POS0545 Retrospective analysis of cardiovascular and malignancy risk factors in real world JAK inhibitor cohort and the effects of UK regulatory agency guidance cautioning JAK inhibitor use on prescribing
Year: 2025
Type: conference-abstract
Abstract: Background: Janus kinase inhibitors (JAKi) are licensed for the treatment of inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Clinical trial evidence, notably from the ORAL surveillance trial of tofacitinib [1], suggested an increased risk of major cardiovascular adverse events (MACE), malignancy and venous thromboembolism (VTE) in RA patients aged 50 or older with at least one additional cardiovascular risk factor, when treated with JAKi, compared to matched patients treated with TNF inhibitors. In a post-hoc analysis of the ORAL surveillance, high risk of events was associated with smoking and age over 65. In April 2023 the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued guidance cautioning the use of JAKi in patients with cardiovascular or malignancy risk factors when other treatment options are available for use [2]. Objectives: To evaluate the numbers of MACE, VTE and malignancy cases in a real-world population of JAKi exposed patients. To assess the effect of MHRA guidance on JAKi prescribing rates and the treatment of patients with cardiovascular risk factors already receiving JAK in a tertiary referral centre. Methods: Following the MHRA guidance the electronic records of all patients started on JAKi at Leeds Teaching Hospitals NHS Trust (LTHT) between November 2014 (when tofacitinib became available on a compassionated access scheme) and December 2023 were reviewed. Past medical history of cardiovascular disease, malignancy and VTE, as well as relevant risk factors and new cases were recorded. The reason for JAKi withdrawal at any time was recorded. Results: Two-hundred and fifty patients were actively taking JAKi and a total of 458 JAKi exposures were identified in LTHT rheumatology department for all indications. Thirty-two patients had 2 or more JAKi exposures. At JAKi initiation mean age was 54 years (range 16-82), 56 patients (22%) were >65 years. Of the 250 patients at LTHT currently taking a JAKi, 138 (55%) had risk factors for MACE and 73 (29%) had 2 or more risk factors at baseline. Eight patients with risk factors started JAKi post MHRA guidance, none of whom were older than 65 or active smokers. Twenty-two (of 250) (9%) patients had previously tried all other classes of targeted therapy prior to JAKi. An additional 4 (2%) in whom TNFis had been deemed contra-indicated, had tried the other 3 available classes. Of 33 (13%) patients on a JAKi as 1 st line therapy, only 1 started post April 2023. One patient in the cohort had a non-ST elevation myocardial infarction during follow up. Baricitinib was continued due to patient choice, with cardiology approval, because of significant improvement in RA activity. Twenty-nine had either a past history of malignancy or a known pre-malignant condition. Of the current cohort of JAKi patient, 236 (94.4%) were started on their JAK inhibitor before the MRHA warning on the use of JAK inhibitors in patients with cardiovascular disease or malignancy. In the 6 months prior to the MHRA guidance 44 patients started JAKi, in the 6 months following, 14 patients were initiated on therapy. In those who had withdrawn JAKi (n=208) the reasons for stopping were primary non-response (n=70), secondary loss of response (n=51), recurrent or severe infections (n=16), {including 1 case of tuberculosis}, gastrointestinal side effects (n=21), headaches (n=4), VTE (n=2), malignancy (n=5), liver/renal disfunction (n=5), death (n=3), other (n=24). In 7 patients, JAKi treatment was switched to an alternative due to pre-existing cardiovascular risk factors based on patient or clinician preference and 4 patients had the dose reduced. Conclusion: In a real-world population of 458 JAKi exposures, only 1 MACE case was observed, although 7 patients withdrew treatment due to perceived risk, 2 due to VTE and 5 due to the development of a malignancy. Most patients stopped treatment due to lack of efficacy. MHRA guidance does appear to have had an effect on use of JAKi with a reduction in prescribing in the 6 months post guidance and a reduction in the use of JAKis as a first line therapy. Few patients have stopped treatment due to concerns about risk factors. REFERENCES: [1] Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022;386(4):316-26. [2] Janus kinase (JAK) inhibitors: new measures to reduce risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality. In: Drug safety update. Volume 16. Issue 9 April 2023:2. Available at URL: https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality. Table 1Cardiovascular, malignancy or VTE risk factors in current JAKi cohort (n=250).YesNoNotdocumentedDeveloped post initiationSmoker62 (24.8%)129 (51.6%)59 (23.6%)0 (0%)Angina/ischemic heart disease10 (4%)231 (92.4%)7 (2.8%)2 (0.8%)Previous MI8 (3.2%)233 (93.2%)8 (3.2%)1 (0.4%)Cerebrovascular disease6 (2.4%)236 (94.4%)6 (2.4%)2 (0.8%)Diabetes20 (8%)222 (88.8%)7 (2.8%)1 (0.4%)Obesity31 (15.1%)166 (66.4%)50 (20%)3 (1.2%)Hypertension63 (25.2%)173 (69.2%)9 (2.4%)5 (2%)High lipids68 (27.2%)116 (46.4%)38 (15.2%)28 (11.2%)Prev/current malignancy17 (6.8%)220 (88%)9 (3.6%)4 (1.6%)Pre-malignant conditions13 (5.2%)196 (78.4%)41 (16.4%)0 (0%)VTE risk factors17 (6.8%)218 (87.2%)13 (5.2%)2 (0.8%)History of VTE5 (2%)236 (94.4%)7 (2.8%)2 (0.8%)OCP or HRT4 (1.6%)234 (93.6 %)9 (3.6%)3 (1.2%)Immobility2 (0.8%)241 (96.4%)3 (1.2%)4 (1.6%)(MI – myocardial infarction, VTE – venous thromboembolism, OCP – oral contraceptive pill, HRT – hormone replacement therapy). Acknowledgements: NIL . Disclosure of Interests: John Fitton Pfizer, Andrea Di Matteo: None declared, Lesley-Anne Bissell Abbvie, Alfasigma, Alfasigma, Jacqueline Nam: None declared, Kulveer Mankia Abbvie, ALLin Bio, Astra Zenica, UCB, Lilly, Galapagos, Seran Healthcare, Zura Bio, Deepcure, Gilead, Lilly, Serac Healthcare, AstraZeneca, Deepcure, Paul Emery Abbvie, Activa, Astra-Zenica, BMS, Boehringer Ingelheim, Galapagos, Gilead, Immunovant, Jansen, Lilley, Novartis, Abbvie, BMS, Lilly, Novartis, Pfizer, Samsung, Shouvik Dass Abbvie, Galapagos, Lilly, Benazir Saleem: None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.
Source: Annals of the Rheumatic Diseases
Institutions: Leeds Teaching Hospitals NHS Trust, University of Leeds
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,870
OpenAlex ID: W4411421108