期刊
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
卷 101, 期 4, 页码 299-306出版社
OXFORD UNIV PRESS
DOI: 10.1093/qjmed/hcn006
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资金
- MRC [G7904009] Funding Source: UKRI
- Medical Research Council [G7904009] Funding Source: researchfish
- Arthritis Research UK [18475, I0522] Funding Source: Medline
- Medical Research Council [G7904009] Funding Source: Medline
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.
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