POS0390 POTENTIAL IMPACT OF EMA RISK MINIMISATION MEASURES WITH JAKi ON CURRENT JAKi PRESCRIBING IN UK
Authors: Z. Tian, L. Kearsley-Fleet, J. Galloway, K. Watson, M. Lunt, B. R. Contributors Group, K. Hyrich
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Janus kinase inhibitors (JAKi) are effective therapies for the management of rheumatoid arthritis (RA). However, concerns about their safety in certain "at-risk" populations have resulted in risk minimisation measures being introduced by the European Medicines Agency (EMA) in January 2023, which limits prescription of JAKi to certain patient subgroups unless no suitable alternative is available. The potential impact of these measures on current and future JAKi use in the UK is unknown. <h3>Objectives:</h3> Using a large national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion of patients who met one or more of these criteria and therefore may be impacted by these changes. <h3>Methods:</h3> All RA patients who started their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the BSRBR-RA before 31<sup>st</sup> May 2022 were included. This cutoff date preceded the EMA warning [1]. Patients with missing data in any EMA criteria related variables were excluded from the analysis. Descriptive statistics were used to present patients' characteristics at the start of their first-ever JAKi. This analysis defined four at-risk criteria assessed at the start of treatment: 1) aged ≥65 years, 2) increased risk of major cardiovascular problems (history of ischaemic heart disease, stroke, dyslipidaemia, hypertension or diabetes), 3) current or past smokers, 4) increased risk of cancer (defined as prior cancer). Among those who met the criteria, the previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes of therapy was described (i.e. TNF inhibitor, IL-6 inhibitor). <h3>Results:</h3> A total of 1362 patients starting their first JAKi were included, and baricitinib was most common (76%), followed by tofacitinib (16%; Table 1). The cohort was 78% female, with an average age of 60 years. Among them, 28% of patients had received ≥3 prior classes of bDMARDs. Eighty percent of patients (1090) met ≥1 EMA risk criterion, with most common individual criterion as current/past smoker (54%) or cardiovascular risk factors (44%). Of those who met ≥1 risk criteria, 645 (59%) met more than one EMA risk criterion. Additionally, 29% had already received ≥3 prior bDMARDs classes, and 52% of the patients previously receiving ≥2 prior bDMARDs classes. <h3>Conclusion:</h3> We observed that a very high proportion of patients four-in-five commencing JAKi in the UK prior to the EMA advisory would have fallen into the 'high-risk' category for whom prescribing would only be advised if no suitable alternatives were available. Whilst almost a third of those had been treated with three or more prior bDMARDs classes, it is likely that for a substantial proportion, suitable alternatives would have existed. These data highlight the enormous impact of the recent licensing updates for the JAKi class. <h3>REFERENCES:</h3> [1] EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders 2022 [updated 28/10/2022. Available from: https://www.ema.europa.eu/en/news/ema-recommends-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic accessed 28/11/2023 2023. [2] EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders, EMA's human medicines committee (CHMP) 2023 [updated 23 January 2023. Available from: https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki accessed 15 June 2023. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Zixing Tian: None declared, Lianne Kearsley-Fleet: None declared, James Galloway Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, and Vifor, Abbvie, Galapagos, GSK, Janssen and Pfizer, Kath Watson: None declared, Mark Lunt: None declared, BSRBR-RA Contributors Group: None declared, Kimme Hyrich Abbvie, Pfizer, BMS.