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Extended report
Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study
  1. Gülşah Akdemir1,
  2. Lotte Heimans1,
  3. Sytske Anne Bergstra1,
  4. Robbert J Goekoop2,
  5. Maikel van Oosterhout3,
  6. Johannes H L M van Groenendael4,
  7. André J Peeters5,
  8. Gerda M Steup-Beekman6,
  9. Leroy R Lard7,
  10. Peter B J de Sonnaville8,
  11. Bernard A M Grillet9,
  12. Tom W J Huizinga1,
  13. Cornelia F Allaart1
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  2. 2 Department of Rheumatology, Haga Hospital, Hague, Netherlands
  3. 3 Department of Rheumatology, Groene Hart Hospital, Gouda, Netherlands
  4. 4 Department of Rheumatology, Franciscus Hospital, Roosendaal, Netherlands
  5. 5 Department of Rheumatology, Reinier de Graaf Gasthuis, Delft, Netherlands
  6. 6 Department of Rheumatology, Bronovo Hospital, Hague, Netherlands
  7. 7 Department of Rheumatology, MCH Antoniushove, Hague, Netherlands
  8. 8 Department of Rheumatology, Admiraal de Ruyter Ziekenhuis, Goes, Netherlands
  9. 9 Department of Rheumatology, Zorgsaam, Terneuzen, Netherlands
  1. Correspondence to Gülşah Akdemir, Department of Rheumatology, Leiden University Medical Center, Leiden, P.O. BOX 9600 2300 RC, The Netherlands; g.akdemir{at}


Objectives To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis.

Methods In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years.

Results After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.

Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0–2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years.

Conclusions Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

  • early rheumatoid arthritis
  • treatment
  • disease activity remission
  • DMARDs (biologic)
  • DMARDs (synthetic)

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  • Handling editor Tore K Kvien

  • Contributors GA performed the statistical analysis, interpreted the data and drafted the manuscript. LH, SAB, RJG, MvO, JHLMvG, AJP, GMS-B, LRL, PBJdS and BAMG contributed in the acquisition of the data and revised the manuscript. TWJH participated in the study design, contributed in the acquisition of the data and was involved in revising of the manuscript. CFA participated in the study design, contributed in the acquisition of the data and was involved in analysing and interpreting the data and helped to draft the manuscript. All authors read and approved the final version of the manuscript.

  • Funding The study was designed by the investigators and financially supported during the first year of follow-up by AbbVie.

  • Disclaimer Trial management, data collection, patient recruitment, data analysis, interpretation and preparation of the manuscript were performed by the authors. We have not been paid to write this manuscript by a pharmaceutical company or other agency. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

  • Competing interests TWJH reports grants from AbbVie during the conduct of the study and grants from UCB, Bristol Myers Squibb, Pfizer, Roche, Sanofi-Aventis and Boeringher from outside the submitted work. The other authors declare no competing interests.

  • Patient consent Obtained.

  • Ethics approval The study protocol was approved by the medical ethical committees of all participating hospitals.

  • Provenance and peer review Not commissioned; externally peer reviewed.