Ann Rheum Dis 68:914-921 doi:10.1136/ard.2008.092254
  • Clinical and epidemiological research

Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis

  1. S M van der Kooij1,
  2. Y P M Goekoop-Ruiterman1,
  3. J K de Vries-Bouwstra2,
  4. M Güler-Yüksel1,
  5. A H Zwinderman3,
  6. P J S M Kerstens4,
  7. P A H M van der Lubbe5,
  8. W M de Beus6,
  9. B A M Grillet7,
  10. H K Ronday8,
  11. T W J Huizinga1,
  12. F C Breedveld1,
  13. B A C Dijkmans2,4,
  14. C F Allaart1
  1. 1
    Leiden University Medical Center, Leiden, The Netherlands
  2. 2
    VU Medical Center, Amsterdam, The Netherlands
  3. 3
    Academic Medical Center, Amsterdam, The Netherlands
  4. 4
    Jan van Breemen Institute, Amsterdam, The Netherlands
  5. 5
    Vlietland Hospital, Schiedam, The Netherlands
  6. 6
    Medical Center Haaglanden, Leidschendam, The Netherlands
  7. 7
    Hospital Zeeuws Vlaanderen, Terneuzen, The Netherlands
  8. 8
    Haga Hospital, The Hague, The Netherlands
  1. Dr S M van der Kooij, Department of Rheumatology C-01-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; smvanderkooij{at}
  • Accepted 10 July 2008
  • Published Online First 28 July 2008


Objectives: To compare the occurrence of drug-free remission, functional ability and radiological damage after 4 years of response-driven treatment according to four different treatment strategies for rheumatoid arthritis (RA).

Methods: Patients with recent-onset, active RA (n  =  508) were randomly assigned to four different treatment strategies: (1) sequential monotherapy; (2) step-up combination therapy; (3) initial combination therapy with prednisone and (4) initial combination therapy with infliximab. Treatment was adjusted based on 3-monthly disease activity score (DAS) assessments, aiming at a DAS ⩽2.4. From the third year, patients with a sustained DAS <1.6 discontinued treatment.

Results: In total, 43% of patients were in remission (DAS <1.6) at 4 years and 13% were in drug-free remission: 14%, 12%, 8% and 18% of patients in groups 1–4, respectively. The absence of anti-cyclic citrullinated peptide antibodies, male gender and short symptom duration were independently associated with drug-free remission. Functional ability and remission were maintained in all four groups with the continuation of DAS-driven treatment, without significant differences between the groups. Significant progression of joint damage was observed in 38% and 31% of patients in groups 3 and 4 versus 51% and 54% of patients in groups 1 and 2 (p<0.05, group 4 versus groups 1 and 2, group 3 versus group 2).

Conclusions: In patients with recent-onset active RA, drug-free remission was achieved in up to 18% of patients. DAS-driven treatment maintained clinical and functional improvement, independent of the treatment strategy. Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherapy.


  • Competing interests: Declared. CFA and FCB have received lecture fees from Schering-Plough; BACD has received funds for research and lecture fees from Schering-Plough.

  • Funding: This study was funded by a grant of the Dutch College of Health Insurances (College Voor Zorgverzekeringen) with additional funding provided by Schering-Plough, BV and Centocor, Inc. The authors, not the sponsors, were responsible for the study design, the collection, analyses and interpretation of all data, the writing of this article and the decision to publish.

  • Ethics approval: The medical ethics committee at each participating centre approved the study protocol, including the amendment for the extension phase.

  • Patient consent: Obtained.