and maintenance of both systemic and respiratory EGPA manifestations [38].…”

Section: The Real-world Evidencementioning

confidence: 99%

“…Taken together those data suggest that addressing an EGPA patient to an anti T2 biologic drug should follow a tailored approach, driven by a careful evaluation including disease stage and patient's clinical features. As an example, the above mentioned real-life study recently published by the European Study Group reported on the successful use of sequential rituximab and mepolizumab 100 mg therapy in inducing and maintaining remission of both systemic and respiratory EGPA manifestations [38]. On the other side, in patients previously experiencing EGPA and, once induced the systemic remission, still suffering from severe steroid-dependent eosinophilic asthma, mepolizumab alone at the dose of 100 mg/4 weeks has shown to prevent disease relapses, with a consistent steroid an immunosuppressive -sparing effect [41].…”

Section: Conclusion -Controversial Aspect and Future Directionsmentioning

confidence: 99%

Biologics for eosinophilic granulomatosis with polyangiitis

Caminati

Maule

Bello

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewThe link between severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA) in terms of pathophysiological background, clinical manifestations and disease evolution has leaded to investigate the relevance of anti T2 monoclonal antibodies licensed for severe asthma patients as a treatment option for EGPA. The present review aimed to provide un update on EGPA pathophysiology and to critically summarize the most robust evidence coming from trials and real-life setting on the use of anti T2 biologics in EGPA patients.Recent findingsMepolizumab, an anti-interleukin-5 monoclonal antibody, is the only biologic drug targeting eosinophilic inflammation currently approved for EGPA treatment at the dose of 300 mg/4 weeks. Its use is restricted by the American College of Rheumatology guidelines to specific diseases phases and severity grades. However the most appropriate mepolizumab positioning and dose is still under investigation in the real life practice, which is providing an increasing amount of evidence confirming its efficacy, alone or in combination with other options in different disease stages. The relevance of other monoclonal antibodies interfering with T2 inflammation, including omalizumab and benralizumab, is under investigation but the evidence is still scarceSummaryTaking into account the suboptimal medium-long term safety profile of conventional EGPA treatments, the opportunity of selectively targeting eosinophilic inflammation certainly represents a revolutionary approach. However, further real-word evidence is required to effectively position the new treatments in the light of the disease complexity, including different immunological drivers, and individual variability.

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Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study

Cited by 22 publications

References 7 publications

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis

The new indications for biologicals in type 2 diseases: perspectives

Biologics for eosinophilic granulomatosis with polyangiitis

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