Journal Article

AB0460 JAK INHIBITOR DISCONTINUATION RATES: RETROSPECTIVE REAL-WORLD DATA FROM A TERTIARY CENTRE

Jubber, A., Ganguly, S., Moorthy, A., Bland, K.

2023

Overview

BackgroundJAK inhibitor uptake has increased in recent years, and recent NICE (National Institute for Health and Care Excellence) approval of certain JAK inhibitors for moderate rheumatoid arthritis disease activity will likely increase this further. The EULAR guidance on the management of rheumatoid arthritis recommends JAK inhibitors as part of the treat-to-target strategy, provided certain risk factors are considered [1]. However, there remains limited data on discontinuation rates for this drug class.ObjectivesThis retrospective study aimed to measure the discontinuation rates of the four UK approved JAK inhibitors in a multi-ethnic population at a UK tertiary centre, thereby providing real-world data on the durability of the different JAK inhibitors.MethodsAll patients ever prescribed a JAK inhibitor at University Hospitals of Leicester were identified on a drug monitoring database. Discontinuation rates were calculated for each JAK inhibitor, as well as the median duration of time on each drug prior to discontinuation. The baseline characteristics of the patients who discontinued a JAK inhibitor were documented, as well as reason for discontinuation. These were categorized as either primary inefficacy, secondary inefficacy, toxic adverse events, non-toxic reasons, and disease remission.ResultsIn total, 375 patients had been prescribed a JAK inhibitor since 2018. Discontinuation rates and duration of time prior to discontinuation for each drug are shown in Table 1.Table 1.JAK inhibitor discontinuation rates and duration of use.Duration prior to discontinuation (weeks)DrugNumber of patientsProportion discontinuedMedianMinimumQ1Q3MaximumMeanStandard deviationStandard error of meanBaricitinib23351/233 (21.89%)35.000.8618.4368.14230.1049.5548.686.82Tofacitinib6133/61 (54.09%)70.295.2937.8696.93161.1072.3543.297.54Filgotinib514/51 (7.84%)13.504.716.5415.8616.1411.965.142.57Upadacitinib300/30 (0%)n/an/an/an/an/an/an/an/aFigure 1.JAK inhibitor survival proportions.Of the 88 patients who discontinued a JAK inhibitor, 86% were female and 14% male. Median age was 60 years (IQR 53-70 years), and median duration of drug intake was 45.60 weeks (IQR 19.29-74.07). Of these 88 patients, 77% were Caucasian, 20% from the Indian subcontinent, and the remaining patients mixed race, Asian other, and not stated. Furthermore, 65.9% of patients were on concomitant DMARDs, 71.6% had received a previous biologic drug (median number of previous biologics was 1 [0-2]). Diagnosis was seropositive RA (rheumatoid arthritis) in 59.1%, seronegative RA in 27.3%, PsA (psoriatic arthritis) in 11.4%, and 2.2% in RA/PsA overlap.Of the 88 patients where the JAK inhibitor was discontinued, reasons included primary inefficacy 37.5%, toxic adverse events 35.23%, non-toxic reasons 17.05%, secondary inefficacy 5.68%, disease remission 1.14%, and not stated 3.41%. Adverse events of interest included viral infections 6.81%, non-viral infections 4.54%, malignancy 2.27%, and MHRA alerts 9.09%. In this multi-ethnic population, there were no discontinuations for venous thromboembolism, or major adverse cardiovascular events, although patients are screened for risk factors prior to commencement, and MHRA alerts led to discontinuation if risk factors developed during treatment.ConclusionIn this real-world population, tofacitinib followed by baricitinib had the highest discontinuation rates. While discontinuation rates for the 2nd generation JAK inhibitors appear more promising, patient numbers were lower. The most common reasons for discontinuation were primary inefficacy and toxic adverse events. Further real-world observational data is needed, particularly from multi-ethnic patient populations, to increase confidence levels in JAK inhibitor prescribing.Reference[1]Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):3-18.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Adverse events / Inflammatory arthritides / Malignancy / Minority & ethnic groups / Patients / Psoriatic arthritis / Real-world evidence / Remission / Remission (Medicine) / Rheumatoid arthritis / Risk factors / Scientific Abstracts / Targeted synthetic drugs / Thromboembolism / Viral infections