SUCCESSFUL THERAPY OF COLLAGEN-INDUCED ARTHRITIS WITH TNF RECEPTOR-IGG FUSION PROTEIN AND COMBINATION WITH ANTI-CD4

We have previously shown that anti-tumour necrosis factor (TNF) monocl onal antibody (mAb) ameliorates established collagen-induced arthritis and that the efficacy of this form of treatment can be enhanced by co ncurrent anti-CD4 treatment. Here we assess the efficacy of a human p5 5 TNF receptor-IgG fusion protein (p55-sf2), given alone or with anti- CD4 mAb. TNF receptor-IgG fusion protein (100 mu g) suppressed paw swe lling and limb recruitment in established arthritis and reduced the in cidence of erosions in the proximal interphalangeal joints from 92% to 50%, which was comparable to 41% erosions using anti-TNF mAb. Methylp rednisolone acetate (42 mg/kg/week) reduced clinical signs of inflamma tion in a manner comparable to TNF blockade but had little effect on t he incidence of erosions. Go-administration of anti-CD4 and TNF recept or-IgG led to an even greater therapeutic effect than TNF receptor-IgG alone, with the incidence of erosions being reduced from 100% to 17%. Serological analyses showed that the beneficial effects of anti-CD4 a nd TNF receptor-IgG could be partly explained by the ability of anti-C D4 to prevent a neutralizing antibody response. These results confirm the importance of TNF in destructive inflammatory arthritis and demons trate the feasibility of therapeutically targeting TNF with a form of TNF receptor. Finally, the findings confirm the beneficial effects of TNF-targeted therapy coupled with anti-CD4 therapy.