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Observational Study
. 2024 Mar 12;83(4):421-428.
doi: 10.1136/ard-2023-224670.

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study)

Romain Aymon  1 , Denis Mongin  2 , Sytske Anne Bergstra  3 , Denis Choquette  4 , Catalin Codreanu  5 , Diederik De Cock  6 , Lene Dreyer  7 , Ori Elkayam  8 , Doreen Huschek  9 , Kimme L Hyrich  10   11 , Florenzo Iannone  12 , Nevsun Inanc  13 , Lianne Kearsley-Fleet  10 , Suleyman Serdar Koca  14 , Tore K Kvien  15 , Burkhard F Leeb  16 , Galina Lukina  17 , Dan C Nordström  18 , Karel Pavelka  19 , Manuel Pombo-Suarez  20 , Ana Rodrigues  21 , Ziga Rotar  22 , Anja Strangfeld  9 , Patrick Verschueren  23 , Rasmus Westermann  7 , Jakub Zavada  19 , Delphine Sophie Courvoisier  24 , Axel Finckh  24 , Kim Lauper  24
Affiliations
Observational Study

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study)

Romain Aymon et al. Ann Rheum Dis. .

Abstract

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.

Keywords: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Therapy; Epidemiology.

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Conflict of interest statement

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 Grünenthal, Sandoz and speaker fees from Grünenthal, 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.

Figures

Figure 1
Figure 1
Crude cumulative incidence of stopping for adverse events. JAKi, Janus kinase inhibitors; OMA, biological disease-modifying rheumatic drugs with other modes of action; TNFi, tumour necrosis factor inhibitors
Figure 2
Figure 2
Adjusted cause-specific HRs (csHR) of stopping for AEs for TNFi and OMA against reference JAKi, in the overall cohort and in the different subgroups. AE, adverse event; csHR, cause-specific HR; JAKi, Janus kinase inhibitors; OMA, biological disease-modifying rheumatic drugs with other modes of action; RCT, randomised controlled trial; TNFi, tumour necrosis factor inhibitors.
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