OA05 Potential impact of European Medicines Agency measures to minimise risk of serious side effects on those using JAK inhibitors in the UK

Janus kinase inhibitors (JAKi) are effective therapies for rheumatoid arthritis (RA). However, concerns about their safety in certain 'at-risk' populations have resulted in risk minimisation measures introduced by European Medicines Agency (EMA) in January 2023, which limits JAKi prescription to certain patient subgroups unless no suitable alternative is available. The potential impact on current and future JAKi use in the UK is unknown. Using a national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion meeting ≥1 of these criteria and therefore may be impacted by these changes.

RA patients starting their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the British Society for Rheumatology RA Biologics Register (BSRBR-RA) before 31^st May 2022 (pre-EMA warning) were included. Patients with missing data in any EMA criteria related variables were excluded. Descriptive statistics were used to present patients' characteristics at the start of JAKi. This analysis defined four at-risk criteria assessed at the treatment start: 1) aged ≥65; 2) increased risk of major cardiovascular issues (history of hypertension, hyperlipidaemia, diabetes, ischaemic heart disease, or stroke); 3) current or past smokers; 4) increased risk of cancer (defined as prior cancer). The previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes was described among those who met the criteria.

A total of 1,362 patients starting their first JAKi were included, most commonly baricitinib (76%), followed by tofacitinib (16%; see Table). The cohort was 78% female, with an average age of 60. Among them, 28% of patients had received ≥3 prior bDMARDs classes. 80% percent of patients (1,090) met ≥1 EMA risk criterion, with the most common individual criterion current/past smoker (54%). Of those who met ≥1 risk criteria, 645 (59%) met ≥1 EMA risk criterion and 29% had already received ≥3 prior bDMARDs classes.

A very high proportion of patients, four-in-five, initiating JAKi in UK before 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 them had previously received ≥3 different bDMARDs classes, it’s likely that many of them would have suitable alternatives. These data highlight the enormous impact of the recent licensing updates for JAKi class.

Z. Tian: None. L. Kearsley-fleet: None. J. Galloway: Honoraria; Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Vifor. Grants/research support; Abbvie, Galapagos, GSK, Janssen, Pfizer. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.