Abstract

Background: JAK inhibitors (JAKi) represent the latest development in the tackle to treat multiple inflammatory conditions. There is limited real-world data on their use. In 2022, the EMA Pharmacovigilance committee suggested that JAKi should only be used if alternative therapies are not available in patients over 65 years, smokers or those with cardiovascular or cancer risk factors. Objectives: To describe the demographics, duration of therapy and adverse events profile of patients prescribed JAKi at a large tertiary centre. Methods: The rheumatology database was reviewed to identify patients with past or current prescriptions of JAKi (Tofacitinib, Baricitinib, Filgotinib, Upadacitinib). Baseline data including age, gender, smoking status, ethnicity, co-morbidities, cardiovascular risk factors, rheumatic diagnosis, concomitant csDMARD use and prior biological therapies was collected. The duration of therapy on JAKi and reasons for stopping JAKi were identified. A Cox proportional hazard model was used to plot survival of drug therapy, by JAKi drug. Results: In total, 237 patients were prescribed a JAKi since 2017. The average age was 56.5, with a female predominance (n=195, 82%), and the majority had rheumatoid arthritis (Table 1). Baricitinib and Filgotinib represented the most commonly prescribed JAKi. About 16% of the cohort were using JAKi monotherapy (n=38). In those on combination therapy, methotrexate was the most commonly prescribed csDMARDs (n=82, 35%). Over 43% of patients had more than 1 prior biologic, with TNFi the most frequent (n=154, 65%). There were differences in the number of individuals with a cardiovascular risk factor, prior VTE and cancer diagnosis, between the four drug groups. The median duration of JAKi therapy was 2.3 years (IQR 1.0-3.9), with the lowest median duration seen with baricitinib (1.4, 0.9-3.7). One-third (n=79) of patients stopped JAKi therapy due to adverse events (n=35), primary failure (n=19) and secondary failure (n=22). Stopping therapy was most common with tofacitinib (n=27,52%). Drug survival was best on filigotinib (Figure 1). Patients who stopped JAKi therapy had a higher baseline DAS score compared to those continuing therapy (5.9 (5.4, 6.2) versus 5.5 (5.1-6.1), p=0.037). There were 5 new diagnoses of cancer whilst on JAKi therapy, of which 3 occurred whilst taking tofacitinib. There were 5 VTEs, of which 3 occurred on tofacitinib. Conclusion: One-third of individuals on JAKi therapy stopped treatment, with adverse events being the primary cause. Drug survival was best with filgotinib, although this drug has been licenced for a shorter duration than first-generation JAKi (tofacitinib and baricitnib). Table 1. Baseline table REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Zijing Yang: None declared, Katie Bechman UCB and viforpharma, Deepak Nagra: None declared, Benjamin Zuckerman: None declared, Maryam A. Adas: None declared, Mark Russell Lilly, Menarini, Galapagos, Mark Gibson: None declared, Ioasaf Karafotias: None declared, Edward Alveyn: None declared, Samir Patel: None declared, James Galloway AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB, AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.