Table 4 Efficacy (therapeutic or prophylactic) of approved rheumatoid arthritis (RA) therapies in rat AIA, rat CIA and mouse CIA
CompoundRat AIARat CIAMouse CIAMechanismReferences
ProphylacticTherapeuticProphylacticTherapeuticProphylacticTherapeutic
Methotrexate+++DMARDWalz et al, Sakuma et al, Magari et al, Jaffee et al, Williams et al, Neurath et al5459
Ciclosporine A+++DMARDWilliams et al, Takagishi et al, Phadke et al, Magari et al, Theisen-Popp et al, Kaibara et al, Cannon et al37 50 51 56 6062
Gold compounds+/−+/−DMARDProbert et al, Carlson et al, Phadke et al, Cannon et al36 38 51 63
Penicillamine++/−DMARDProbert et al, Carlson et al, Phadke et al, Lewis et al, Nishikaku and Koga36 38 51 64 65
Prednisone+++CorticosteroidWalz et al, Ward and Cloud, Sloboda et al, Paska et al54 66 67 68
Cyclophosphamide++/−+AntimetaboliteProbert et al, Cannon et al, Walz et al, Cannon et al, Sloboda et al36 49 54 62 67
Indomethacin+++NSAIDProbert et al, Walz et al, Theisen-Popp et al, Cannon et al, Nishikaku and Koga, Ward and Cloud, Winter and Nuss, Yamaki et al, Griswold et al, Inou et al36 54 60 62 65 66 6972
Naproxen+ (d10)+NSAIDPhadke et al, Bendele et al, Argentieri et al, Takashita et al51 7375
Celecoxib+COX-2 inhibitorPenning et al76
Rofecoxib (withdrawn)+COX-2 inhibitorChan et al77
Flobufen+Dual COX/LT inhibitorBulej et al78
Anakinra+ (d8)++IL1 receptor antagonistBendele et al, Joosten et al22 79 80
Etanercept (human sTNFR-Ig)+/−++TNF blockadeWooley et al, Bendele et al, McComb et al, Bendele et al, Williams et al42 79 8183
Abatacept (CTLA4-Ig)++Blocks T cell costimulationWilliams et al, Webb et al83 85
Toclizumab (MRA)+IL6 receptor antagonist*Takagi et al86
Approved in Japan:
Mizoribine+++++DNA synthesis inhibitorKamada et al87 88
Actarit++IL2 agonistFujisawa et al89
FK 506 (tacrolimus)++++++ImmunosuppressantSakuma et al, Magari et al, Arita et al, Takagishi et al55 56 90 91
Iguratimod (Y-614)++COX-2, TNF inhibitorInaba et al92
  • +, Demonstrated efficacy; +/−, efficacy in some, but not all, studies; −, no effect. Where there is a ++ sign covering prophylactic and therapeutic efficacy, efficacy was demonstrated but it was not possible to determine whether it was prophylactic or therapeutic efficacy from the information available.

  • *, Positive in monkey CIA. IL6 deficient mice are resistant to CIA.

  • AIA, adjuvant-induced arthritis; CIA, collagen-induced arthritis; COX, cyclo-oxygenase; DMARD, disease-modifying antirheumatic drug; IL, interleukin; LT, leukotriene; NSAID, non-steroidal anti-inflammatory drug; TNF, tumour necrosis factor.