Background: Treat-to-target therapy is effective for patients with rheumatoid arthritis (RA), but long-term results of continued targeted treatment are lacking. Objective: To evaluate long-term outcomes in patients with early RA after 10 years of targeted treatment in 4 treatment strategies. Design: Randomized trial. (Nederlands Trial Register: NTR262 and NTR265) Setting: The Netherlands. Patients: 508 patients with early active RA. Intervention: Sequential monotherapy (strategy 1), step-up combination therapy (strategy 2), or initial combination therapy with prednisone (strategy 3) or with infliximab (strategy 4), all followed by targeted treatment aiming at low disease activity. Measurements: Functional ability (Health Assessment Questionnaire [HAQ] score) and radiographic progression (Sharp-van der Heijde score) were primary end points. Survival in the study population was compared with the general population using the standardized mortality ratio. Results: 195 of 508 of patients (38%) dropped out of the study (28% in strategy 4 vs. 40% to 45% in strategies 1 to 3, respectively). At year 10, mean HAQ score (SD) was 0.57 (0.56); 53% and 14% of patients were in remission and drug-free remission, respectively, without differences among the strategies. Over 10 years, mean HAQ scores were 0.69, 0.72, 0.64, and 0.58 in strategies 1 to 4, respectively (differences not clinically relevant). Radiographic damage was limited for all strategies, with mean Sharp-van der Heijde estimates during follow-up of 11, 8, 8, and 6 in strategies 1 to 4, respectively (P = 0.15). Standardized mortality ratio was 1.16 (95% CI, 0.92 to 1.46) based on 72 observed and 62 expected deaths, with similar survival among the 4 strategies (P = 0.81). Limitation: Dropout rate varied by strategy. Conclusion: In patients with early RA, initial (temporary) combination therapy results in faster clinical improvement and targeted treatment determines long-term outcomes. Drug-free remission, with prevention of functional deterioration and clinically relevant radiographic damage, and normalized survival are realistic outcomes.

doi.org/10.7326/M15-0919, hdl.handle.net/1765/89564
Annals of Internal Medicine

Markusse, I. M., Akdemir, G., Dirven, L., Goekoop-Ruiterman, Y. P. M., van Groenendael, J. H. L. M., Han, H., … Allaart, C. (2016). Long-term outcomes of patients with recent-onset rheumatoid arthritis after 10 years of tight controlled treatment: A randomized trial. Annals of Internal Medicine, 164(8), 523–531. doi:10.7326/M15-0919