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[Preventive treatment of rejection by the prolonged administration of OKT3: decrease of the immune response of the
A Debure1, N Chkoff, L Chatenoud
1Départment de Néphrologie, Hôpital Necker, Paris.
Abstract:
Clinical use of OKT3 for the treatment of ongoing rejection episodes has already been demonstrated as being highly effective. This work shows for the first time that combining azathioprine and OKT3 was able to delay as well as to decrease both the intensity and the quality of the anti-OKT3 immunization, allowing a 1-month prophylactic use of the MoAb. It also proves that OKT3 used prophylactically during one month can lead to 4-year first cadaver graft and patient survival rates better than those ever reported with any other immunosuppressive regimen. These results were obtained with lower doses of steroids and other immunosuppressive agents than in conventionally treated control patients. After the first two injections of OKT3, tolerance was perfect allowing out-hospital administration, and side effects consisted only in an increased number of viral infections instead of the bacterial infections observed in the conventional treatment groups. The prophylactic use of OKT3 should give even better results if it were possible to reach a 1-month administration schedule in all patients by modulating the dose of OKT3 according to the T3+ cell count and the monitoring of serum OKT3 levels.
Insights
Combining azathioprine and OKT3 (muromonab-CD3) effectively reduced anti-OKT3 immune responses. Prophylactic OKT3 use improved long-term graft survival with fewer side effects than conventional treatments.
Area of Science:
- Immunology
- Transplantation Medicine
- Pharmacology
Background:
- Clinical use of OKT3 (muromonab-CD3) is effective for treating ongoing transplant rejection.
- Anti-OKT3 immunization can limit the efficacy and duration of OKT3 treatment.
- Optimizing immunosuppressive regimens is crucial for improving graft survival rates.
Purpose of the Study:
- To investigate the combination of azathioprine and OKT3 for prophylactic use.
- To evaluate the impact of this combination on anti-OKT3 immunization.
- To assess the long-term efficacy and safety of prophylactic OKT3 in renal transplantation.
Main Methods:
- Patients received a combination of azathioprine and OKT3.
- OKT3 was administered prophylactically for one month.
- Immunogenicity, graft survival, patient survival, and side effects were monitored.
- Steroid and other immunosuppressive agent doses were compared to control groups.
Main Results:
- The combination therapy delayed and decreased the intensity and quality of anti-OKT3 immunization.
- One-month prophylactic OKT3 use resulted in superior 4-year graft and patient survival rates compared to historical controls.
- Lower doses of steroids and other immunosuppressants were used in the study group.
- Side effects shifted from bacterial to viral infections, with good tolerance allowing out-of-hospital administration.
Conclusions:
- Combining azathioprine with prophylactic OKT3 is a viable strategy to improve long-term transplant outcomes.
- Prophylactic OKT3 offers better graft and patient survival rates with a favorable safety profile.
- Further optimization of OKT3 dosing based on T3+ cell count and serum levels may enhance prophylactic efficacy.