CD4 ANTIBODY TREATMENT IN PATIENTS WITH ACTIVE CROHNS-DISEASE - A PHASE-1 DOSE-FINDING STUDY

Background-T cells play an important part in Crohn's disease. Immunomo dulating therapies that target T cell activation may have clinical eff ects in Crohn's disease. Aim-To investigate the toxicity and potential efficacy of anti-CD4 monoclonal antibody therapy in patients with Cro hn's disease. Patients and methods-A dose escalating pilot study was c onducted in three groups of four patients with intractable Crohn's dis ease, refractory to steroids. They received 70, 210, or 700 mg of cM-T 412, a depleting anti-CD4 monoclonal antibody (mAb). Results-The mean reduction in Crohn's disease activity index (CDAI) was respectively 25 %, 24%, and 36% at four weeks, and 24% and 52% at 10 weeks in the 210 mg and 700 mg groups. There was only a minor effect on endoscopically evaluated disease activity. Side effects were mild to moderate fever w ith chills and headache. No signs of opportunistic infection were seen . There was a sustained decrease in CD4 count which lasted at least fo ur weeks in the 70 mg group (76 . 3 (SD 40 . 6)% of the baseline value ) and 10 weeks in both the 210 mg group (80 . 8 (SD 60 . 9)%) and the 700 mg group (24 . 8 (SD 15 . 4)%). The primary and secondary humoral immune response was not influenced by anti-CD4 mAb treatment. Conclusi on-This study shows the moderate potential efficacy of treatment of pa tients with Crohn's disease using a depleting chimeric monoclonal anti -CD4 antibody.