Current strategies for the management of rheumatoid arthritis (RA) include control of rheumatoid inflammation as soon and as efficiently as possible, slowing progression of structural damage and restoring patients’ functionality while assuring short- and long-term safety.1 2

Despite the approval of tumour necrosis factor (TNF) inhibitors within the past decade and the development of biological agents with a different mode of action, new drugs are currently being developed with the goal to improve efficacy, reduce side effects or to allow a more convenient application considering the patient’s needs. There is also a clear need for efficacious drugs at lower costs than current biological treatment.

Up to now, randomised and placebo-controlled trials have formed the cornerstone of new drug development. In RA, a typical trial enrols patients for whom methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs) had previously failed, even though a precise definition of therapeutic failure is missing. Typically, patients undergo a washout period of concomitant DMARD treatment, which almost inevitably leads to a high mean baseline Disease Activity Score (DAS), that would otherwise be considered inadequate with regard to standards of care. Regulatory agencies have often required a duration of the placebo-controlled treatment phase of 24 weeks; however, more recently, trials have allowed escape rules for patients not achieving early improvement at week 16.

In this issue of the Annals of the Rheumatic Diseases, Maarten Boers concludes from his meta-analysis of trials using biological agents in RA that the time for 6-month placebo trials has now passed (see article on page 186).3 His analysis is based on 20 trials including 15 placebo and 18 active control cohorts comprising more than 10 000 patients. For placebo controlled trials, he elegantly demonstrates that ACR20 and ACR50 levels clearly differ already after 3 months and the mean difference …