Browse by author
Lookup NU author(s): Professor John IsaacsORCiD
Background: Immunological tolerance in humans using anti-T-cell monoclonal antibodies (mAbs) may be hampered by a pro-inflammatory microenvironment. All clinical trials of such therapies in rheumatoid arthritis (RA), however, have selected patients with active disease at baseline. Concurrent neutralization of inflammation with a TNF antagonist should maximize the potential of anti-T-cell mAbs to induce tolerance in RA. Aim: To evaluate the safety of combining a TNF antagonist and CD4 mAb in RA. Design: An iterative pilot study focused on the safety of such combination therapy. Methods: Eight poor prognosis, seropositive RA patients were treated with combined CD4 and TNF blockade. Prolonged CD4 blockade was achieved with a humanized mAb, and TNF blockade with a p55 TNF receptor fusion protein. Results: There was a low incidence of classical first-dose reactions to the CD4 mAb, possibly reflecting concomitant TNF blockade. An unusual anaphylactoid reaction was seen, however, and one patient developed a probable allergic reaction after several infusions. Skin rashes were common, as previously reported with CD4 mAb monotherapy. No serious infections were documented during follow-up, despite CD4+ lymphopenia in some patients. Most patients appeared to demonstrate improved RA disease control after the study. After 17–49 months after therapy, one patient was in remission, one remained off disease modifying anti-rheumatic drugs and five had stable disease, three on previously ineffective doses of methotrexate. Conclusions: We report, for the first time in man, immunotherapy with a combination of an anti-cytokine and an anti-T-cell reagent. We witnessed an unusual first-dose reaction but there were no significant infectious complications.
Author(s): Morgan AW, Hale G, Rebello PRUB, Richards SJ, Gooi H-C, Waldmann H, Emery P, Isaacs JD
Publication type: Article
Publication status: Published
Journal: QJM: An International Journal of Medicine
Year: 2008
Volume: 101
Issue: 4
Pages: 299-306
Date deposited: 12/05/2008
ISSN (print): 1460-2725
ISSN (electronic): 1460-2393
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/qjmed/hcn006
DOI: 10.1093/qjmed/hcn006
Altmetrics provided by Altmetric
