title: Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis.
abstract: 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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Dekkers
authors.affiliation: Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Schoones
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D003094:Collagen / Q000633:toxicity; D004195:Disease Models, Animal
chemical_list: D000276:Adjuvants, Immunologic; D018501:Antirheumatic Agents; D003094:Collagen
keywords: Arthritis; Autoantibodies; Autoimmunity; Rheumatoid Arthritis