RA TNF Antagonists
Abstract 676: A Difference in Effectiveness Between Infliximab, Etanercept and Adalimumab in Patients with Rheumatoid Arthritis
AUTHORS: W Kievit, J Fransen, IH Kuper, MAFJ van de Laar, TL Jansen, DjRAM de Rooij, CM de Gendt, KH Ronday, HLM Brus, PCM van Ooijen, PCLM. van Riel
BACKGROUND: There have been to date no head to head comparisons of TNF antagonists in patients with RA. Etanercept, adalimumab, and infliximab combined with MTX have demonstrated very similar responses based on signs and symptoms, radiographic progression, and functional outcomes in patients with both early and with established RA. This was a study from the Netherlands reporting the 12 month EULAR responses of patients starting on TNF antagonists and followed every 3 months.
METHODS: Patients who were starting on all three approved TNF antagonists were enrolled in the Dutch Rheumatoid Arthritis Anti-TNFα Monitoring (Dream) study and were monitored and assessed by a trained research nurse every three months. Patients were followed who were enrolled on their first TNF antagonist only. EULAR responses were calculated as were mean changes in DAS28 and HAQ over 3, 6 and 12 months Analyses were intent to treat (ITT) with last observation carried forward (LOCF).
RESULTS: The baseline clinical characteristics of patients starting each of the three TNF antagonists were similar with 78.8% RF positive, 70.4% women, and a mean age of 55.8 years. Patients had longstanding disease with a mean duration of 9.7 years, moderate disability (mean HAQ 1.4), and high levels of baseline disease activity (mean DAS28 5.3). Patients had been treated with a mean of 3.2 prior DMARDS. It is notable that the percentages of patients on methotrexate were similar in the different groups (59.3% Adalimumab, 51.5% Etanercept, 52.8% Infliximab), even though infliximab is indicated to be prescribed with MTX. The DAS28 declined in all groups over time showing but at all points, higher disease activity was observed in the infliximab group compared to etanercept and adalimumab with decreases from baseline in DAS 28 of 1.1, 1.7, and 1.7 in infliximab, etanercept, and adalimumab groups respectively. At 12 months more etanercept and adalimumab patients had achieved EULAR good/moderate responses (Ada 98%, Etanercept 96%, Infliximab 74%). At both 6 months and 12 months, reductions in HAQ were observed for each drug. For adalimumab, etanercept and infliximab, the changes in HAQ from baseline to 6 months were 0.41, 0.34, and 0.22, respectively and the change from baseline to 12 months was 0.45, 0.24, and 0.15, respectively.
CONCLUSION: When comparing the initial response to three TNF-alpha antagonists in patients with RA, reductions of disease activity and functional status were observed with all agents. The magnitude of responses for adalimumab and etanercept patients was higher than infliximab treated patients.
EDITORIAL COMMENT: Because we have no head to head comparisons of different TNF antagonists, investigators have reported the results from longitudinal registries and databases to assess differences between agents. When one looks at data obtained from registries one must also be careful in interpreting the data, especially as patients are not randomized to different treatments, thus there is significant bias that may be introduced into the results reported. This study shows that all three TNF antagonists provide improvements in RA disease activity, and function as would be expected. However some differences were observed between agents. Although the patients were well matched at baseline, there may have been other unmeasured factors or confounders that determined which patients received a particular therapy and thus affected the results that were seen. It is important to note that only 52% of patients who received Infliximab were also receiving MTX as indicated (and as previously studied), thus potentially accounting for the lower responses seen with this drug compared to other agents.
