Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody campath‐1h administered by daily subcutaneous injection

Abstract

Objective. To investigate the dose tolerance and potential clinical activity of a humanized antilymphocyte monoclonal antibody, CAMPATH‐1H (C1H), in patients with active, refractory rheumatoid arthritis (RA). Methods. Thirty adult patients with active, refractory RA were treated in an open‐label, 3‐center, dose‐escalation study of subcutaneously injected C1H. Six patients were assigned to each of 5 dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily injections of C1H over a 12‐day period. Results. Side effects occurred primarily during the first 1–2 days of dosing, and included mild fever, chills, nausea, vomiting, headache, and, in a minority of patients, hypotension. All patients developed some discomfort at the injection site. Self‐limited infections occurred in 5 patients during the 6‐month study period. Peripheral blood lymphocyte counts fell promptly after initial dosing and recovered slowly, usually over 2–3 months. Serum antibodies to C1H developed in 54% of patients following treatment. Clinical improvement was observed in 56% of patients, based on the composite Paulus criteria, with a median time‐to‐response of 22 days and a median response duration of 32 days. Conclusion. C1H is a lymphocyte‐depleting antibody that exhibits biologic potency when administered subcutaneously to patients with refractory RA. Its use is associated with mild to moderate toxicity and short‐term amelioration of disease activity.

Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab

“…17 As expected, profound and prolonged lymphopenia was observed in previous studies of Alemtuzumab in patients with advanced B cell malignancies or rheumatoid arthritis. [18][19][20] There has been a variable incidence of opportunistic infections. [18][19][20][21][22] The incidence of CMV infection following nonmyeloablative SCT containing fludarabine-based conditioning regimes but without anti-lymphocyte antibody has been reported to be from 21 to 53%.…”

“…[18][19][20] There has been a variable incidence of opportunistic infections. [18][19][20][21][22] The incidence of CMV infection following nonmyeloablative SCT containing fludarabine-based conditioning regimes but without anti-lymphocyte antibody has been reported to be from 21 to 53%. 23,24 The much higher incidence of CMV infections after RIC with Alemtuzumab has been reported previously.…”

A therapeutic human IgG4 monoclonal antibody that depletes target cells in humans

“…Depleting rat IgG2b gave slower repletion, similar to that seen with IgG4-C1H in the current study. Elsewhere, patients have received single doses of IgG1-C1H [16,28] 10 mg or more produced at least 90% depletion of PBL with slow recovery, median PBL exceeding 500 cells/mm 3 after a minimum of 2 months.…”

Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis

“…The demographic data of the patients are given in Table 1. The clinical characteristics and clinical responses of the entire study cohort of the multicenter trial are published elsewhere in this issue of Arthritis and Rheumatism (20).…”