Tuberculosis in biologic users for rheumatic diseases: results from the South African Biologics Registry (SABIO)

Abstract

ObjectivesTo evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome.MethodsTB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical companies. Demographics, LTBI screening and treatment, biological and disease modifying antirheumatic drug (DMARD) therapies, TB diagnosis and outcomes were recorded.Results96 TB cases were collected from 1999 to June 2017: rheumatoid arthritis 55, ankylosing spondylitis 27, psoriatic arthritis 4, and juvenile inflammatory arthritis 10. The TB rate was 1240/100 000 person years for biologic users (n=96) versus the biologic naive cohort of 0/100 000 years with an incidence rate difference of 0.0124 (p<0.0001). 60/96 had pulmonary and 36/96 had extra-pulmonary TB. Reactivation TB occurred in 45/96 cases. TB occurred in all biologics licenced in South Africa, the majority in monoclonal inhibitors (1683/100 000 person years) compared with etanercept (861/100 000 person years) and non-tumour necrosis factor (TNF) inhibitors (681/100 000 person years). The incidence rate ratio for monoclonal inhibitors compared with etanercept was 1.96 (p=0.005) and 2.47 (p=0.002) compared with non-TNF inhibitors with no significant difference between non-TNF inhibitors and etanercept (p=0.336). From those (12.9%) who screened LTBI positive, 14 developed TB, while the majority (77) screened LTBI negative. Black race, male sex, younger age and residence in the Western Cape were statistical risk factors. Two drug resistant TB cases and six deaths occurred.ConclusionReactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.

Infections in Patients with Rheumatoid Arthritis in the Era of Targeted Synthetic Therapies

“…The introduction of TNFi in clinical practice led to a significant increase in cases of tuberculosis (TB) reactivation in patients with an undiagnosed, underlying latent TB infection (LTBI). 38 Although TB reactivation was mainly associated with TNFi, TB cases have been reported at a lower rate with other bDMARDs 39 , 40 and tsDMARDs. 22 However, the universal screening of patients prior to bDMARD initiation with the tuberculin skin test (TST) and/or the newer Interferon Gamma Release Assays (IGRAs), have led to a substantial decrease of newly diagnosed TB cases (∼80%).…”

“…Despite appropriate baseline screening, cases of TB continue to be diagnosed worldwide during long term b- or ts-DMARD therapy. 39 , 40 These cases are thought to be mainly due to TB re-exposure rather than reactivation. In the long-term extension studies of RCTs in RA patients treated with TNFi, 48 non-TNFi 49 bDMARDs or ts-DMARDs 22 , the incidence rate of TB ranged between 0.1 to 0.2/100 patient-years.…”

“…For example, in the UK, the incidence rate of TB in 2015 was 0.04/100 patient-years 39 whereas in South Africa the respective rate was much higher at 1.2/100 patient-years. 40 …”

Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018

“…We estimated the incidence of TB disease in public health sector patients exposed to biologic therapies in South Africa, Western Cape. We found that the estimated incidence rate among biologic therapy users was higher compared to previously published literature [22,24]. When comparing estimated tuberculosis disease incidence rates to the estimated background incidence rate of 681 cases per 100,000 per year in the Western Cape [25], the estimated risk of tuberculosis disease is 3.3 fold higher overall, and is 4.1-fold and 2.7-fold higher than background incidence rates in TNF-α and non-TNF-α biologic therapies respectively.…”

“…The South African Biologics Registry (SABIO) captures biologic use data for South African patients receiving private health care, but these are generally individuals with higher socio-economic circumstances and lower risk of exposure to TB, and are not representative of the general South African patient population. When comparing the TB incidence rates in TNF-α inhibitors users in the SABIO registry, incidence was 1387 per 100,000 person-years, which is approximately 10-fold that of the British (BSRBR), French (RATIO) and Spanish (BIOBADASER) registries where the TB incidence ranges from 106 to 172 per 100,000 person-years [22,24].…”