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After JAK inhibitor failure: to cycle or to switch, that is the question – data from the JAK-pot collaboration of registries
  1. Manuel Pombo-Suarez1,
  2. Carlos Sanchez-Piedra2,
  3. Juan Gómez-Reino3,
  4. Kim Lauper4,5,
  5. Denis Mongin4,
  6. Florenzo Iannone6,
  7. Karel Pavelka7,
  8. Dan C Nordström8,
  9. Nevsun Inanc9,
  10. Catalin Codreanu10,
  11. Kimme L Hyrich5,11,
  12. Denis Choquette12,
  13. Anja Strangfeld13,14,
  14. Burkhard F Leeb15,16,
  15. Ziga Rotar17,18,
  16. Ana Rodrigues19,
  17. Eirik Klami Kristianslund20,
  18. Tore K Kvien20,
  19. Ori Elkayam21,
  20. Galina Lukina22,
  21. Sytske Anne Bergstra23,
  22. Axel Finckh4,
  23. Delphine Sophie Courvoisier4
  1. 1Rheumatology Department, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
  2. 2Health Technology Assessment Agency, Instituto de Salud Carlos III, Madrid, Spain
  3. 3Fundacion IDIS, Hospital Clinico Universitario, Santiago de Compostela, Spain
  4. 4Division of Rheumatology, Department of Internal Medicine and Department of Medicine, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
  5. 5Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  6. 6GISEA, DETO Rheumatology Unit, University of Bari, Bari, Italy
  7. 7Department of Rheumatology, Charles University, Praha, Czech Republic
  8. 8ROB-FIN, Departments of Medicine and Rheumatology, Helsinki University Hospital and Helsinki University, Helsinki, Finland
  9. 9Division of Rheumatology, Marmara University School of Medicine, Istanbul, Turkey
  10. 10Rheumatology, Center of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania
  11. 11NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  12. 12Institut de Recherche en Rhumatologie de Montréal, University of Montreal, Montreal, Quebec, Canada
  13. 13Epidemiology Unit, German Rheumatism Research Center (DRFZ), Berlin, Germany
  14. 14Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany
  15. 15BioReg, Vienna, Austria
  16. 16Private Office, Hollabrunn, Austria
  17. 17Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
  18. 18Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  19. 19Unidade de Reumatologia, Hospital Lusiadas, Lisbon, Portugal
  20. 20Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway
  21. 21Department of Rheumatology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  22. 22VA Nasonova Research Institute of Rheumatology, AS Loginov Moscow Clinical Scientific Center, RBITER, Institute of Rheumatology, Moscow, Russian Federation
  23. 23Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Manuel Pombo-Suarez, Rheumatology Department, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela 15706, Spain; mpombosuarez{at}gmail.com

Abstract

Objectives The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi.

Methods This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders.

Results 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies.

Conclusions After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

  • Arthritis, Rheumatoid
  • Therapeutics
  • Antirheumatic Agents

Data availability statement

Data are available upon reasonable request. All the data belong to the registers. Anonymised data can be shared as long as agreements are made with all participating registers.

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Data availability statement

Data are available upon reasonable request. All the data belong to the registers. Anonymised data can be shared as long as agreements are made with all participating registers.

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Footnotes

  • Handling editor Josef S Smolen

  • Twitter @delcourvoisier

  • Presented at Some of the data contained in this manuscript have been previously presented in one abstract: Pombo-Suarez M, Sanchez-Piedra C, Gomez-Reino J et al. Effectiveness of cycling JAKi compared to switching to bDMARD in patients who failed a first JAKi in an international collaboration of registries of rheumatoid arthritis patients (the JAK-pot study). Arthritis Rheumatol 2021;73 (suppl 10).

  • Contributors All the authors have provided substantial contribution to the conception or design of the work, the acquisition of the data and the interpretation of data. DSC and CS-P performed the statistical analysis. MP-S, DSC, JG-R and CS-P made the first draft. All the other authors participated in the final drafting of the work or revising it critically for important intellectual content. All authors contributed to the final approval of the version published. MP-S and DSC accept full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding The JAK-pot consortium is an investigator-initiated collaboration initially funded by an unrestricted research grant by Pfizer and later also by AbbVie and Galapagos. These companies had no influence on the research questions, results and conclusions. The sponsor did not participate in the collection or analysis of data and did not have access to the data.

