Background Biological therapy, especially anti-tumor necrosis factor alpha, increases the risk of reactivation of latent tuberculosis (TB) infection in patients with rheumatoid arthritis (RA) (1). The influence of the underlying RA itself and the effects of different traditional DMARD therapies on the risk for TB is still unclear in those not receiving biological therapy. In South Africa, the TB prevalence rates are very high (2).
Objectives We investigated the risk of TB in patients with RA without previous exposure to biological therapy and managed with traditional DMARD therapies.
Methods A retrospective cohort study of patients with RA seen at the Groote Schuur Hospital Arthritis Clinic during 1985-2014 was done. All patients were biologic therapy-naïve. We estimated the TB risk related to individual DMARD therapies that included chloroquine (CQ), methotrexate (MTX), sulphasalazine (SSZ) and prednisone (PRED).
Results There were 638 patients, mean follow-up of 7.2 years, mean age at diagnosis of 49.3 years and 82.3% were female. 49 patients (7.7%) had been treated for TB prior to the diagnosis of RA. During follow-up, 17 patients (2.7%) developed TB, mean time to TB diagnosis was 3.1 years. The most frequently used DMARD combinations were MTX, PRED with CQ (30.4%), MTX, PRED, CQ with SSZ (14.3%) and MTX with PRED (12.9%). During 4620 person-years of follow-up, the incidence rate of TB was 367.9/100.000 (95%CI 229-592). The incidence rate of active TB decreased with an increase in the MTX and CQ doses, but increased with an increase in the PRED dose as well as with the use of DMARD combinations that contained PRED (see Table). A history of previous TB was not associated with an increased risk of TB.
Conclusions Previous TB in our population of RA patients was not uncommon, but this was not associated with an increased risk of developing TB after the diagnosis of RA. The incidence rate of active TB was not higher than that reported in the general population in South Africa. A higher dose of MTX and CQ was associated with lower risk and a higher prednisone dose with a higher risk of developing TB on DMARD therapy. Our results underline the need to also screen for latent and active TB in RA patients being considered for non-biologic DMARD therapies if medium to high dose prednisone is used.
Souto A, et al. Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies. Rheumatol Oxf Engl. 2014 Oct;53(10):1872–85.
Murray CJL, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014 Sep 13;384(9947):1005–70.
Disclosure of Interest None declared