CAMPATH-1H in rheumatoid arthritis--an intravenous dose-ranging study.
Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATH is a trademark of Glaxo-Wellcome group companies, registered in the US Patent and Trademark Office) over 5 or 10 days in an open, uncontrolled study. Following therapy, patients were monitored for adverse effects and disease activity for 6 months. Therapy was associated with prolonged peripheral blood lymphopenia in all dosing cohorts. During the month immediately following therapy, lymphopenia was most profound in the 400 mg cohorts. The first dose of monoclonal antibody (Mab) was associated with a 'flu'-like syndrome, more pronounced at higher initial doses. One patient developed haemolytic-uraemic syndrome. There were a number of dose-related infections during the early post-treatment period and one fatal opportunistic infection which followed additional immunosuppressive therapy. Antiglobulin responses developed in 9 of 31 patients tested. The majority of patients showed symptomatic improvement following therapy and 20% of patients maintained a 50% Paulus response at 6 months, all of whom were in the 250 or 400 mg cohorts. CAMPATH-1H appears to be an effective treatment for RA. Allowing for the small number of patients treated, infections were more common with higher doses, although this was not true for adverse events overall, and therapeutic responses were more sustained at higher dosing levels. The broad specificity of CAMPATH-1H may be appropriate for the immunotherapy of RA and future studies should aim to define a dose with an optimal therapeutic ratio.
Isaacs
J D
JD
Addenbrooke's NHS Trust, Cambridge, UK.
Manna
V K
VK
Rapson
N
N
Bulpitt
K J
KJ
Hazleman
B L
BL
Matteson
E L
EL
St Clair
E W
EW
Schnitzer
T J
TJ
Johnston
J M
JM
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007596:Joints / Q000503:physiopathology; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab