Clinical efficacy of new JAK inhibitors under development. Just more of the same?

Rheumatology
Rene Westhovens

Abstract

Janus kinase inhibition is promising in the treatment of RA, with already two oral drugs marketed. New compounds are under investigation that are more selective for Janus kinase 1 or Janus kinase 3. Phase II results for filgotinib, upadacitinib, peficitinib and decernotinib are reviewed showing almost consistently a fast dose-dependent clinical improvement similar to already approved drugs tofacitinib and baricitinib. I will reflect on the most frequently reported dose-dependent adverse events and laboratory changes. Some are similar for all drugs of this class, some are more specific for a certain drug, but all may influence future treatment effectiveness in daily practice. This implies the need for a critical evaluation of phase III trials, and eventually trials specifically powered for conclusions on the safety profile and registries once these drugs become marketed. These innovative drugs also need head-to-head trials versus biologics or in-class as well as specific strategy studies to determine their optimal future use.

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Citations

Jul 3, 2019·Journal of Clinical Medicine·Birgit M KöhlerHanns-Martin Lorenz
Sep 6, 2019·Journal of Cellular Physiology·Nicola MaruottiFrancesco Paolo Cantatore
Apr 30, 2020·Expert Opinion on Pharmacotherapy·Yoshiya Tanaka, Hiroyuki Izutsu
Jun 10, 2020·Expert Opinion on Pharmacotherapy·Eduardo Mysler, Ana Lizarraga
May 6, 2020·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Vijayabhaskar VeeravalliNuggehally R Srinivas
Jul 14, 2020·Therapeutic Advances in Musculoskeletal Disease·Flavia SunziniStefan Siebert
Sep 16, 2020·International Journal of Molecular Sciences·Jan AmrheinJessica Bertrand
Jun 20, 2020·Clinical Reviews in Allergy & Immunology·Jiao JiangQianjin Lu
Jan 26, 2021·Expert Review of Clinical Pharmacology·Ogugua Ndili ObiRobert P Baughman
Feb 23, 2021·Frontiers in Medicine·Rita A Moura, João Eurico Fonseca
May 7, 2021·Frontiers in Pharmacology·Yannick VandenplasIsabelle Huys
Jun 15, 2021·Frontiers in Pharmacology·Shahin ShamsJudith F Ashouri
Aug 30, 2021·Lancet·Donal P McLornanClaire N Harrison
Dec 21, 2021·Journal of Medicinal Chemistry·Christopher R WellawayDiane M Coe

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