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Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study
  1. Guillaume Moulis1,2,3,
  2. Grégory Pugnet1,2,
  3. Nathalie Costedoat-Chalumeau4,5,
  4. Alexis Mathian6,
  5. Gaëlle Leroux7,8,
  6. Jonathan Boutémy9,
  7. Olivier Espitia10,
  8. Laurence Bouillet11,
  9. Sabine Berthier12,
  10. Jean-Baptiste Gaultier13,
  11. Pierre-Yves Jeandel14,
  12. Amadou Konaté15,
  13. Arsène Mékinian16,
  14. Elisabeth Solau-Gervais17,18,
  15. Benjamin Terrier4,
  16. Daniel Wendling19,
  17. Fanny Andry11,
  18. Camille Garnier2,
  19. Pascal Cathébras13,
  20. Laurent Arnaud20,21,
  21. Aurore Palmaro1,3,
  22. Patrice Cacoub7,8,
  23. Zahir Amoura6,
  24. Jean-Charles Piette7,8,
  25. Philippe Arlet2,
  26. Maryse Lapeyre-Mestre1,3,22,
  27. Laurent Sailler1,2,3
  1. 1UMR 1027, INSERM, University of Toulouse, Toulouse, France
  2. 2Department of Internal Medicine, Toulouse University Hospital, Toulouse, France
  3. 3Clinical Investigation Center 1436, Toulouse University Hospital, Toulouse, France
  4. 4Department of Internal Medicine, National Referral Center for Rare and Systemic Autoimmune Diseases, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, University Paris Descartes, Paris, France
  5. 5INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France
  6. 6Department of Internal Medicine 2, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
  7. 7Department of Internal Medicine and Clinical Immunology, Assistance Publique- Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  8. 8UMR 7211, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Université, UPMC Université Paris 06, Paris, France
  9. 9Department of Internal Medicine, Caen University Hospital, Caen, France
  10. 10Department of Internal Medicine, Nantes University Hospital, Nantes, France
  11. 11Department of Internal Medicine, Grenoble University Hospital, Grenoble, France
  12. 12Department of Internal Medicine, Dijon University Hospital, Dijon, France
  13. 13Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Priest-en-Jarez, France
  14. 14Department of Internal Medicine, Nice University Hospital, Nice, France
  15. 15Department of Internal Medicine, Montpellier University Hospital, Montpellier, France
  16. 16Department of Internal Medicine and Clinical Immunology, Saint-Antoine University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
  17. 17Department of Rheumatology, Poitiers University Hospital, Poitiers, France
  18. 18Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, Poitiers University, Poitiers, France
  19. 19Department of Rheumatology, Besançon University Hospital, Besançon, France
  20. 20Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France
  21. 21Laboratoire d’ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Strasbourg University, Strasbourg, France
  22. 22Department of Clinical and Medical Pharmacology, Toulouse University Hospital, Toulouse, France
  1. Correspondence to Dr Guillaume Moulis, UMR 1027 INSERM-UPS, Pharmacoepidemiology unit, Faculté de Médecine, Toulouse 31000, France; moulis.g{at}chu-toulouse.fr

Abstract

Objectives To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP).

Methods We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response.

Results This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs.

Conclusions This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.

  • relapsing polychondritis
  • biologics

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors GM, GP, ML-M and LS designed the study. All other authors included patients into the study. GM and AP conducted the statistical analyses. GM, GP, ML-M and LS interpreted the results and drafted the manuscript. All authors reviewed the manuscript and gave their approval for submission.

  • Funding This study was funded by Toulouse University Hospital.

  • Competing interests GM received a travel grant from Abbvie in 2013 and Amgen in 2017 and received research grants from Novartis, CSL Behring and the Institut Servier in 2016 and 2017. GP received travel support and lecture fees from Abbvie. DW received speaking fees and membership on the advisory boards of the following societies: AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, SOBI, Sanofi Aventis, Novartis, Janssen, Celgene, Hospira, Lilly and Sandoz; he received grants/hospitality from Abbvie, Pfizer, Roche Chugai, MSD and UCB. BT received travel support from Roche and LFB, and received consulting fees from Roche, GSK, LFB and Grifols. PC received consulting and lecturing fees from Abbvie, Astra Zeneca, Bristol-Myers Squibb, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Roche, Servier and Vifor.

  • Patient consent Not required.

  • Ethics approval This study received approval from the Toulouse University Ethics Committee in 2013, and according to French law from the Comité Consultatif du Traitement de l’Information et de la Recherche en Santé (n°13.251) in 2013 and then authorisation from the Commission Nationale de l’Informatique et des Libertés (n°DR-2013-378) in 2013.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. Author Arsène Mékinian’s name has been corrected.

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