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

By on November 13, 2015

Cape Arthritis and Rheumatology



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.


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.


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.


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.

Key words:

anti-TNF agents, drug survival, rheumatoid arthritis, South Africa.

Introduction to Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease which if inadequately treated, leads to progressive joint destruction.1–4 In South Africa, patients in the private sector who have an inadequate response to traditional disease-modifying anti-rheumatic drugs (DMARDS), have for more than a decade had limited access to biologic agents, principally the anti-tumor necrosis factor (aTNF) drugs (infliximab, etanercept and adalimumab). Guidance on their use has been determined by the South African Rheumatism and Arthritis Association (SARAA) and these agents, usually in combination with methotrexate, have become established as the standard of care for those unresponsive to DMARDS (DMARDS-IR). However, not all patients with RA respond to aTNFs and about 30% fail to achieve an American College of Rheumatology (ACR)- 20 response (primary failure) in large randomized controlled trials.1–3 In addition, there may be further drug attrition either because of secondary failure or adverse events, including infections such as tuberculosis (TB).5,6 South Africa is a TB endemic country with the 2010 World Health Organization (WHO) report showing a prevalence rate of 798/100 000, one of the highest rates in the world.7,8 In spite of screening and chemoprophylaxis for active and latent TB infection (LTBI) prior to commencement of aTNF therapy, reactivation of TB continues to be a challenge.

The recent availability of other biological agents with different molecular targets, such as rituximab, tocilizumab and abatacept, provide alternatives for patients who fail aTNFs or have adverse events. In the absence of any post-registration data on aTNF agents in SA, a prospective observational study was undertaken to assess the effectiveness and tolerability of these agents in the private sector.

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Dr Clive Pettipher is a leading expert in the field of Arthritis and Rheumatology and established Cape Arthritis and Rheumatology in 2015 in the iconic Busamed Hospital.

He qualified as a specialist physician in Johannesburg in 1998 and rheumatologist in 2000. He completed his fellowship at Chris Hani Baragwanath Hospital, acquiring invaluable training.

He started a private practice at Wilgeheuwel Hospital in 2001 until 2014 in rheumatology. He ran a large biologics clinic with over 200 patients on these life changing therapies. His ongoing special interests include the following
• research in biological therapies in South Africa and currently manages the South African Biologics Registry (SABIO).
• Musculoskeletal imaging - ultrasound of tendons and joints related to rheumatology - trained overseas by the European League Against Rheumatism.

He is honored to be a recent president of the South African Rheumatism and Arthritis Association (SARAA) during which time he published the South African Recommendations for the Management of Rheumatoid Arthritis: 'An algorithm for the standard of care in 2013', SAMJ.

He has also published various articles on tuberculosis in international journals and was awarded the Solly Herwitz academic prize for his research and the best MMed in 2000 at the University of the Witwatersrand. He is currently an advisory board member for Roche, Abbvie and Jansen Pharmaceuticals.