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Background: In recent years, there has been a greater emphasis on the safety of JAK inhibitor (JAK-I) treatment in rheumatologic patients. In October 2022, the European Medicines Agency's (EMA) safety committee presented recommendations for preventative strategies to reduce adverse effects related with JAK-I treatment, including cardiovascular, thromboembolic, and neoplastic concerns. Objectives: The study aims to assess the impact of EMA guidelines on real-life prescribing practices in rheumatoid arthritis (RA) patients eligible for JAK-I treatment. The secondary objective is to assess the JAK-I safety profile by evaluating reasons for treatment discontinuation and monitoring adverse events, focusing on cardiovascular, thromboembolic, and neoplastic events. Methods: We conducted a single-centre observational retrospective study. The study included adult RA patients treated with a JAK-I for the first time between January 2018 and December 2023. Patients were divided into two groups based on the period when JAK-I started (before vs after October 2022). The following parameters were compared: demographic data, clinical characteristics, outcomes measures, and adverse events. To assess comorbidities and cardiovascular risk the Rheumatic Disease Comorbidity Index and the Expanded Risk Score in RA (ERS-RA) were calculated. Results: The study included 183 patients: 134 eligible for Baricitinib, 25 for Tofacitinib, 15 for Upadacitinib, and 9 for Filgotinib. In 2018, 49 patients started JAK-I therapy, followed by 46 in 2019, 22 in 2020, 33 in 2021, 28 in 2022, and 5 in 2023. JAK-I was prescribed in 175 patients before October 2022 and in 8 patients after October 2022. No significant differences were observed by comparing the two groups (Table 1). Among 183 patients, 112 (60%) discontinued JAK-I therapy: 58 due to primary/secondary inefficacy, 42 due to adverse events neoplasms (3), hepatopathy (5), venous/arterial vascular events (6), infectious events (18), others (10), 11 due to a new risk assessment, based on EMA recommendations, and 1 due to personal decision. Fifteen individuals (8%) had adverse cardiovascular, thromboembolic, or neoplastic events, which resulted in JAK-I discontinuation in 9 patients (5%). All these subjects commenced JAK-I before the EMA recommendations. The clinical-demographic characteristics of these patients are detailed in Table 2. All the subjects who experienced cardiovascular/thromboembolic adverse events (8/183, 4%) had at least one other concurrent cardiovascular risk factor and/or were above the age of 65. During therapy, 7 patients developed a neoplastic condition; however, only 3 required tsDMARD discontinuation due to invasive/malignant features. Conclusion: Our study found no significant change in patient characteristics before and after EMA recommendations, most likely due to a lack of statistical power. Despite the small sample size, our findings indicate that patients who started JAK-I after the EMA recommendations had lower cardiovascular, thromboembolic and neoplastic risk factors. However, both groups had a significant cardiovascular risk (ERS-RA>7.5%), which is presumably driven by disease activity at medication beginning. According to our observations, the number of RA patients commencing their first JAK-I appears to have decreased significantly following the publication of EMA recommendations. Furthermore, after reassessing risk factors, 10% of patients receiving JAK-I therapy at the time of EMA guideline release were advised to discontinue treatment to reduce risks. Adverse events, such as cardiovascular, thromboembolic, and neoplastic issues, do not appear to have increased considerably in our case series. All of these occurrences happened in patients who commenced JAK-I before EMA guidelines. This data suggests that rheumatologists have taken into account the EMA recommendations. These results need to be confirmed by further evidence. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Elda Piovani: None declared, Claudia Barison: None declared, Paola Bizioli: None declared, Roberta Martinelli: None declared, Chiara Bazzani AbbVie, Lilly, Novartis, Franco Franceschini Pfizer, Galapagos, AbbVie, Lilly, Pfizer.
Piovani et al. (Sat,) studied this question.