Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.