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. 2024 Aug 22:15:1445680.
doi: 10.3389/fimmu.2024.1445680. eCollection 2024.

Use of Janus kinase inhibitors before and after European Medicines Agency safety recommendations: a retrospective study

Patrick-Pascal Strunz #  1 , Linus Maximilian Risser #  2 , Matthias Englbrecht  3 , Torsten Witte  2 , Matthias Froehlich  1 , Marc Schmalzing  1 , Michael Gernert  1 , Sebastian Hueper  4 , Peter Bartz-Bazzanella  5   6   7 , Cay von der Decken  5   6   7   8 , Kirsten Karberg  7   9 , Georg Gauler  7   10 , Susanna Späthling-Mestekemper  7   11 , Christoph Kuhn  7   12 , Wolfgang Vorbrüggen  7   8 , Martin Welcker  7   13 , Stefan Kleinert  1   7   14
Affiliations

Use of Janus kinase inhibitors before and after European Medicines Agency safety recommendations: a retrospective study

Patrick-Pascal Strunz et al. Front Immunol. .

Abstract

Background: Safety recommendations for Janus kinase inhibitors (JAKi) issued by the European Medical Agency (EMA) in 2023 could potentially influence treatment patterns for rheumatoid arthritis (RA) drugs, but little is known about the impact of these recommendations in routine clinical care.

Methods: We retrospectively analyzed the German RHADAR rheumatology database for adult patients with RA and documentation of a new therapy with a JAKi, tumor necrosis factor inhibitor (TNFi), or interleukin-6 receptor inhibitor (IL-6Ri). Data were grouped into half-yearly intervals from quarter (Q)2/2020 to Q3/2023. The period from Q4/2022 to Q1/2023 immediately followed the initial EMA endorsement of Pharmacovigilance Risk Assessment Committee (PRAC) recommendations and Q2/2023-Q3/2023 immediately followed the direct healthcare provider communication (DHPC) containing the new safety JAKi recommendations.

Results: Between April 1, 2020 and September 23, 2023, 3008 newly initiated therapies for TNFi (1499 [49.8%]), JAKi (1126 [37.4%]), and IL-6Ri (383 [12.7%]) were documented by the treating physicians. JAKi were increasingly used in the first two half-year periods (from 29.7% of these therapies in Q2/2020-Q3/2020 to 46.7% in Q2/2021-Q3/2021; odds ratio [OR] 2.08; p<0.001). The proportion of initiated JAKi therapies decreased significantly after the PRAC recommendations (32.9%; OR vs peak 0.56; p=0.001) and the DHPC letter (26.1%; OR vs peak 0.40; p<0.001). JAKi were more likely to be used as >3rd-line therapy in later time periods.

Conclusions: This exploratory study suggests that EMA safety recommendations for JAKi influenced treatment patterns of RA patients who received JAKi in Germany. Additional studies will be needed to confirm these findings.

Keywords: cancer; interleukin-6 receptor inhibitors; major adverse cardiac event; oral surveillance; rheumatoid arthritis; treatment; tumor necrosis factor inhibitors; venous thromboembolism.

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Conflict of interest statement

