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Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis
  1. J S Dekkers1,
  2. J W Schoones2,
  3. T W Huizinga1,
  4. R E Toes1,
  5. A H van der Helm-van Mil1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Jacqueline S Dekkers, Department of Rheumatology, postzone C1-R, Leiden University Medical Center, P.O. Box 9600, Leiden 2300 RC, The Netherlands; j.s.dekkers{at}


Objective Current research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models.

Methods Eight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development).

Results Out of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor.

Conclusions Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.

  • Rheumatoid Arthritis
  • Arthritis
  • Autoantibodies
  • Autoimmunity

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  • Handling editor Tore K Kvien

  • Contributors JSD and JWS collected the data. JSD performed the analysis. AHMvdH-vM, TWH and RET supervised the project. All authors wrote and approved the manuscript.

  • Funding The authors acknowledge the financial support from the Dutch Arthritis Foundation, The Netherlands Organization for Scientific Research, the IMI JU funded project BeTheCure, contract no 115142-2. The work of AHMvH-vM was supported by a ZON-MW Vidi grant.

  • Competing interests None declared.

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

  • Data sharing statement All relevant data are within the paper and its online supplementary information files.