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

OBJECTIVES: To 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. METHODS: TB 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. RESULTS: 96 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. CONCLUSION: Reactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.

A prospective study of anti-tumor necrosis factor therapy in South African rheumatoid arthritis patients.

OBJECTIVE: To quantify primary and secondary anti-tumour necrosis factor inadequate response (aTNF-IR) and intolerance in South Africans with rheumatoid arthritis (RA) over 1 year. METHODS: Rheumatologists from nine independent private practices monitored RA patients commencing on aTNF therapy (incident cases) or already on aTNF therapy (prevalent cases). Observations at baseline and quarterly intervals recorded discontinuation of therapy for either lack of response or adverse effects. RESULTS: Of the 98 patients screened, 86 were eligible to participate. Mean time from onset of symptoms of RA to start of aTNF treatment was 9.7 years (range: 0.5-32 years). Only 58 (67.4%) continued on aTNF therapy at 12 months, including five judged to have an aTNF-IR. Overall 12 patients had a secondary aTNF-IR with seven discontinuing for this reason. Seven patients discontinued due to adverse events, four due to funding problems and 10 were lost to follow-up. Infections were the most common adverse events, but only two stopped treatment as a result. No cases of active tuberculosis (TB) were recorded, despite nine patients having a positive tuberculin skin test and one, a past history of pulmonary TB. CONCLUSIONS: Almost a third of patients discontinued aTNF therapy over the 1-year period, with infections and inadequate response to treatment being the main reasons for discontinuation. The study highlights the need for biologics with alternative modes of action for patients with moderate to severe RA in South Africa.

South African recommendations for the management of rheumatoid arthritis: an algorithm for the standard of care in 2013.

Updated treatment recommendations for the therapy of rheumatoid arthritis (RA) in South Africa advocate early diagnosis, prompt initiation of disease-modifying anti-rheumatic drugs (DMARDs), and an intense treatment strategy where disease activity is assessed with a composite score such as the Simplified Disease Activity Index (SDAI). Frequent assessments and escalation of therapy are necessary until low disease activity (LDA) (SDAI ≤11) or ideally remission (SDAI ≤3.3) is achieved. Synthetic DMARDs may be used as monotherapy or in combination, and can be co-prescribed with low-dose corticosteroids if necessary. Biologic DMARD therapy should be considered for patients who have failed a 6-month trial of at least 3 synthetic DMARDs. All RA patients in SA are at increased risk of tuberculosis (TB), in particular patients using anti-tumour necrosis factor (TNF) biologic therapy. These recommendations provide practical suggestions for the screening and management of TB and other comorbidities, and offer an approach to monitoring of RA patients.

Suboptimal management of rheumatoid arthritis in the Middle East and Africa: could the EULAR recommendations be the start of a solution?

Although the prevalence of RA in the Middle East and Africa is comparable with that in other parts of the world, evidence indicates that its management in this region is suboptimal for a variety of reasons, including misconceptions and misunderstandings about the disease's prevalence and severity in the region, compounded by the lack of local epidemiological and health-economic data around the disease; the perception that RA is a low priority compared with other more prevalent conditions; delayed diagnosis, referral and treatment; and a lack of a region-specific, evidence-based management approach. In the absence of such an approach, the EULAR treatment recommendations may provide a useful starting point for the creation of guidelines to suit local circumstances. However, although agreement with the EULAR recommendations is high, many barriers prevent their implementation in clinical practise, including lack of timely referral to rheumatologists; suboptimal use of synthetic DMARDs; poor access to biologics; lack of awareness of the burden of RA among healthcare professionals, patients and payers; and lack of appropriate staffing levels.To optimise the management of RA in the Middle East and Africa, will require a multi-pronged approach from a diverse group of stakeholders-including local, national and regional societies, such as the African League of Associations in Rheumatology and International League of Associations for Rheumatology, and service providers-to collect data on the epidemiology and burden of the disease; to increase awareness of RA and its burden among healthcare professionals, payers and patients through various educational programmes; to encourage early referral and optimise use of DMARDs by promoting the EULAR treatment recommendations; to encourage the development of locally applicable guidelines based on the EULAR treatment recommendations; and to facilitate access to drugs and the healthcare professionals who can prescribe and monitor them.