Table 3 Efficacy (therapeutic or prophylactic) in animal models of rheumatoid arthritis (RA) of drugs suspended from phase II or III clinical development as treatments for RA
MechanismExampleRat AIARat CIAMouse CIAReferences
ProphylacticTherapeuticProphylacticTherapeuticProphylacticTherapeutic
Phase III:
TACE inhibitorDPC 333 (BMS-561392)++Lorenz et al107
Anti-cytokine, anti-T cellEsonarimod++++Noguchi et al108
NSAIDAmiprilose++++++Kieval et al109
Increase T suppressor cellsNuclomedone+Komoriya et al110
PGE synthesis inhibitorFK 3311++Harris et al, Tsuji et al101 111
MMP inhibitorCipemastat (Trocade)Ishikawa et al112
Phase II
Th2 induction, NFκB inhibitionIL11+++Albert et al, Walmsley et al113 114
Decrease IL1 releaseTOK-8801++++++
VLA-4 antagonistZD-7349+
Dual COX/LT inhibitorTepoxalin+Argentieri et al74
Complement inhibitor (humanised anti-C5) monoclonal antibody)Eculizumab (5G1.1)+Linton and Morgan, Wang et al24 115
Antibody to IL12p40IL12 mAb (ABT 874)+
O2 radical scavengerSuperoxide dismutase++++Shingu et al116
P38 MAP kinase inhibitorDoramapimod (BIRB 796)+Nabozny et al117
P38 MAP kinase inhibitorTAK 715+Miwatashi et al118
Bisphosphonate, IL1 antagonistTRK 530++Tanahashi et al, Takaoka et al119121
ICE inhibitorPralnacasan (VX740)+Linton, Ku et al122 123
IL4 (B cell stimulatory factor 1)IL4++Cottard et al, Kim et al124 125
Oral TNFα inhibitorAGIX-4207+Sundell et al126
MCP-1 inhibitorBindarit+Guglielmotti et al127
ImmunomodulatorSM 8849+++++Nagai et al128
IFNβRebif+van Holten et al129
Targets α (v) β 3RGD-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.