OA39 The influence of safety warnings on the prescribing of JAK inhibitors in England: an interrupted time-series analysis
Authors: Russell Mark D , Yang Zijing , Walter Ben , Alveyn Edward , Bechman Katie , Miracle Aitana , Nagra Deepak , Adas Maryam A , Galloway James B 
Published: April 2024

Abstract

Background/Aims
JAK inhibitors (JAKi) were launched in the UK for rheumatoid arthritis in 2017. Licenced indications have subsequently expanded to include other inflammatory arthritides, inflammatory bowel disease, psoriasis and atopic dermatitis. Since then, there have been numerous safety warnings from regulatory bodies, with signals for cancer, venous thromboembolism and cardiovascular events. We set out to compare how these safety warnings have influenced prescribing behaviour for individual JAKi medications in England.

Methods
We analysed aggregate prescribing data from all NHS hospitals in England between January 2019 and July 2023. We compared monthly prescriptions issued for individual JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib) across all licenced indications. Standardisation was performed using WHO Daily Defined Doses. We conducted interrupted time-series analyses to evaluate whether changes in prescribing behaviour occurred after: i) the initial press release for the ORAL Surveillance trial data (January 2021); and ii) the European Medicines Agency (EMA) safety committee warning for the JAKi class as a whole (October 2022).

Results
Overall, JAKi prescribing has increased year-on-year since 2019; however, striking differences exist for individual JAKi medications. Pre-2021, an estimated additional 93 patients per month were newly initiated on tofacitinib. After the ORAL Surveillance press release (January 2021), tofacitinib initiations decreased to 26 new patients/month (p &lt; 0.001). Following the EMA safety warning (October 2022), tofacitinib prescribing fell sharply (71 fewer patients/month; p &lt; 0.001). A similar pattern was observed for baricitinib - pre-2021: 145 new patients/month; post-Jan 2021: 15 new patients/month; post-Oct 2022: 60 fewer patients/month (all, p &lt; 0.001). In contrast, prescriptions for the JAK1-selective inhibitors (upadacitinib and filgotinib) have increased markedly since 2021, with no apparent impact of the pan-JAKi safety warnings. In July 2023, baricitinib remained the most prescribed JAKi in England across all indications (175,245 defined daily doses [DDD]) followed by upadacitinib (154,510 DDD), tofacitinib (105,215 DDD), and filgotinib (72,445 DDD).

Conclusion
Prescribing of JAKi has changed markedly in association with emerging safety warnings, with significant reductions in prescriptions for tofacitinib and baricitinib. It is notable that warnings have emerged for the JAKi class as a whole, yet prescriptions for the JAK1-selective inhibitors, upadacitinib and filgotinib, have continued to increase. Explanations could include clinicians' interpretation of risk differences within the JAKi class, as well as external pressures such as price and licenced indications.

Disclosure
M.D. Russell: Honoraria; AbbVie, Biogen, Eli Lilly, Galapagos, Menarini. Grants/research support; Eli Lilly, Janssen, Pfizer, UCB. Z. Yang: None. B. Walter: None. E. Alveyn: None. K. Bechman: Grants/research support; Versus Arthritis/Pfizer. A. Miracle: None. D. Nagra: None. M.A. Adas: None. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.