AB0382 COMPARISON OF ADVERSE EVENTS (AEs) RELATED TO MAJOR ANTI-RHEUMATIC DRUGS, REPORTED TO THE OFFICIAL JAPANESE ADVERSE DRUG EVENT REPORT DATABASE (JADER)

Abstract

BackgroundCurrently, many disease-modifying anti-rheumatic drugs (DMARDs) are available for the treatment of rheumatoid arthritis (RA). Among them, methotrexate (MTX), biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) are the major options. AEs related to these are major concerns. In Japan, the AEs data spontaneously reported to and summarized by Pharmaceuticals and Medical Devices Agency (PMDA) are freely accessible.ObjectivesThe major AEs relating to MTX, bDMARDs, and JAKi observed in the real world were compared.MethodsThe number of AEs listed by JADER from 2014 to 2020 was collected. The AEs were classified by System Organ Class (SOC) of Medical Dictionary for Regulatory Activities (MedDRA) and compared using the chi-square test. The bDMARDs included were etanercept (ETN), adalimumab (ADA), golimumab (GOL), tocilizumab (TCZ), and abatacept (ABT), and JAKi was tofacitinib (TOF) and baricitinib (BAR).ResultsThe total number of AEs was 27,604. The number was significantly increasing in total and MTX, GOL, TOF during these years, although the number of cases that have each DMARD is not known in this study. The proportion of SOCs among each DMARD was similar throughout the period.The most frequent was infections/infestations in all DMARDs except for MTX, in which neoplasms were the most. The primary cause of infection was bacterial, including pneumonia. Varicella-zoster virus infection in JAKi, and tuberculosis in ADA and GOL were conspicuous.Neoplasms were the second major in many DMARDs. Lymphoproliferative disorders were most common in MTX-related neoplasms, whereas solid tumors were more in other DMARDs like ABT or BAR.Other SOCs include all other categories such as the musculoskeletal, nervous system, cardiac, and vascular disorders. Among them, major adverse cardiovascular events (MACE, including cardiovascular death, myocardial infarction and stroke) and venous thromboembolism (VTE) were both reported in small numbers. However, more MACE was noted in BAR and GOL, and more VTE was in BAR and TOF compared to other DMARDs.ConclusionThe number of AEs cases related to DMARDs was increasing. Significant difference among AEs related to DMARDs was noted in the JADER database, especially regarding MTX and JAKi.References[1]S. Inokuma. Expert Open Drug Saf. 2021 Nov 11. Online ahead of print.Table 1.Total case numbers and proportion of adverse events related to each DMARD.DMARDs (year of launch)TotalMTX (1999)ETN (2005)ADA (2008)GOL (2011)TCZ (2008)ABT (2010)TOF (2013)BAR (2017)Number of AEs2760411636297419591302424517093065714Blood/lymphatic system disorders5.89.92.03.22.64.00.92.83.5Gastrointestinal disorders5.04.13.47.55.97.73.95.24.2General disorders/administration site reactions4.63.211.34.12.23.04.07.62.5Infections/infestations28.020.321.332.234.236.537.137.049.2 Pneumonia (bacterial)6.64.06.15.210.97.712.59.415.1 Other bacterial infection9.15.95.612.39.517.69.19.810.6 Herpes zoster2.11.10.41.41.21.01.28.211.2 Tuberculosis1.40.91.96.03.50.60.60.31.0Investigations5.04.95.52.32.65.72.28.32.8Neoplasms benign, malignant, unspecified21.134.811.013.512.77.415.610.815.4 Lymphoproliferative diseases14.329.82.84.14.02.24.52.12.2 Solid tumors5.63.87.37.87.54.09.97.310.5Respiratory, thoracic, mediastinal disorders7.16.88.38.49.56.57.46.26.7Other System Organ Class23.315.937.328.830.229.228.922.215.7 Major adverse cardiovascular events1.10.41.11.62.51.51.61.32.9 Venous thromboembolism0.40.10.40.50.60.30.21.11.4Background colors indicate: comparing to the total cases, higher with p<0.05, light pink; higher with p<0.00001, dark pink; higher with p<1E-10, red. Lower with p<0.05, light blue; lower with p<0.00001, blue; lower with p<1E-10, dark blue, using chi-square test. Yellow indicates System Organ Classes.Figure 1.Total number of adverse events reported from 2014 to 2020.Linear regression is shown only for DMARDs with increasing numbers of AEs.Disclosure of InterestsNone declared