Background Drug retention is considered an indicator of the overall effectiveness, safety and tolerability of a treatment. It is a useful guide to decide the best anti-TNF therapy in patients with R.A.
Objectives To determine which of the TNF inhibitors has the highest retention rate in patients with R.A and to analyze the different reasons for drug discontinuation.
Methods A search of MEDLINE, CENTRAL and EMBASE identified 201 randomized controlled trials (RCTs). We included those comparing a TNF inhibitor (standard dose) with a placebo group, plus concomitant use of conventional DMARDs. We excluded those allowing rescue therapy or not reporting the outcomes of interest. These outcomes were: drug discontinuation and reasons, adverse events, serious adverse events, infections, serious infections and acute infusion events or injection site reactions. A mixed-treatment comparisons analysis was constructed to indirectly compare each study group to one another. Calculation of the probability that each treatment is best was implemented using the Bayesian Markov chain Monte Carlo method.
Results 18 RCTs, including 6948 patients, were extracted. The mean length of study was 6.6 months. On average, patients were 52 years old with active R.A of 5.5 years duration, with 24 TJC, 15 SJC and CRP of 2.3 mg/dl at baseline.
All TNF inhibitors were associated with relatively high rates of drug survival and no statistically significant differences were noted. By rank probability, Infliximab had the highest probability (52%) of retaining patients, and Golimumab (26%) and Certolizumab (29%) had the highest probabilities of being least likely to retain patients (see graphic). Regarding discontinuation due to lack/loss of efficacy, Certolizumab was the most likely and Infliximab the least likely drug to be discontinued. With respect to discontinuation due to adverse events, Infliximab had a 77% probability of being the most likely drug to be discontinued and Certolizumab (30%) was the least likely drug to be discontinued. Additionally, regarding adverse event-related outcomes, several observations were notable. Both Adalimumab and Golimumab were statistically significantly less likely than Infliximab to cause infections and, by rank probability, Infliximab had a 96% chance of being the drug most likely to cause infections. Regarding infusion/injection reactions, both Certolizumab and Infliximab were associated with very high probabilities (51% and 47%, respectively) relative to the other agents of being most likely to cause infusion reactions.
Conclusions Infliximab had the highest retention rate and was the least likely drug to be discontinued due to lack or loss of efficacy, but had the highest discontinuation rate due to adverse events. More data is needed with longer study periods to further reinforce these findings.
Neovius M, Arkema E V, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum Dis 2013; 0: 1–7
Acknowledgement To Helene Walcoff, Medical Librarian, for helping with the literature search.
Disclosure of Interest None declared