Background Current rheumatoid arthritis (RA) treatment guidelines recommend treating patients early according to the treat to target principle aiming for remission with a “step-up” treatment paradigm to biologics after failure of disease-modifying antirheumatic drugs (DMARDs). However, despite significant improvements in disease management, most patients have persistent disease activity, significant joint damage and disability. The risk of serious infections could be one of the concerns about using biologics earlier in the treatment paradigm.
Objectives To explore the efficacy and safety of earlier intervention, we reviewed the frequency of remission and serious infection events (SIEs) in DMARD-naïve and DMARD-inadequate responders (IR) in randomised, controlled clinical trials of approved biologics.
Methods A PubMed search up to January 2015 was performed for randomised, double-blind, placebo-controlled, multi-centre trials of all approved biologics in combination with methotrexate (MTX), in RA subjects that were either DMARD-naïve or DMARD-IR. All trials had to include disease activity score (DAS)28(CRP or ESR) remission (DAS28<2.6) data and were of at least 24 week duration. Outcomes analysed were frequencies of DAS remission and SIE.
Results 15 DMARD-naïve and 9 DMARD-IR trials were identified. Subjects in DMARD-naïve trials tended to be younger with shorter disease duration and lower baseline DAS28 than those in DMARD-IR trials. In DMARD-naïve subjects, the frequency of DAS28-ESR at 6 months was 39% for biologic + MTX and 21% for placebo + MTX; and 16% and 3% in DMARD-IR subjects, respectively. SIEs were slightly higher in both populations when using biologic + MTX, compared with MTX alone, but there was no apparent difference between DMARD-naive and DMARD-IR populations, although the numbers are relatively small and duration of treatment relatively short.
Conclusions Overall most patients do not achieve remission with biologics and there is much scope for improvement. The frequency of remission was higher in DMARD-naïve subjects than DMARD-IR subjects; however there were no apparent differences in serious infections across the two populations. These findings demonstrate that there remains a significant unmet need for more effective therapeutic strategies for RA in both DMARD-naïve and DMARD-IR populations.
Disclosure of Interest P. Mehta: None declared, K. Davy Shareholder of: GSK, Employee of: GSK, R. Williamson Shareholder of: GSK, Employee of: GSK, R. Rao Shareholder of: GSK, Employee of: GSK, P.-P. Tak Shareholder of: GSK, Employee of: GSK