PMID- 38071508
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240324
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 83
IP  - 4
DP  - 2024 Mar 12
TI  - Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in 
      an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' 
      study).
PG  - 421-428
LID - 10.1136/ard-2023-224670 [doi]
AB  - BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) 
      taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse 
      events rates compared with those taking the tumour necrosis factor inhibitors 
      (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations 
      for adverse events (AEs) among second-line therapies in an international 
      real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological 
      with another mode of action (OMA) from 17 registers participating in the 
      'JAK-pot' collaboration were included. The primary outcome was the rate of 
      treatment discontinuation due to AEs. We used unadjusted and adjusted 
      cause-specific Cox proportional hazard models to compare treatment 
      discontinuations for AEs among treatment groups by class, but also evaluating 
      separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses 
      included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 
      2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard 
      rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 
      95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), 
      lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher 
      for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus 
      JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 
      95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with 
      more treatment discontinuations for AEs, subgroup analyses suggest varying 
      patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, 
      these observations should be interpreted cautiously, given the observational 
      study design.
CI  - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Aymon, Romain
AU  - Aymon R
AUID- ORCID: 0000-0003-2854-3632
AD  - Rheumatology Division, Geneva University Hospitals, Geneve, Switzerland 
      romain.aymon@hcuge.ch.
FAU - Mongin, Denis
AU  - Mongin D
AUID- ORCID: 0000-0002-4801-8395
AD  - Rheumatology Division, Geneva University Hospitals, Geneve, Switzerland.
FAU - Bergstra, Sytske Anne
AU  - Bergstra SA
AUID- ORCID: 0000-0002-7136-5248
AD  - Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
FAU - Choquette, Denis
AU  - Choquette D
AD  - Institut de recherche en Rhumatologie, CHUM, Montreal, Quebec, Canada.
FAU - Codreanu, Catalin
AU  - Codreanu C
AD  - Center for Rheumatic Diseases, University of Bucharest, Bucuresti, Romania.
FAU - De Cock, Diederik
AU  - De Cock D
AD  - Biostatistics and Medical Informatics Research Group, Department of Public 
      Health, Vrije Universiteit Brussel, Brussel, Belgium.
FAU - Dreyer, Lene
AU  - Dreyer L
AD  - Rheumatology, DANBIO, Aalborg University Hospital, Aalborg, North Denmark Region, 
      Denmark.
FAU - Elkayam, Ori
AU  - Elkayam O
AD  - Rheumatology, Tel Aviv University, Tel Aviv, Israel.
FAU - Huschek, Doreen
AU  - Huschek D
AD  - Programme Area Epidemiology, DRFZ, Berlin, Germany.
FAU - Hyrich, Kimme L
AU  - Hyrich KL
AUID- ORCID: 0000-0001-8242-9262
AD  - Centre for Epidemiology Versus Arthritis, The University of Manchester, 
      Manchester, UK.
AD  - Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research 
      Centre, Manchester, UK.
FAU - Iannone, Florenzo
AU  - Iannone F
AUID- ORCID: 0000-0003-0474-5344
AD  - DiMePRe-J -Rheumatology Unit, University of Bari, Bari, Puglia, Italy.
FAU - Inanc, Nevsun
AU  - Inanc N
AUID- ORCID: 0000-0003-2862-0562
AD  - Rheumatology, Marmara University School of Medicine, Istanbul, Turkey.
FAU - Kearsley-Fleet, Lianne
AU  - Kearsley-Fleet L
AUID- ORCID: 0000-0003-0377-1575
AD  - Centre for Epidemiology Versus Arthritis, The University of Manchester, 
      Manchester, UK.
FAU - Koca, Suleyman Serdar
AU  - Koca SS
AD  - Division of Rheumatology, Firat University, Faculty of Medicine, Elazig, Turkey.
FAU - Kvien, Tore K
AU  - Kvien TK
AD  - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), 
      Diakonhjemmet Hospital, Oslo, Norway.
FAU - Leeb, Burkhard F
AU  - Leeb BF
AD  - Austrian registry for Biologics, Biosimilars und targeted synthetic DMARDs 
      (ts-DMARDs) in the treatment of rheumatic diseases, BioReg, Vienna, Austria.
FAU - Lukina, Galina
AU  - Lukina G
AD  - V.A.Nasonova Research Institute of Rheumatology, A.S.Loginov Moscow Clinical 
      Scientific Center, Moscow, Russian Federation.
FAU - Nordstrom, Dan C
AU  - Nordstrom DC
AD  - Division of Medicine, ROB-FIN, Helsinki University and Helsinki University 
      Hospital, Helsinki, Finland.
FAU - Pavelka, Karel
AU  - Pavelka K
AD  - Rheumatology, Institute of Rheumatology, Praha, Czech Republic.
FAU - Pombo-Suarez, Manuel
AU  - Pombo-Suarez M
AUID- ORCID: 0000-0002-2524-4883
AD  - Rheumatology, Hospital Clinico Universitario, Santiago de Compostela, Spain.
FAU - Rodrigues, Ana
AU  - Rodrigues A
AD  - Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de 
      Medicina de Lisboa, Lisbon, Portugal.
FAU - Rotar, Ziga
AU  - Rotar Z
AD  - Department of Rheumatology & University of Ljubljana, Faculty of Medicine, 
      University Medical Centre Ljubljana, Ljubljana, Ljubljana, Slovenia.
FAU - Strangfeld, Anja
AU  - Strangfeld A
AUID- ORCID: 0000-0002-6233-022X
AD  - Programme Area Epidemiology, DRFZ, Berlin, Germany.
