Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody. Long-term followup of CD4+ T cell counts.
OBJECTIVE
To evaluate CD4+ T cell counts of rheumatoid arthritis (RA) patients at 18 and 30 months after treatment with a chimeric anti-CD4 monoclonal antibody (MAb), cM-T412, in a phase I trial.


METHODS
Of the 25 RA patients who received the MAb, 23 were available for followup at 18 and 30 months. Levels of circulating CD4+ T cells were measured by flow cytometry.


RESULTS
Circulating CD4+ T cell levels in these 23 RA patients remained below normal at 18 and 30 months posttreatment. More profound CD4+ T cell depletion was noted in the higher-dose groups (300 and 700 mg).


CONCLUSIONS
Prolonged suppression of circulating CD4+ T cells was noted both in single-infusion and multiple-infusion groups 18 and 30 months after cM-T412 treatment. The depression was more pronounced in patients who received multiple infusions of cM-T412. The prolonged decrease in CD4+ T cell numbers suggests that the capacity to reconstitute CD4+ T cells in this patient population (treated with methotrexate) is limited. One patient, who was also receiving methotrexate and prednisone, died 18 months after receiving 100 mg of cM-T412. No other significant adverse effects, in particular, no opportunistic infections, were reported in these 23 RA patients at 18 and 30 months of followup.
Moreland
L W
LW
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham 35294-0006.
Pratt
P W
PW
Bucy
R P
RP
Jackson
B S
BS
Feldman
J W
JW
Koopman
W J
WJ
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens