Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial - Université de Tours Access content directly
Journal Articles European Respiratory Journal Year : 2023

Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial

1 CHU Trousseau [Tours]
2 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
3 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
4 Hôpital Nord [CHU - APHM]
5 AMU - Aix Marseille Université
6 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
7 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
8 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
9 Laboratoire d'Excellence INFLAMEX [Paris]
10 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
11 UP13 - Université Paris 13
12 Hôpital Avicenne [AP-HP]
13 CHU Tenon [AP-HP]
14 SU - Sorbonne Université
15 LBTO - Biologie Intégrative du Tissu Osseux
16 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
17 HUS - Les Hôpitaux Universitaires de Strasbourg
18 Nouvel Hôpital Civil de Strasbourg
19 HEGP - Hôpital Européen Georges Pompidou [APHP]
20 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
21 Irset - Institut de recherche en santé, environnement et travail
22 CHU Nice - Centre Hospitalier Universitaire de Nice
23 Centre hospitalier Saint-Joseph [Paris]
24 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
25 Service de pneumologie [Rennes] = Pneumology [Rennes]
26 CEPR - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100
27 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
28 Hôpital Louis Pradel [CHU - HCL]
29 UCBL - Université Claude Bernard Lyon 1
30 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
31 T2i - Transplantation, Immunologie, Inflammation [Tours]
Charles-Hugo Marquette
Hilario Nunes
  • Function : Author
Yurdagul Uzunhan

Abstract

Background Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first step therapies while rituximab is used as rescue therapy. Methods In a randomised, double blind, two-parallel group, placebo-controlled trial ( NCT02990286 ), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune feature) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinico-biological data and a NSIP-like HRCT pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for six months. The primary endpoint was the change in percent of predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary endpoints included progression-free survival (PFS) up to 6 months and safety. Findings Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 ( se 1.13) in the rituximab+MMF group and −2.01 ( se 1.17) in the placebo+MMF group (between-group difference, 3.60 [95% CI 0.41 to 6.80]; p=0.0273). PFS was better in the rituximab+MMF group (crude HR 0.47 [95%CI 0.23 to 0.96]; p=0.03). Serious adverse events occurred in 26 patients of the rituximab+MMF group (41%) and in 23 of the placebo+MMF group (39%). Nine infections were reported in the rituximab+MMF group (five bacterial infections, 3 viral infections, 1 other) and four bacterial infections in the placebo+MMF group. Interpretation Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must consider the risk of viral infection.
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Origin Files produced by the author(s)

Dates and versions

hal-04113217 , version 1 (22-06-2023)
hal-04113217 , version 2 (26-09-2023)

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Julie Mankikian, Agnès Caille, Martine Reynaud-Gaubert, Marie-Sara Agier, Julien Bermudez, et al.. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial. European Respiratory Journal, 2023, 61 (6), pp.2202071. ⟨10.1183/13993003.02071-2022⟩. ⟨hal-04113217v2⟩
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