A 24 week study of subcutaneous (sq) dosing with titration of CAMPATH-1H (C1H) dose against the circulating CD4+ T cell count in patients with rheumatoid arthritis (RA) was undertaken to examine the safety, biologic activity, and clinical efficacy of this approach.
All patients met American Rheumatism Association (ARA) criteria for active RA. Patients received either 0.5 or 1.0 mg of C1H subcutaneously twice per week; dosing could be doubled after the first 8 weeks of treatment and subsequently following 4 week dose intervals for lack of clinical efficacy, but was discontinued any time the CD4+ T cell count fell below 400/mm3. Patients were evaluated weekly for 2 weeks and then biweekly for clinical and laboratory variables of safety, biological activity, and disease activity.
Ten patients were treated, 6 in the 0.5 mg cohort and 4 in the 1.0 mg cohort. Four of ten patients had a 20% modified Paulus response (2 in each cohort) while taking drug; there were minimal side effects, primarily limited to local reaction at the injection site. All patients had a > 50% drop in circulating CD4+ T cells within the first 2 weeks of therapy, with no further significant reduction; only 1/6 patients in the 0.5 mg cohort had dose limiting CD4+ T cell depression vs 2/4 in the 1.0 mg cohort. All patients developed antibodies to C1H. Appearance of anti-C1H was temporarily associated with a halt in further reduction of CD4+ T cell count despite continued C1H administration.
Subcutaneous administration of C1H in low doses (0.5 mg biweekly) was well tolerated and did not result in dose limiting CD4+ T cell depletion in 5 of 6 patients. Clinical efficacy was observed in some patients but could not be maintained, possibly due to the production of anti-C1H antibodies.