Background Recent studies showed diverging results about mortality trends in patients with rheumatoid arthritis (RA).
Objectives Our aim was to determine survival after 10 years of treat-to-target therapy in patients with early RA, to compare these survival rates with the general population and to define risk factors for mortality during the 10 years duration of the BeSt study.
Methods The BeSt study enrolled 508 Dutch patients with early active RA (1987 criteria) who were randomized to: sequential monotherapy, step-up therapy, initial combination including either prednisone or infliximab. During 10 years, all patients were treated-to-target, aiming at a disease activity score (DAS) ≤2.4. Kaplan-Meier curves and the log-rank test were used to compare survival rates in the four treatment strategies. Standardized mortality ratios (SMR) were used to compare the BeSt population to the general Dutch population, matched by age, gender and calendar year. Cox regression analysis was used to calculate hazard ratios (HR) to determine baseline risk factors for increased mortality in the BeSt population. Time dependent Cox regression analysis was used to study DAS during follow-up as a risk factor for mortality.
Results During 10 years, 72 of 508 patients died at a mean age of 75 years. No difference in survival was observed between the treatment strategies (p=0.805) (figure), with 16/126, 15/121, 21/133 and 20/128 deaths in arm 1 to 4, respectively. Based on the general Dutch population, 62 deaths were expected and 72 deaths occurred, resulting in an overall SMR of 1.16 (95% confidence interval, CI 0.92 – 1.46). Comparing the general population to each of the treatment strategies resulted in a SMR (95% CI) of 1.00 (0.61–1.64), 1.02 (0.61–1.69), 1.30 (0.85–1.99) and 1.32 (0.85–2.04) in arm 1 to 4, respectively.
In the BeSt population, baseline age (HR 1.13, 95% CI 1.10-1.16), male gender (HR 1.78, 95% CI 1.06-2.99), smoking at baseline (HR 5.19, 95% CI 3.08-8.75) and health assessment questionnaire at baseline (HR 1.89, 95% CI 1.29-2.76) were associated with an increased risk of mortality. Randomization arm was not associated with an increased risk of mortality (arm 1 as reference category; arm 2 HR 0.99, 95% CI 0.49–2.00; arm 3 HR 1.27, 95% CI 0.66–2.44; arm 4 HR 1.25, 95% CI 0.65–2.41). DAS over time showed a trend (HR 1.23, 95% CI 0.96–1.58).
Conclusions After 10 years of continued tight controlled treatment in patients with rheumatoid arthritis in the BeSt study, the survival rate was comparable to the general Dutch population, without significant differences between the treatment strategies. Higher age, male gender, smoking and worse functional ability were associated with an increased mortality risk within our study population, as in the general population. These results suggest that treatment targeted at DAS ≤2.4 prevents excess mortality during 10 years after diagnosis, and that the medication used in these strategies does not increase mortality.
Disclosure of Interest I. Markusse: None declared, L. Dirven: None declared, H. Han: None declared, K. Ronday: None declared, I. Speyer: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, C. Allaart Grant/research support from: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.
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