TY - JOUR
T1 - Long-Term Outcomes of Patients With Recent-Onset Rheumatoid Arthritis After 10 Years of Tight Controlled Treatment
T2 - A Randomized Trial
AU - Markusse, Iris M.
AU - Akdemir, Gulsah
AU - Dirven, Linda
AU - Goekoop-Ruiterman, Yvonne P. M.
AU - van Groenendael, Johannes H. L. M.
AU - Han, K. Huub
AU - Molenaar, T. H. Esmeralda
AU - Le Cessie, Saskia
AU - Lems, Willem F.
AU - van der Lubbe, Peter A. H. M.
AU - Kerstens, Pit J. S. M.
AU - Peeters, Andre J.
AU - Ronday, H. Karel
AU - de Sonnaville, Peter B. J.
AU - Speyer, Irene
AU - Stijnen, Theo
AU - ten Wolde, Saskia
AU - Huizinga, Tom W. J.
AU - Allaart, Cornelia F.
PY - 2016/4/19
Y1 - 2016/4/19
N2 - 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.PRIMARY FUNDING SOURCE: Dutch College of Health Insurance Companies, Schering-Plough, and Janssen.
AB - 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.PRIMARY FUNDING SOURCE: Dutch College of Health Insurance Companies, Schering-Plough, and Janssen.
KW - Antibodies, Monoclonal
KW - Antirheumatic Agents
KW - Arthritis, Rheumatoid
KW - Disease Progression
KW - Drug Therapy, Combination
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Infliximab
KW - Male
KW - Middle Aged
KW - Prednisone
KW - Remission Induction
KW - Survival Analysis
KW - Treatment Outcome
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.7326/M15-0919
DO - 10.7326/M15-0919
M3 - Article
C2 - 27089068
VL - 164
SP - 523
EP - 531
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 8
ER -