  • Competing interests MP-S reports personal fees from Janssen, Merck Sharp & Dohme, Novartis and Sanofi Genzyme, outside the submitted work. CS-P has nothing to disclose. JG-R has been a consultant on advisory boards of AbbVie, Bristol Myers Squibb, Hospira, Janssen, Merck Sharp & Dohme, Pfizer, Regeneron, Roche and Sanofi Genzyme, and has received research grants from Pfizer and Roche. KL reports personal fees from Viatris, Pfizer, Celltrion and Gilead/Galapagos, outside the submitted work. DM has nothing to disclose. FI has received speaker and/or consultancy fees from AbbVie, Galapagos, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche and UCB. KP has received fees for lectures and consultations from AbbVie, Pfizer, Merck Sharp & Dohme, UCB, Eli Lilly, SOBI, Roche, Sanofi Genzyme, Celltrion, Viatris and Novartis. DCN reports speaker and consultancy fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer and UCB. NI reports grants from Roche and Pfizer, and personal fees from AbbVie, Roche, Pfizer, UCB, Novartis, Amgen, Eli Lilly and Merck Sharp & Dohme. CC has received clinical trial expenses from AbbVie, Ewopharma, Eli Lilly, Novartis and Pfizer, and speaker and consultancy fees from AbbVie, Boehringer Ingelheim, Ewopharma, Eli Lilly, Novartis, Pfizer, Sandoz and UCB. KLH has received speaker fees from AbbVie and grants from Pfizer and Bristol Myers Squibb and is also supported by the NIHR Manchester Biomedical Research Centre. DC has received consultant and speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Fresenius Kabi, Pfizer, Novartis, Sandoz and Tevapharm. AS has received speaker/honoraria from AbbVie, Celltrion, Merck Sharp & Dohme, Roche, Bristol Myers Squibb and Pfizer. BFL has received clinical trial expenses from TRB and Roche, consultancy fees from AbbVie, Amgen, Roche, Merck Sharp & Dohme, Pfizer, Celgene, Grünenthal, Kwizda, Eli Lilly, Novartis and Sandoz, and speaker fees from AbbVie, Roche, Merck Sharp & Dohme, Pfizer, Actiopharma, Boehringer Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal and Eli Lilly. ZR reports speaker and consultancy fees from AbbVie, Amgen, Biogen, Pfizer, Merck Sharp & Dohme, Roche, Novartis, Sanofi Genzyme, Medis, Eli Lilly and Sandoz. AR reports personal fees from Amgen, Pfizer and AstraZeneca, outside the submitted work. EKK reports no competing interests. TKK has received fees for speaking and/or consulting from AbbVie, Amgen, Celltrion, Egis, Eva Pharma, Ewopharma, Gilead, Hikma, Janssen, Mylan, Novartis, Oktal, Pfizer, Sandoz and UCB, and received research funding to Diakonhjemmet Hospital from AbbVie, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer and UCB. OE has received clinical trial expenses from AbbVie, Pfizer, Novartis, Eli Lilly and Janssen, and speaker fees from AbbVie, Pfizer, Roche, Janssen, Eli Lilly and Novartis. GL has received consultant fees from AbbVie, BIOCAD, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer and R-PHARM. SAB received an ASPIRE grant from Pfizer. AF has received fees for speaking and/or consulting from AbbVie, AstraZeneca, Bristol Myers Squibb, Galapagos, Mylan, Novartis, Pfizer, Sandoz and UCB, and received research funding to Geneva University Hospital from AbbVie, Bristol Myers Squibb, Pfizer and Galapagos. DSC has nothing to disclose. BIOBADASER has received funding from Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency (Agencia Española del Medicamento y Productos Sanitarios) and equal grants from pharmaceutical companies (AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Samsung, Schering-Plough and UCB). The Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database is sponsored by public and industrial support (http://scqm.ch/en/sponsoren/). Clinical work in Czech Republic was partially supported by the project from the Ministry of Health for conceptual development of research organization (MZ00023728023728) (Institute of Rheumatology). ROB-FIN is funded by AbbVie, Hospira, BMS, MSD, Pfizer, Roche and UCB. The Romanian Registry of Rheumatic Diseases (RRBR) uses unrestricted grants from AbbVie, Pfizer, Eli Lilly, Ewopharma, Novartis, MSD, Roche, UCB and BMS. The British Society for Rheumatology Biologics Register in Rheumatoid Arthritis (BSRBR-RA) is funded by a grant from the British Society for Rheumatology (BSR). The BSR currently receives funding from AbbVie, Amgen, Celltrion HC, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi and Sandoz, and in the past Hospira, MSD, Roche, SOBI and UCB. This income finances a wholly separate contract between the BSR and The University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation and publication are made autonomously of any industrial contribution. The BSRBR-RA would like to gratefully acknowledge the support of the National Institute for Health Research through the Local Clinical Research Networks in England (and equivalent organisations in the devolved nations) at participating centres and the BSRBR-RA Control Centre Consortium. Rhumadata is supported by equal unrestricted grants from AbbVie, Amgen, Celgene, Eli Lilly, Fresenius Kabi, Pfizer, Novartis, Sandoz and Tevapharm. The RABBIT register is currently supported by an unconditional grant with equal parts from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB. biorx.si has received equal grants from AbbVie, Amgen, Biogen, Pfizer, Merck Sharp & Dohme, Roche, Novartis, Mylan, Sanofi Genzyme, Medis, Eli Lilly, Sandoz and Medis. Reuma.pt has received funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer. NOR-DMARD has been supported with research funding to Diakonhjemmet Hospital from AbbVie, Amgen, BMS, MSD, Novartis, Pfizer and UCB.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

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