International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus

Jean-François Kleinmann (1) , Florence Tubach (2) , Veronique Le Guern (3) , Alexis Mathian (4) , Christophe Richez (5) , David Saadoun (6) , Karim Sacré (7) , Jérémie Sellam (8) , Raphaèle Seror (9) , Zahir Amoura (10) , Emmanuel Andrès (11, 12) , Sylvain Audia (13) , Brigitte Bader-Meunier (14) , Gilles Blaison (15) , Bernard Bonnotte (13) , Patrice Cacoub (6) , Sophie Caillard (16) , Laurent Chiche (17) , Olivier Chosidow (18) , Nathalie Costedoat-Chalumeau (19) , Claire Daien (20) , Eric Daugas (7) , Nairouz Derdèche (12) , Andrea Doria (21) , Olivier Fain (22) , Fadi Fakhouri (23) , Dominique Farge (24) , Cem Gabay (25) , Sylvie Guillo (26) , Eric Hachulla (27) , Najia Hajjaj-Hassouni (28) , Mohamed Hamidou (29) , Frédéric Houssiau (30) , Noemie Jourde-Chiche (31, 32) , Isabelle Kone-Paut (33) , Aïcha Ladjouz-Rezig (34) , Olivier Lambotte (9) , Dan Lipsker (35) , Xavier Mariette (9) , Nicolas Martin-Silva (36) , Thierry Martin (37) , François Maurier (38) , Roderich Meckenstock (39) , Arsene Mekinian (40) , Olivier Meyer (41) , Shirine Mohamed (42, 43) , Jacques Morel (44) , Bruno Moulin (45) , Denis Mulleman (46) , Thomas Papo (47) , Vincent Poindron (48) , Xavier Puéchal (49) , Leonardo Punzi (21) , Pierre Quartier (50) , Laurent Sailler (51) , Amar Smail (52) , Martin Soubrier (53) , Agnès Sparsa (54) , Zoubida Tazi-Mezalek (55) , Leith Zakraoui (56) , Stéphane Zuily (43) , Jean Sibilia (57) , Jacques-Eric Gottenberg (58)

1 CHU Strasbourg
2 CIC epidémiologie clinique/ essais cliniques, Hôpital Bichat - Claude Bernard
3 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
4 Service de médecine interne [CHU Pitié-Salpétrière]
5 Hôpital Pellegrin
6 I3 - Immunologie - Immunopathologie - Immunothérapie
7 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
8 CHU Saint-Antoine [AP-HP]
9 Régulation de la réponse immune, infection VIH-1 et autoimmunité
10 Service d'Immunologie [CHU Pitié-Salpétrière]
11 CHRU Strasbourg
12 UNISTRA - Université de Strasbourg
13 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
14 Service Immunologie et Hématologie
15 CH Colmar - Hôpital Louis Pasteur [Colmar]
16 Service de néphrologie [Rennes]
17 Hôpital Européen [Fondation Ambroise Paré - Marseille]
18 Service de dermatologie [Mondor]
19 I3 - Immunologie - Immunopathologie - Immunothérapeutique
20 IGMM - Institut de Génétique Moléculaire de Montpellier
21 Unipd - Università degli Studi di Padova = University of Padua
22 service de médecine interne
23 Service de néphrologie adultes [CHU Necker]
24 UPD7 - Université Paris Diderot - Paris 7
25 Division of Rheumatology
26 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
27 Service de médecine interne [Lille]
28 Rheumatology and Physical Rehabilitaion Department
29 CHU Nantes - Centre hospitalier universitaire de Nantes
30 UCL - Université Catholique de Louvain = Catholic University of Louvain
31 AMU - Aix Marseille Université
32 VRCM - Vascular research center of Marseille
33 Service Pédiatrie
34 The University of Algiers
35 Biologie des Cellules Dendritiques Humaines
36 CHU Caen
37 Les Hôpitaux Universitaires de Strasbourg (HUS)
38 Service de médecine interne
39 CHV - Centre Hospitalier de Versailles André Mignot
40 Service de rhumatologie [CHU Saint-Antoine]
41 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
42 Service de Médecine Interne et Médecine Générale [CHRU Nancy]
43 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
44 Département de Rhumatologie[Montpellier]
45 Service de Néphrologie et Transplantation
46 GICC UMR 7292 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017]
47 Hôpital Bichat - Claude Bernard
48 ICT - Immunologie et chimie thérapeutiques
49 IC UM3 (UMR 8104 / U1016) - Institut Cochin
50 Service d'immuno-hématologie pédiatrique [CHU Necker]
51 CHU Toulouse [Toulouse]
52 Service de Néphrologie - Médecine Interne
53 CHU Clermont-Ferrand
54 Clinique Mutualiste Catalane
55 UM5 - Université Mohammed V de Rabat [Agdal]
56 University of Tunis El Manar
57 Service Physiologie
58 Immuno-Rhumatologie Moléculaire

Background/purpose: Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE. Methods: The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n=9), an evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations. Results: A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation. Conclusion: Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience.

Keywords: Biological; Recommendation; Lupus

Domains: Life Sciences [q-bio]; Human health and pathology; Rhumatology and musculoskeletal system; Life Sciences [q-bio]; Immunology; Immunotherapy; Life Sciences [q-bio]

Jean-François Kleinmann, Florence Tubach, Veronique Le Guern, Alexis Mathian, Christophe Richez, et al.. International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus. Autoimmunity Reviews, 2017, 16 (6), pp.650-657. ⟨10.1016/j.autrev.2017.04.011⟩. ⟨hal-01787368⟩