Compound | Rat AIA | Rat CIA | Mouse CIA | Mechanism | References | |||
Prophylactic | Therapeutic | Prophylactic | Therapeutic | Prophylactic | Therapeutic | |||
Methotrexate | + | − | + | + | DMARD | Walz et al, Sakuma et al, Magari et al, Jaffee et al, Williams et al, Neurath et al54–59 | ||
Ciclosporine A | + | + | − | + | − | DMARD | Williams et al, Takagishi et al, Phadke et al, Magari et al, Theisen-Popp et al, Kaibara et al, Cannon et al37 50 51 56 60–62 | |
Gold compounds | +/− | +/− | − | DMARD | Probert et al, Carlson et al, Phadke et al, Cannon et al36 38 51 63 | |||
Penicillamine | + | +/− | − | DMARD | Probert et al, Carlson et al, Phadke et al, Lewis et al, Nishikaku and Koga36 38 51 64 65 | |||
Prednisone | + | + | + | Corticosteroid | Walz et al, Ward and Cloud, Sloboda et al, Paska et al54 66 67 68 | |||
Cyclophosphamide | + | − | +/− | + | Antimetabolite | Probert et al, Cannon et al, Walz et al, Cannon et al, Sloboda et al36 49 54 62 67 | ||
Indomethacin | + | + | + | NSAID | Probert 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 69–72 | |||
Naproxen | + (d10) | + | − | NSAID | Phadke et al, Bendele et al, Argentieri et al, Takashita et al51 73–75 | |||
Celecoxib | + | COX-2 inhibitor | Penning et al76 | |||||
Rofecoxib (withdrawn) | + | COX-2 inhibitor | Chan et al77 | |||||
Flobufen | + | Dual COX/LT inhibitor | Bulej et al78 | |||||
Anakinra | + (d8) | + | + | IL1 receptor antagonist | Bendele et al, Joosten et al22 79 80 | |||
Etanercept (human sTNFR-Ig) | +/− | + | + | TNF blockade | Wooley et al, Bendele et al, McComb et al, Bendele et al, Williams et al42 79 81–83 | |||
Abatacept (CTLA4-Ig) | + | + | Blocks T cell costimulation | Williams et al, Webb et al83 85 | ||||
Toclizumab (MRA) | + | IL6 receptor antagonist* | Takagi et al86 | |||||
Approved in Japan: | ||||||||
Mizoribine | ++ | ++ | + | DNA synthesis inhibitor | Kamada et al87 88 | |||
Actarit | + | + | IL2 agonist | Fujisawa et al89 | ||||
FK 506 (tacrolimus) | + | + | ++ | ++ | Immunosuppressant | Sakuma et al, Magari et al, Arita et al, Takagishi et al55 56 90 91 | ||
Iguratimod (Y-614) | + | + | COX-2, TNF inhibitor | Inaba 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.