ArticlesGolimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial
Introduction
Development of drugs to target tumour necrosis factor α (TNFα) has been one of the most impressive advances for the treatment of inflammatory diseases, including rheumatoid arthritis, in the past decade. However, some patients do not tolerate or respond adequately to available TNFα inhibitors. Thus, increased use of TNFα inhibitors to manage rheumatoid arthritis is likely to be accompanied by increased occurrence of patients who have previously received TNFα inhibitors. Such patients are frequently treated with more than one TNFα inhibitor, according to observational studies and registries.1, 2, 3, 4 However, no prospective, controlled clinical trial has been done to establish whether patients who discontinued treatment with one TNFα inhibitor would respond to treatment with another TNFα inhibitor. The decision to treat with an alternative TNXα inhibitor is based on retrospective analyses of registry data or non-blinded observational studies with small numbers of patients.1, 2, 3, 4, 5 By contrast, the efficacy of other biologically derived drugs, such as the B-cell depleting chimeric antibody rituximab or the T-cell co-stimulation inhibitor abatacept, have been assessed in well designed, controlled studies of patients who did not respond to a TNFα inhibitor.6, 7
Three TNFα inhibitors are licensed to treat rheumatoid arthritis: adalimumab, a human monoclonal antibody that is given subcutaneously every 2 weeks; etanercept, a TNF-receptor fusion protein that is given subcutaneously once or twice per week; and infliximab, a chimeric monoclonal antibody that is given intravenously every 4–8 weeks. Golimumab is a human monoclonal antibody to TNFα. The drug was derived from hybridomas generated from a transgenic mouse containing activated human immunoglobulin genes and inactivated mouse immunoglobulin genes for heavy chain and κ light chain.8 Results from a phase II study showed golimumab injections every 4 weeks effectively reduced the signs and symptoms of rheumatoid arthritis and improved physical function in patients with active disease on methotrexate.9
Development of a TNFα inhibitor with a more convenient dosing schedule than that of available drugs might be beneficial. Patients who do not respond to one TNFα inhibitor might benefit from switching to another. In the GO-AFTER (GOlimulab After Former anti-tumour necrosis factor α Therapy Evaluated in Rheumatoid arthritis) trial, we assessed the efficacy and safety of golimumab for patients with active rheumatoid arthritis who had previously received one or more TNFα inhibitors.
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Patients
Patients from 82 sites in ten countries (Austria, Australia, Canada, Finland, Germany, Netherlands, New Zealand, Spain, UK, and USA) were monitored as outpatients in clinics or hospitals between Feb 21, 2006, and Sept 26, 2007. Eligible patients (webappendix pp 1–2) were aged 18 years or older, and had been diagnosed with active rheumatoid arthritis (persistent disease activity with at least four swollen and four tender joints), according to the criteria of the American College of Rheumatology
Results
Figure 1 shows the trial profile. 461 patients were randomised, of whom 331 (72%) were enrolled in the USA and Canada, and 130 (28%) in Europe, Australia, or New Zealand. One patient on each of 50 mg and 100 mg golimumab was assigned but never received treatment; these patients were judged to have not achieved the primary efficacy endpoint. Table 1 shows the demographic and baseline disease characteristics of participants. Only eight (2%) patients had disease duration of less than 1 year.
Discussion
Our study shows that golimumab reduced the signs and symptoms of active rheumatoid arthritis and improved physical function in patients who had previously received TNFα inhibitors, which suggests that switching patients from one TNFα inhibitor to golimumab is effective and generally well tolerated.
The proportion of patients achieving ACR20 was maintained or increased slightly at each time point from week 4 to the primary endpoint at week 14, and further increased or stabilised during the
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