Mechanism | Example | Rat AIA | Rat CIA | Mouse CIA | References | |||
Prophylactic | Therapeutic | Prophylactic | Therapeutic | Prophylactic | Therapeutic | |||
Phase III: | ||||||||
TACE inhibitor | DPC 333 (BMS-561392) | + | + | Lorenz et al107 | ||||
Anti-cytokine, anti-T cell | Esonarimod | ++ | ++ | Noguchi et al108 | ||||
NSAID | Amiprilose | ++ | ++ | ++ | Kieval et al109 | |||
Increase T suppressor cells | Nuclomedone | + | − | Komoriya et al110 | ||||
PGE synthesis inhibitor | FK 3311 | + | + | Harris et al, Tsuji et al101 111 | ||||
MMP inhibitor | Cipemastat (Trocade) | − | – | − | Ishikawa et al112 | |||
Phase II | ||||||||
Th2 induction, NFκB inhibition | IL11 | + | + | + | Albert et al, Walmsley et al113 114 | |||
Decrease IL1 release | TOK-8801 | + | + | ++ | ++ | |||
VLA-4 antagonist | ZD-7349 | + | ||||||
Dual COX/LT inhibitor | Tepoxalin | + | Argentieri et al74 | |||||
Complement inhibitor (humanised anti-C5) monoclonal antibody) | Eculizumab (5G1.1) | + | Linton and Morgan, Wang et al24 115 | |||||
Antibody to IL12p40 | IL12 mAb (ABT 874) | + | ||||||
O2 radical scavenger | Superoxide dismutase | ++ | ++ | Shingu et al116 | ||||
P38 MAP kinase inhibitor | Doramapimod (BIRB 796) | + | Nabozny et al117 | |||||
P38 MAP kinase inhibitor | TAK 715 | + | Miwatashi et al118 | |||||
Bisphosphonate, IL1 antagonist | TRK 530 | + | + | Tanahashi et al, Takaoka et al119–121 | ||||
ICE inhibitor | Pralnacasan (VX740) | + | Linton, Ku et al122 123 | |||||
IL4 (B cell stimulatory factor 1) | IL4 | + | + | Cottard et al, Kim et al124 125 | ||||
Oral TNFα inhibitor | AGIX-4207 | + | Sundell et al126 | |||||
MCP-1 inhibitor | Bindarit | + | Guglielmotti et al127 | |||||
Immunomodulator | SM 8849 | ++ | ++ | + | Nagai et al128 | |||
IFNβ | Rebif | + | van Holten et al129 | |||||
Targets α (v) β 3 | RGD-4C_D(KLAKLAK)2 | + | Gerlag et al130 |
+, Efficacy; −, 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.
AIA, adjuvant-induced arthritis; CIA, collagen-induced arthritis; COX, cyclo-oxygenase; ICE, interleukin 1β converting enzyme; IFN, interferon; IL, interleukin; LT, leukotriene; mAb, monoclonal antibody; MAP, mitogen activated protein; MCP, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; NFκB, nuclear factor κB; NO, nitric oxide; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2; RA, rheumatoid arthritis; TACE, TNFα converting enzyme; Th, T helper; TNF, tumour necrosis factor; VLA-4, very late antigen-4.