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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

M. Pombo-Suarez, C. Sanchez-Piedra, J. Gómez-Reino, K. Lauper, D. Mongin, F. Iannone, K. Pavelka, DC. Nordström, N. Inanc, C. Codreanu, KL. Hyrich, D. Choquette, A. Strangfeld, BF. Leeb, Z. Rotar, A. Rodrigues, EK. Kristianslund, TK. Kvien, O....

. 2023 ; 82 (2) : 175-181. [pub] 20220913

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc23004445

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.

BioReg Vienna Austria

Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre Manchester UK

Department of Rheumatology and Clinical Immunology Charité University Medicine Berlin Germany

Department of Rheumatology Charles University Praha Czech Republic

Department of Rheumatology Leiden University Medical Center Leiden The Netherlands

Department of Rheumatology Tel Aviv Sourasky Medical Center Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Department of Rheumatology University Medical Centre Ljubljana Slovenia

Division of Rheumatology and Research Diakonhjemmet Hospital Oslo Norway

Division of Rheumatology Department of Internal Medicine and Department of Medicine Faculty of Medicine Geneva University Hospitals Geneva Switzerland

Division of Rheumatology Marmara University School of Medicine Istanbul Turkey

Epidemiology Unit German Rheumatism Research Center Berlin Germany

Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Fundacion IDIS Hospital Clinico Universitario Santiago de Compostela Spain

GISEA DETO Rheumatology Unit University of Bari Bari Italy

Health Technology Assessment Agency Instituto de Salud Carlos 3 Madrid Spain

Institut de Recherche en Rhumatologie de Montréal University of Montreal Montreal Quebec Canada

NIHR Manchester Biomedical Research Centre Manchester University NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK

Private Office Hollabrunn Austria

Rheumatology Center of Rheumatic Diseases University of Medicine and Pharmacy Bucharest Romania

Rheumatology Department Complejo Hospitalario Universitario de Santiago de Compostela Santiago de Compostela Spain

ROB FIN Departments of Medicine and Rheumatology Helsinki University Hospital and Helsinki University Helsinki Finland

Unidade de Reumatologia Hospital Lusiadas Lisbon Portugal

VA Nasonova Research Institute of Rheumatology AS Loginov Moscow Clinical Scientific Center RBITER Institute of Rheumatology Moscow Russian Federation

References provided by Crossref.org

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$a 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.
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