Response to mepolizumab according to disease manifestations in patients with eosinophilic granulomatosis with polyangiitis

Published:September 14, 2021DOI:https://doi.org/10.1016/j.ejim.2021.08.021

      Highlights

      • Mepolizumab elicited a heterogeneous response on different disease manifestations.
      • The number of flares was greatly reduced but not disappeared, being asthma and ENT flares the main types of exacerbations.
      • Mepolizumab allowed remarkable glucocorticoid tapering.
      • Despite glucocorticoid tapering, no vasculitic manifestations appeared under mepolizumab treatment

      Abstract

      Background

      Eosinophilic granulomatosis with polyangiitis (EGPA) is a relapsing disease with frequent glucocorticoid dependence. Mepolizumab has been demonstrated to reduce flares and spare glucocorticoids (GC). However, EGPA is a heterogeneous condition and the effects of mepolizumab on specific disease manifestations has not been completely delimitated.

      Objectives

      To analyse the impact of mepolizumab on manifestations derived from small-vessel vasculitis, ENT (ear, nose and throat) symptoms, asthma, eosinophilic tissue infiltration and anti-neutrophil cytoplasmic antibody (ANCA) status in a single-centre cohort of EGPA patients.

      Methods

      Medical charts of EGPA patients treated with mepolizumab were retrospectively reviewed by the authors to describe demographics, clinical characteristics, steroid dose at the initiation of mepolizumab and during follow-up, flares, disease activity, damage accrual and laboratory results.

      Results and conclusions

      Among 56 patients with EGPA regularly controlled at our department, 11 patients were treated with mepolizumab because of corticodependence and unsatisfactory disease control. The mean time of treatment was 38 months (range: 3-66 months). Patients with persistent symptoms improved their asthma control, but 3 of them persisted with recurrent ENT symptoms in spite of treatment with mepolizumab. None of the patients developed vasculitic manifestations (cutaneous, neurological, gastrointestinal, renal) during treatment. All patients achieved a Birmingham Vasculitis Activity Score (BVAS) of 0 points at 12 months or earlier. In general, patients reduced the number of flares, which tended to be milder, and all related to asthma or ENT manifestations. The improvement in disease activity allowed notable glucocorticoid tapering.

      Keywords

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      References

        • Jennette JC
        • Falk RJ
        • Bacon PA
        • et al.
        Revised international chapel Hill consensus conference nomenclature of vasculitides.
        Arthritis Rheum. 2012; 65 (2013): 1-11https://doi.org/10.1002/art.37715
        • Moosig F
        • Bremer JP
        • Hellmich B
        • et al.
        A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients.
        Ann Rheum Dis. 2013; 72: 1011-1017https://doi.org/10.1136/annrheumdis-2012-201531
        • Comarmond C
        • Pagnoux C
        • Khellaf M
        • et al.
        Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort.
        Arthritis Rheum. 2013; 65: 270-281https://doi.org/10.1002/art.37721
        • Trivioli G
        • Terrier B
        • Vaglio A.
        Eosinophilic granulomatosis with polyangiitis: understanding the disease and its management.
        Rheumatol (UK). 2020; 59: iii84-iii94https://doi.org/10.1093/rheumatology/kez570
        • Padoan R
        • Marconato M
        • Felicetti M
        • et al.
        Overall disability sum score for clinical assessment of neurological involvement in eosinophilic granulomatosis with polyangiitis.
        J Clin Rheumatol. 2018; 24: 197-202https://doi.org/10.1097/RHU.0000000000000713
        • Cottin V
        • Bel E
        • Bottero P
        • et al.
        Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
        Eur Respir J. 2016; 48: 1429-1441https://doi.org/10.1183/13993003.00097-2016
        • Durel CA
        • Berthiller J
        • Caboni S
        • et al.
        Long-term followup of a multicenter cohort of 101 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
        Arthritis Care Res. 2016; 68: 374-387https://doi.org/10.1002/acr.22686
        • Wechsler ME
        • Akuthota P
        • Jayne D
        • et al.
        Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis.
        N Engl J Med. 2017; 376: 1921-1932https://doi.org/10.1056/NEJMoa1702079
        • Masi AT
        • Hunder GG
        • Lie JT
        • et al.
        The American College of Rheumatology 1990 criteria for the classification of churg-strauss syndrome (allergic granulomatosis and angiitis).
        Arthritis Rheum. 1990; 33: 1094-1100https://doi.org/10.1002/art.1780330806
        • Mukhtyar C
        • Lee R
        • Brown D
        • et al.
        Modification and validation of the Birmingham vasculitis activity score (version 3).
        Ann Rheum Dis. 2009; 68: 1827-1832https://doi.org/10.1136/ard.2008.101279
        • Exley AR
        • Bacon PA
        • Luqmani RA
        • et al.
        Development and initial validation of the vasculitis damage index for the standardized clinical assessment of damage in the systemic vasculitides.
        Arthritis Rheum. 1997; 40: 371-380https://doi.org/10.1002/art.1780400222
        • Guillevin L
        • Pagnoux C
        • Seror R
        • et al.
        The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the french vasculitis study group (FVSG) cohort.
        Medicine (Baltimore). 2011; 90: 19-27https://doi.org/10.1097/MD.0b013e318205a4c6
        • Moosig F
        • Gross WL
        • Herrmann K
        • et al.
        Targeting Interleukin-5 in refractory and relapsing churg–strauss syndrome.
        Ann Intern Med. 2011; 155: 341https://doi.org/10.7326/0003-4819-155-5-201109060-00026
        • Herrmann K
        • Gross WL
        • Moosig F.
        Extended follow-up after stopping mepolizumab in relapsing/refractory Churg-Strauss syndrome.
        Clin Exp Rheumatol. 2012; 30
        • Kim S
        • Marigowda G
        • Oren E
        • et al.
        Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome.
        J Allergy Clin Immunol. 2010; 125: 1336-1343https://doi.org/10.1016/j.jaci.2010.03.028
        • Steinfeld J
        • Bradford ES
        • Brown J
        • et al.
        Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis.
        J Allergy Clin Immunol. 2019; 143: 2170-2177https://doi.org/10.1016/j.jaci.2018.11.041
        • Pouliquen IJ
        • Austin D
        • Steinfeld J
        • et al.
        Justification of the subcutaneous mepolizumab dose of 300 mg in eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.
        Clin Ther. 2021; xxx: 4-6https://doi.org/10.1016/j.clinthera.2021.05.014