AB0989 TUBERCULOSIS RISK IN CHILDREN WITH RHEUMATIC DISEASES TREATED WITH BIOLOGIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS

Abstract

Background:Chronic rheumatic diseases entail the use of biologics in children. Immunosuppressive effects of drug therapy put children at risk of various infections. Tuberculosis (TB) is a leading chronic infection in certain parts of the world. Recent estimates suggest the prevalence of TB in India to be 3.2 cases per thousand population1.Objectives:Thus we reviewed the prevalence of Tuberculosis amongst children with various rheumatic disorders treated with different biologics.Methods:The search strategy for writing review articles proposed by Gasparyan et al2. was followed. Articles available on MEDLINE and Scopus, published on or after January 1, 2010 to 1 October 2019, were reviewed. (Figure 1) Details on Tuberculoisis and disease variables were collected (Table 1).Table 1.Data extraction formData extraction formDrugStudy characteristics Country of study Type of study Year Author DOIOutcomes reported Number of participants Total number of Tuberculosis reportedDisease variable Disease or type of JIA (PA-RF+, PA-RF-, OA, OA extended, ERA, jspA, SJIA, PsA, Undifferentiated, only uveitis) Duration of JIA before biologics (Median, IQR) Duration of follow-up (Median) Exposure in patient yearsInfectious events Total no of infection events Major/ serious Infections- Number of events Opportunistic infections Minor Infections- Number of eventsTreatment received Biologic Doses received Duration of biologic treatment Concomitant drugs Steroids OtherFigure 1.Number of articles obtained after searching through MEDLIEN and Scopus.Results:Data on infections in children with rheumatic disorders on biologics is scant (Table 2, Figure 2A). Tuberculosis was reported on occasion (0-5 cases per country) in the developed world with the highest Tuberculosis reports being from Turkey (Figure 2B). There is particular paucity of data from regions with highest number of incident cases or prevalence of tuberculosis more than 100 per 10 000 population (figure 2C, D).Table 2.Summary of data on tuberculosis in paediatric rheumatology with various biologicsJIALupusMyositisAutoinflammatory syndromesVasculitisInfliximab783(A)547(B)00010(C)9(B)Adalimumab2925 (A)489(B)0001(B)11(C)Etanercept6974 (A)2019(B)0001(C)Certolizumab37 (A)0(B)0000Golimumab224 (A) 3(B)0000Rituximab107 (A) 51(B)75(B)48(E) 185(C)03(C)Belimumab0(A) 0(B)39(B)000Anakinra471 (A) 63(B)0029(A) 27(B)1(D)0Canakinumab196 (A)004(A)109(E)0Tocilizumab998 (A)0002 (B) 9(C)Abatacept521 (A)0000Combination of anti TNFs3(A)0000A: Registry data, B: Cohort, C: Case series, D: Anecdotal reports E. TrialsFigure 2A. Data available on children with pediatric rheumatic disorders on biologics B. Number of Tuberculosis cases reported from studies summarized in figure 2A C. Number of cases worldwide*D. Global incidence of Tuberculosis per 10000 people#Retrospective studies of duration 10 m- 10years suggest that TB risk is minimal in pediatric rheumatology patients on biologics in low TB incident areas. However, most prospective studies suffer from short observation period (Table 2). Most registries focus on response to therapy rather than complications.Conclusion:TB risk is minimal with biologics use in peadiatric rheumatology in areas with low TB incidence (<99 cases per 10 000 population). However, most prospective studies are hampered by short observation period. There is insufficient data to establish safety in countries with high background prevalence of TB. Long term prospective national registries are needed from in TB countries with focus on risk factors for infections.