Long-Term Outcomes of Patients With Recent-Onset Rheumatoid Arthritis After 10 Years of Tight Controlled Treatment: A Randomized Trial

Iris M. Markusse, Gulsah Akdemir, Linda Dirven, Yvonne P. M. Goekoop-Ruiterman, Johannes H. L. M. van Groenendael, K. Huub Han, T. H. Esmeralda Molenaar, Saskia Le Cessie, Willem F. Lems, Peter A. H. M. van der Lubbe, Pit J. S. M. Kerstens, Andre J. Peeters, H. Karel Ronday, Peter B. J. de Sonnaville, Irene Speyer, Theo Stijnen, Saskia ten Wolde, Tom W. J. Huizinga, Cornelia F. Allaart

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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.

Original languageEnglish
Pages (from-to)523-531
Number of pages9
JournalAnnals of Internal Medicine
Issue number8
Publication statusPublished - 19 Apr 2016


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Arthritis, Rheumatoid
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Infliximab
  • Journal Article
  • Male
  • Middle Aged
  • Multicenter Study
  • Prednisone
  • Randomized Controlled Trial
  • Remission Induction
  • Research Support, Non-U.S. Gov't
  • Survival Analysis
  • Treatment Outcome

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