POS0118 A WORLDWIDE PHARMACOEPIDEMIOLOGICAL UPDATE OF DRUG-ASSOCIATED ANCA-ASSOCIATED VASCULITIS AT THE TIME OF TARGETED THERAPIES
Authors: S. Deshayes, C. Dolladille, A. Dumont, N. M. Silva, B. Chretien, H. De Boysson, J. Alexandre, A. Aouba
Journal: Annals of the Rheumatic Diseases (2021)

Background: Several pharmacological classes are involved in drug-associated anti-neutrophil cytoplasmic antibody-associated vasculitis (DA-AAV). However, the literature data supporting the role a drug in the onset of DA-AAVs mainly rely on case reports or short series and implicate old treatments. Moreover, the advent of new treatments, including targeted therapies, may have modified the epidemiology of these adverse drug reactions (ADRs). Objectives: To update this list by using a pharmacovigilance-based data mining approach. Methods: We collected data on ADRs reported with the MedDRA preferred term “Anti-neutrophil cytoplasmic antibody positive vasculitis” up to November 2020, from the World Health Organization pharmacovigilance database. For each retrieved drug, a case/noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC025 value, which is the lower end of the 95% credibility interval, was considered significant. Results: A total of 483 deduplicated individual case safety reports of DA-AAV involving 15 drugs with an IC025&gt;0 were retrieved. DA-AAV occurred in 264 (71.2%, n=371) women, the median age at onset was 62 years [45-72], and the median time to onset between the introduction of the suspected drug and DA-AAV was 9 months [1-36]. DA-AAV occurrence was considered serious in 472 (97.7%, n=481) cases and fatal in 43 (8.9%) cases. The drugs associated with the highest disproportionate reporting were hydralazine, propylthiouracil, thiamazole, sofosbuvir, minocycline, carbimazole, mirabegron, and nintedanib (Table 1). Table 1. List of the 15 drugs associated with ANCA-associated vasculitis in the World Health Organization pharmacovigilance database with significant disproportional reporting, sorted by decreasing IC 025 . Drug N observed N fatal (%) IC 025 / IC ROR [95%CI] Delay (in days) between the introduction of the drug and AAV, median [Q1-Q3] (n available) Hydralazine 208 19 (9%) 8.2 / 8.4 2683.5 [2269.3-3173.3] 1277 (n=1) Propylthiouracil 108 4 (4%) 7.2 / 7.5 1201.5 [974.8-1480.9] 1003 [425-1959] (n=19) Thiamazole 40 5 (13%) 5.2 / 5.6 138.7 [100.7-191.1] 411 [58-966] (n=6) Sofosbuvir 46 0 4.9 / 5.3 74.6 [55.3-100.8] (n=0) Minocycline 17 0 3.8 / 4.6 72.4 [44.7-117.3] (n=0) Carbimazole 6 0 2.0 / 3.4 44.9 [20.1-100.4] 92 (n=1) Mirabegron 7 2 (29%) 1.5 / 2.7 11.1 [5.3-23.3] 291 [289-415] (n=3) Nintedanib 6 2 (33%) 1.4 / 2.8 14.2 [6.3-31.7] 56 [36-132] (n=4) Penicillamine 4 1 (25%) 1.4 / 3.1 170.3 [63.5-456.3] (n=0) Influenza vaccine 29 2 (7%) 1.3 / 1.9 4.1 [2.8-6.0] 24 [20-26] (n=7) Allopurinol 7 2 (29%) 1.2 / 2.4 8.0 [3.8-16.8] (n=0) Rifampicin 7 2 (29%) 0.6 / 1.9 4.7 [2.2-9.8] (n=0) Peginterferon alfa-2b 4 0 0.3 / 2.1 7.0 [2.6-18.6] 98 (n=1) Montelukast 4 4 (100%) 0.2 / 1.9 5.8 [2.2-15.5] (n=0) Rosuvastatin 6 0 0.1 / 1.5 3.4 [1.5-7.5] (n=0) IC: information component; ROR: reporting odds ratio; CI: confidence interval; AAV: ANCA-associated vasculitis Conclusion: This study strengthens the previously suspected association but also identifies 3 new drugs that may cause DA-AAV. Particular attention should be given to these drugs by prescribers and in experimental studies. Disclosure of Interests: None declared