FAU - Verschueren, Patrick
AU  - Verschueren P
AUID- ORCID: 0000-0002-0340-3580
AD  - Skeletal Biology and Engineering research Center, KU Leuven, Leuven, Flanders, 
      Belgium.
FAU - Westermann, Rasmus
AU  - Westermann R
AD  - Rheumatology, DANBIO, Aalborg University Hospital, Aalborg, North Denmark Region, 
      Denmark.
FAU - Zavada, Jakub
AU  - Zavada J
AD  - Rheumatology, Institute of Rheumatology, Praha, Czech Republic.
FAU - Courvoisier, Delphine Sophie
AU  - Courvoisier DS
AUID- ORCID: 0000-0002-1956-2607
AD  - Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland.
FAU - Finckh, Axel
AU  - Finckh A
AUID- ORCID: 0000-0002-1210-4347
AD  - Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland.
FAU - Lauper, Kim
AU  - Lauper K
AUID- ORCID: 0000-0002-4315-9009
AD  - Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20240312
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - ISP4442I3Y (baricitinib)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Necrosis Factor Inhibitors)
RN  - 0 (Azetidines)
RN  - 0 (Purines)
RN  - 0 (Pyrazoles)
RN  - 0 (Sulfonamides)
SB  - IM
MH  - Humans
MH  - *Antirheumatic Agents/therapeutic use
MH  - *Janus Kinase Inhibitors/therapeutic use
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha
MH  - *Arthritis, Rheumatoid/drug therapy
MH  - Tumor Necrosis Factor Inhibitors/therapeutic use
MH  - *Azetidines
MH  - *Purines
MH  - *Pyrazoles
MH  - *Sulfonamides
PMC - PMC10958307
OTO - NOTNLM
OT  - Antirheumatic Agents
OT  - Arthritis, Rheumatoid
OT  - Biological Therapy
OT  - Epidemiology
COIS- Competing interests: RA has nothing to disclose. DM has nothing to disclose. SAB 
      reports grants from Pfizer outside of this work and speaker fees from Benecke. DC 
      has nothing to disclose. CC reports reports personal fees from AbbVie, Amgen, 
      Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer outside the submitted 
      work. DDC has nothing to disclose. LD reports contract with BMS outside the 
      present work. OE reports consulting and speaker fees from AbbVie, Pfizer, Eli 
      Lilly, Novartis and Jansen. DH has nothing to disclose. KLH reports grant support 
      from Pfizer and Bristol Myers Squibb and speaking fees from AbbVie. FI reports 
      consulting fees from AbbVie, Janssen, UCB, Galapagos and speaker fees from 
      AbbVie, Galapagos, Eli Lilly, Pfizer and UCB. NI reports consulting and speaking 
      fees from AbbVie, Novartis, UCB, Eli Lilly, Pfizer and Celltrion. LKF has nothing 
      to disclose. SSK has nothing to disclose. TKK reports grants from AbbVie, BMS, 
      Galapagos, Novartis, Pfizer and UCB, consulting fees from AbbVie, Gilead, 
      Janssen, Novartis, Pfizer, Sandoz, UCB Grunenthal, Sandoz and speaker fees from 
      Grunenthal, Sandoz. BFL reports consulting fees from Eli Lilly, Pfizer and 
      AbbVie, and speaking fees from Sandoz. GL has nothing to disclose. DN reports 
      grants from MSD, consulting fees from BMS, Lilly, Novartis, Pfizer, UCB and 
      speaker fees from Pfizer and UCB. KP reports speaker fees from Novartis, Eli 
      Lilly, Roche, Pfizer, Sobi, AbbVie, Pfizer and MSD. MPS has nothing to disclose. 
      AR reports grants from Amgen, AstraZeneca, Novartis, AbbVie, Pfizer, MSD, Lilly, 
      Boehringer Ingelheim, speaker fees from Amgen, AbbVie and Novartis. ZR reports 
      consulting fees from AbbVie, Pfizer, Janssen, AstraZeneca, Novartis, Boehringer 
      Ingelheim, Eli Lilly and speaker fees from AbbVie, Pfizer, Janssen, AstraZeneca, 
      Novartis, Boehringer Ingelheim, Eli Lilly, SOBI, Lek (Sandoz). AS reports speaker 
      fees from AbbVie, BMC, MSD, Pfizer and Roche. PV reports grants from Pfizer and 
      Galapagos, consulting fees from Galapagos, Gilead, Pfizer, Sidekick Health, 
      speaking fees from Eli Lilly, Galapagos and Roularta. RW has nothing to disclose. 
      JZ reports speaking fees from AbbVie, Sobi, Pfizer and Eli Lilly. DSC reports 
      consulting fees from Medela AG. AF reports grants from AbbVie, Pfizer, Galapagos 
      and Eli Lilly, consulting fees from Eli Lilly, Pfizer, AbbVie, speaker fees from 
      Pfizer, Eli Lilly, AbbVie, MSD and BMS. KL has received consultancy and/or 
      speaker fees from Pfizer, Viatris, Celltrion and Galapagos paid to her 
      institution.
EDAT- 2023/12/10 08:41
MHDA- 2024/03/14 06:47
PMCR- 2024/03/22
CRDT- 2023/12/10 05:43
PHST- 2023/07/06 00:00 [received]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2024/03/14 06:47 [medline]
PHST- 2023/12/10 08:41 [pubmed]
PHST- 2023/12/10 05:43 [entrez]
PHST- 2024/03/22 00:00 [pmc-release]
AID - ard-2023-224670 [pii]
AID - 10.1136/ard-2023-224670 [doi]
PST - epublish
SO  - Ann Rheum Dis. 2024 Mar 12;83(4):421-428. doi: 10.1136/ard-2023-224670.