Off-Label Use of Biotherapies to Treat Relapsing And/or Refractory Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss)

Alice Canzian ¹, Nils Venhoff ², Silvia Sartorelli ³, Anne-Marie Ruppert ⁴, Matthieu Groh ⁵, Camille Taille ⁶, Virginie Rieu ⁷, Perrine Smets ⁷, François Maurier ⁸, Nicolas Girszyn ⁹, Maxime Samson ¹⁰, Claire de Moreuil ¹¹, Grégory Pugnet ¹², Xavier Delbrel ¹³, Jean-Emmanuel Kahn ¹⁴, Xavier Puéchal for the French Vasculitis Study Group ¹⁵, Giacomo Emmi ¹⁶, Loic Guillevin ¹⁵, Lorenzo Dagna ¹⁷, Jens Thiel ², Augusto Vaglio ¹⁸ and Benjamin Terrier¹⁵, ¹Cochin Hospital, Paris, France, ²Clinic for Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany, ³Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy, ⁴Tenon Hospital, Paris, France, ⁵Service de Médecine Interne, Centre de Référence des Syndromes Hyperéosinophiliques-CEREO, Hôpital Foch, Université Versailles–Saint-Quentin-en-Yvelines, Suresnes, France, Suresnes, France, ⁶Bichat Hospital, Paris, France, ⁷CHU, Clermont-Ferrand, France, ⁸Service de Médecine Interne, Hôpital Belle Isle, Metz, Metz, France, ⁹CHU, Rouen, France, ¹⁰Service de Médecine Interne et Immunologie Clinique, CHU Dijon Bourgogne, Hôpital François Mitterrand, Dijon ; Université Bourgogne-Franche Comté, INSERM, EFS BFC, UMR1098, F-21000 Dijon, Dijon, France, ¹¹CHU Brest, Brest, France, ¹²CHU de Toulouse, Hôpital Purpan, Service de Médecine Interne, Toulouse, France, ¹³CH, Pau, France, ¹⁴APHP, Boulogne Billancourt, France, ¹⁵National Referral Center for Rare Systemic Autoimmune Diseases Paris Cochin, Paris, France, ¹⁶Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy, Florence, Italy, ¹⁷Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy, ¹⁸Nephrology Unit, Parma University Hospital, Parma, Italy, Nephrology Unit, Parma University Hospital, Parma, Italy, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Churg-Strauss syndrome, systemic vasculitides and Biologic agents

Session Information

Date: Sunday, November 10, 2019

Session Title: 3S085: Vasculitis – ANCA-Associated I (869–874)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg–Strauss syndrome), is characterized by small-vessel necrotizing vasculitis, and blood and tissue eosinophilia in asthmatic individuals. Glucocorticoids (GCs) usually control EGPA, but vasculitis relapses and GC-dependent asthma are frequent, as are long-term adverse events, leading to potential biotherapy use. We examined off-label biological therapy use for relapsing/refractory EGPA.

Methods:

This retrospective European collaborative study included patients with EGPA, meeting the ACR criteria and/or Chapel Hill Consensus Conference definitions. Treatment efficacy and safety were recorded. Remission was defined as the absence of asthma, sinonasal and vasculitis manifestations with ≤5 mg/day of prednisone, and partial response as the absence of manifestations but requiring 6–10 mg/day of prednisone.

Results:

Among the147 patients (74 men, 73 women; median age 52 years) included, 63 (43%) received rituximab (RTX), 51 (35%) mepolizumab (MEPO), at monthly respective doses of 100 mg or 300 mg for 29 (57%) and 22 (43%), and 33 (22%) omalizumab (OMA). Previous treatments were: GCs for all, azathioprine (68%), cyclophosphamide (40%), methotrexate (29%) or mycophenolate mofetil (15%).

At inclusion, median (interquartile range) BVAS in the RTX, OMA and MEPO groups, respectively, were 8.5 (5-13), 2 (2-5) and 2 (2-6). In the RTX-treated patients, median BVAS fell to 1 (0-4.5) at 6 and 0 (0-2) ay 12 months.A Median GCs dose decreased to 7.5 (5-10) at 6 months and 12 months. Overall, remissions, partial responses, therapeutic failure and stop for adverse event, respectively, were noted in 49%, 24%, 24% and 3% for RTX recipients. Remission was observed in 57% of ANCA-positive patients compared to 42% in ANCA-negative patients.

To treat GC-dependent asthma, MEPO had a much better GCs-sparing effect than OMA, and a better overall response. Remissions, partial responses, therapeutic failure and stop for adverse event, respectively, were noted in 15%, 33%, 48% and 4% for OMA recipients and 78%, 10%, 8% and 4% for MEPO recipients.Finally, no obvious difference was noted between patients receiving MEPO 100 mg and those 300 mg monthly, in terms of GC-sparing effect and overall response.

Sixteen (25%) patients stopped RTX: 2 for adverse events, and 14 for refractory disease. Also, 17 (27%) experienced adverse events, mainly severe infections. Seventeen (52%) stopped OMA: 1 for severe infusion reaction, and 16 for refractory disease. Four (12%) patients receiving OMA experienced mild to moderate adverse events. Three (6%) patients stopped MEPO: 2 for adverse events (one severe infusion reaction and one because of paraesthesia), and 1 for pregnancy. Eleven (22%) patients receiving MEPO experienced mild to moderate adverse events, mainly asthenia.

Conclusion: These results suggest that RTX could be effective for 50% of patients with EGPA vasculitis relapses, with an acceptable safety profile. MEPO is highly effective with a good GCs-sparing effect and safety profile in patients with GCs-dependant asthma, and 100 mg monthly seems to be an acceptable dose at first-line.

Disclosure: A. Canzian, None; N. Venhoff, Novartis, 2, 5; S. Sartorelli, None; A. Ruppert, None; M. Groh, None; C. Taille, None; V. Rieu, None; P. Smets, None; F. Maurier, None; N. Girszyn, None; M. Samson, None; C. de Moreuil, None; G. Pugnet, None; X. Delbrel, None; J. Kahn, None; X. Puéchal for the French Vasculitis Study Group, LFB, 8, Pfizer, 2, 8, Roche, 8; G. Emmi, None; L. Guillevin, None; L. Dagna, AbbVie, 5, Amgen, 5, Biogen, 5, Bristol-Myers Squibb, 5, Celltrion, 5, Novartis, Pfizer, 5, Sanofi-Genzyme, 5, SOBI, 2, 5; J. Thiel, Novartis Pharma GmbH, 2, 5; A. Vaglio, None; B. Terrier, Grifols, 8, GSK, 8, LFB, 8, Roche, 8.

To cite this abstract in AMA style:

Canzian A, Venhoff N, Sartorelli S, Ruppert A, Groh M, Taille C, Rieu V, Smets P, Maurier F, Girszyn N, Samson M, de Moreuil C, Pugnet G, Delbrel X, Kahn J, Puéchal for the French Vasculitis Study Group X, Emmi G, Guillevin L, Dagna L, Thiel J, Vaglio A, Terrier B. Off-Label Use of Biotherapies to Treat Relapsing And/or Refractory Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/off-label-use-of-biotherapies-to-treat-relapsing-and-or-refractory-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss/. Accessed January 23, 2022.

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