Background Efficacy and safety of TNFα inhibitors (TNFi) in rheumatoid arthritis (RA) have been evaluated in randomized controlled trials. The analysis of observational studies and registries provides additional real-world information. Drug survival rate reflects the real world balance between efficacy and safety.
Objectives The primary objective of this study was to compare the retention rates (RR) of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) as 1st-line biologic therapy in RA. The secondary objectives were to determine causes of discontinuation, factors associated with a better retention, and RR of 2d-line TNFi.
Methods This is a retrolective, multicentre study in 8 French Rheumatology centres. The medical charts of all pts with RA who started TNFi therapy between March 1st 2005 and April 30th 2009 were reviewed, based on diagnosis and treatment (TT) codes, with a follow-up duration of min. 2 to max. 6 yrs. The RR was estimated using the Kaplan-Meier method. TNFi were compared after adjusting the inverse of a propensity score, using a Cox model. Factors associated with a better RR were identified by multivariate analysis.
Results 706 pts were included in the study. The first TNFi was ADA in 203 (28.8%), ETN in 404 pts(57.2%) and IFX in 99 pts (14%). The percentage of pts still on TT after 2 yrs was 54.9%, 61.9% and 48.7% for ADA, ETN and IFX respectively. The median duration of trt was 31 mths for ADA (95% CI [19-38]), 45 mths for ETN (95% CI [35-51]) and 23 mths for IFX (95% CI [16-36]). The Hazard ratios (HRs) for discontinuing the first TNFi were significantly greater with ADA and IFX than with ETN (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828] respectively). There was no significant difference between the 2 monoclonal antibodies. The HR for TT discontinuation due to lack of efficacy was significantly higher with ADA than ETN (1.511, 95% CI [1.152-1.982]). The HR for stopping trt due to adverse events was significantly higher with IFX than ETN (2.175 (95% CI [1.402-3.374]). Baseline characteristics associated with a better retention of the first TNFi were a higher number of previous DMARDs and a higher ESR. A second TNFi was administered to 231 pts: ADA in 105, ETN in 106, and IFX in 20 pts. The median retention period was 11 mths for ADA (95% CI [7-17]), 43 mths for ETN (95% CI [19.1-58]), and 19.1 mths for IFX (95% CI [5-NE]). The HR for discontinuing ADA was significantly greater than for ETN (2.023, 95% CI [1.393-2.937]). The HRs for stopping due to lack of efficacy or adverse events (AE) were significantly greater for ADA than for ETN (1.998, 95% CI [1.321-3.024] and 2.188, 95% CI [1.017-4.708] respectively).
Conclusions ETN had a better RR as a first-line biotherapy in RA, with a HR for discontinuing ADA or IFX that was about 30% greater than that of ETN. As first-line biologic therapy, ETN had fewer withdrawals for inefficacy than ADA, and fewer withdrawals for AE than IFX. As a 2d-line TNFi, ETN also had a better RR than ADA.
Disclosure of Interest A. Frazier-Mironer Consultant for: Pfizer, A. Cantagrel Grant/research support from: Chugai, Pfizer, UCB, Consultant for: Laboratoires BMS, Chugai, MSD France, Novartis, Pfizer, Roche, UCB, Speakers bureau: Laboratoires Abbott, BMS, Chugai, MSD France, Nordic-Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, B. Combe Grant/research support from: Pfizer, Roche, Chugai, Consultant for: BMS, Celgene, Merck, Novartis, Pfizer, Roche, Chugai, UCB, Speakers bureau: Merck, Pfizer, UCB, V. Deschamps Employee of: PFIZER, M. Dougados Grant/research support from: Pfizer, Abbott, Roche, BMS, Merck, Lilly, Novartis, Consultant for: Pfizer, Abbott, Roche, BMS, Merck, Lilly, Novartis, R.-M. Flipo Grant/research support from: Pfizer, Roche, Chugaï, Consultant for: Abbott, Astra-Zeneca, BMS, Ipsen-Ménarini, MSD, Pfizer, Roche, Chugaï, UCB, Janssen-Cilag, Paid instructor for: Abbott, Astra-Zeneca, BMS, Expansciences, Ipsen-Ménarini, MSD, Nordic-Pharma, Pfizer, Roche, Chugaï, Genzyme, UCB, I. Logeart Employee of: Pfizer, X. Mariette Consultant for: BMS, Pfizer, Roche et UCB, T. Schaeverbeke Consultant for: Roche, Chugai, Pfizer, J. Sibilia Grant/research support from: Roche, Pfizer, Merck Sharp, Bristol Myers Squibb, Speakers bureau: Roche, Chugai, Bristol Myers Squibb, Abbott, UCB, GSK, LFB, Actelion, Pfizer, Merck Sharp, Novartis, X. Le Loët Consultant for: MSD, Pfizer, Roche