At the plenary session, Dr. Roy Fleischmann presented a head-to-head study in active RA (MTX-IR) comparing certolizumab pegol (Cimzia) to adalimumab (Humira) added to MTX (Abstract #2987). This was a 2-year study but at 12 weeks there was a twist: non-responders (not achieving a change in DAS28 of 1.2 or not having a low DAS28 defined as <3.2), were switched to the alternate treatment. 915 patients were randomized and at 12 weeks approximately 80% in each arm responded. The others were crossed over to the alternate TNFi. This study was recently published in the Lancet.
The results were not different at 12 or 104 weeks. ACR20 response at week 12 (69% and 71%); and DAS28(ESR) low disease activity at week 104 (35.5% and 33.5%) for CZP+MTX and ADA+MTX, respectively. No differences between treatment arms were evident in secondary and exploratory efficacy endpoints.
So why was this a failed study? The analysis plan and power were calculated to show superiority of Cimzia over Humira and this did not occur. The efficacy results and even safety were not different between the two groups.
What did we learn?
Head-to-head trials within the same class of drugs in RA are expensive and risky
Some patients can go from one TNFi to another in a RCT and gain some benefit
Despite a great treatment class, only 1/3 of patients by 2 years are in a low disease state. So remission was not achieved in the VAST MAJORITY of patients, nor was even a low disease state. It makes you wonder why the patients stayed in the study, or what was driving the 2/3 to NOT be in a low disease state (i.e. pain, patient global, etc)?
Dr. Janet Pope is Professor of Medicine at Western University and Division Head of Rheumatology. Dr. Pope's research interests include epidemiologic studies in scleroderma, classification criteria in systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.View Full Bio