P-PS received research funding from Chugai and speaker’s fees or travel grants from AbbVie, Boehringer/Ingelheim, Eli Lilly, Galapagos, and Janssen-Cilag. LR received travel/meeting support from AbbVie and Biocon Biologics Germany. ME received funding for the present study for data analysis from RHADAR GbR and also received consulting fees from AbbVie and RHADAR, speaker’s fees from AbbVie, Janssen-Cilag, Sanofi, and Swedish Orphan Biovitrum, and is on the advisory board of Chugai Pharma Germany. TW received consulting and/or speaker’s fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chugai, Fresenius Kabi, Galapagos, GSK, Janssen, Lilly, Medac, Nordic, Novartis, Sanofi, and UCB and travel/meeting support from AbbVie, Janssen, Lilly, and UCB. MF received consulting fees or travel/meeting support from AbbVie, Amgen, AstraZeneca, Eli Lilly, Novartis, Janssen, Hexal, Pfizer, Takeda, and UCB. MS received research grants from Chugai and Novartis, consulting and/or speaker’s fees from AbbVie, Alfasigma/Galapagos/Gilead, Amgen, AstraZeneca, BMS, Boehringer/Ingelheim, Chugai/Roche, EUSA-Pharma, Hexal/Sandoz, Janssen-Cilag, Lilly, Novartis, onkowissen.de, and UCB, travel/meeting support from Alfasigma/Galapagos, Boehringer/Ingelheim, Celgene, Chugai/Roche, Medac, Mylan, and UCB, participates on advisory boards for AbbVie, Alfasigma/Galapagos/Gilead, Amgen, AstraZeneca, Boehringer/Ingelheim, Chugai/Roche, EUSA-Pharma, Hexal/Sandoz, Janssen-Cilag, Lilly, Novartis, onkowissen.de, and UCB, and has a leadership role in the Deutsches Netzwerk Systemische Sklerodermie DNSS. MG receive grants from AbbVie, Eli Lilly, and Pfizer, consulting fees from Amgen, AstraZeneca, Novartis, and Takeda, speaker’s fees from AbbVie, Eli Lilly, Janssen, and Novartis, and travel/meeting support from AbbVie, Eli Lilly, Pfizer, and UCB. SH received speaker’s fees from AbbVie and travel/meeting support from Janssen-Cilag and UCB. PB-B received speaker’s fees from AbbVie, Boehringer Ingelheim, Chugai/Roche, Janssen-Cilag, Novartis, Pfizer, and UCB and travel/meeting support from AbbVie. CV received travel/meeting support from AbbVie and Galapagos/Alpha sigma. KK received speaker’s fees from AbbVie, Galapagos, Novartis, Rheumakademie, and UCB and travel/meeting support from UCB. GG received speaker’s fees from AbbVie, Galapagos, and Novartis and travel/meeting support from AbbVie and Novartis. SS-M received speakers fees from AbbVie, Boehringer Ingelheim, Eli Lilly, GSK, Janssen-Cilag, Novartis, and UCB. WV received travel support from Bundesverband Managed Care. MW received consulting and/or speaker’s fees from AbbVie, Fresenius, Galapagos, Lilly, and UCB and travel/meeting support from AbbVie, Galapagos, GSK, Lilly, and UCB. SK received grants from AbbVie, Novartis, and Sparrow, and consulting and/or speaker’s fees from AbbVie, Celgene, Chugai, Galapagos, Novartis, and Siemens Healthineers. PB-B, CvdD, KK, GG, SS-M, CK, WV, MW, and SK are members of RheumaDatenRhePort RHADAR GbR.

Figures

Figure 1
Figure 1
Changes in initiation of JAKi therapy in the time periods before and after JAKi EMA safety recommendations. (A) Proportion of new therapies initiated with JAKi, TNFi, or IL-6Ri; (B) Odds ratios (95% CI) and statistical significance of changes in proportions of newly initiated JAKi treatment over time. Green shading indicates significant increases in the proportion of JAKi therapies and red shading indicates significant decreases in the proportion of JAKi therapies. P values were calculated using the Benjamini-Hochberg adjustment. CI, confidence interval; DHPC, direct healthcare provider communication; EMA, European Medical Agency; IL-6Ri, interleukin-6 receptor inhibitor; JAKi, Janus kinase inhibitor; PRAC, Pharmacovigilance Risk Assessment Committee recommendations; Q, quarter; TNFi, tumor necrosis factor inhibitor.
Figure 2
Figure 2
Changes in line of therapy in patients initiating JAKi treatment before and after JAKi EMA safety recommendations. DHPC, direct healthcare provider communication; EMA, European Medical Agency; JAKi, Janus kinase inhibitor; PRAC, Pharmacovigilance Risk Assessment Committee recommendations.
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