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. 2020 Nov;6(3):e001374.
doi: 10.1136/rmdopen-2020-001374.

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research

Andreas Kerschbaumer  1 , Josef S Smolen  2 , Peter Nash  3 , Thomas Doerner  4 , Maxime Dougados  5 , Roy Fleischmann  6 , Klaus Geissler  7 , Iain B McInnes  8   9 , Tsutomu Takeuchi  10 , Michael Trauner  11 , Kevin Winthrop  12 , Maarten de Wit  13 , Wolf-Henning Boehncke  14 , Louise Falzon  15 , Desirée van der Heijde  16
Affiliations

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research

Andreas Kerschbaumer et al. RMD Open. 2020 Nov.

Abstract

Objectives: Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs).

Methods: A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation.

Results: 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed.

Conclusion: JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.

Keywords: Arthritis; ankylosing; lupus erythematosus; psoriatic; rheumatoid; spondylitis; systemic.

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Conflict of interest statement

Competing interests: AK: Speakers bureau: Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer; non-financial support: Gilead. JSS: Amgen, AbbVie, AstraZeneca, Astro, BMS, Celgene, Glaxo, ILTOO, Janssen, Merck-Serono, MSD, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, UCB. PN: AbbVie, BMS, UCB, Lilly, Gilead/Galapagos, Pfizer, GSK, Roche, Sanofi, Janssen, MSD, Novartis, Boehringer-Ingelheim, Celgene, Samsung. TD: AbbVie, BMS, Celgene, Eli Lilly, Janssen, EMD Merck-Serono, Galapagos, Gilead, Novartis, Roche, Samsung, UCB. MD: AbbVie, Biogen, Celgene, Janssen, Lilly, Novartis, Merck, Pfizer, Sanofi-Aventis, UCB. RF: Consultant: AbbVie, Acea, Akros, Amgen BMS, Celltrion, Gilead, GSK, Jansen, Eli Lilly, Novartis, Pfizer, Samsung, Sanofi-Aventis, Tahio, UCB; Data Safety Monitoring Boards EMDSerano, Celltrion; Clinical Trial Grants: AbbVie, Acea, Akros, Amgen, AstraZeneca, BMS, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi-Aventis, UCB. KG has received consultancy and lecture fees from Novartis, Pfizer and Roche and investigational grants from Roche. IBM has received research funding or honoraria from AbbVie, AstraZeneca, Celgene, GSK, Lilly, Boehringer, Pfizer, Janssen, Novartis, UCB, BMS, Sanofi. TT: AbbVie GK, Astellas, Asahi Kasei, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Pfizer Japan, Nippon Kayaku and Takeda. MT: speaker fees from Bristol-Myers Squibb (BMS), Falk Foundation, Gilead, Intercept and Merck Sharp & Dohme (MSD); advisory board fees from Albireo, Boehringer Ingelheim, BiomX, Falk Pharma GmbH, GENFIT, Gilead, Intercept, MSD, Novartis, Phenex, and Regulus; travel grants from AbbVie, Falk, Gilead, and Intercept; and research grants from Albireo, CymaBay, Falk, Gilead, Intercept, MSD, and Takeda. He is also coinventor of patents on the medical use of norUDCA filed by the Medical University of Graz. KW: Research grants from BMS, Pfizer; Consulting fees: AbbVie, BMS, Eli Lilly, Gapalagos, Gilead, Pfizer, UCB, Regeneron, GSK, and Roche; MdW has received honoraria for consultancies and speaking through Stichting Tools from AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Roche. W-HB has received a research grant from Pfizer and honoraria for advice from AbbVie, Alimirall, BMS, Celgene, Janssen, Leo, Lilly, Novartis and UCB. LF: Nothing to declare. DvdH: Consulting fees: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Director of Imaging Rheumatology BV.

Figures

Figure 1
Figure 1
PRISMA flow chart for studies on JAKi efficacy and/or safety in inflammatory immune disease, published until March 2019. JAKi, Janus kinase inhibitors; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Efficacy of Janus kinase inhibiting agents across immune-mediated diseases (based on available data at end of March 2019). JAK, Janus kinase.
See this image and copyright information in PMC

References

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