Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently used immunosuppressants exacerbate cardiovascular risk. However, attempts to limit the use of these agents increase the risk of allograft rejection. Immunosuppressants targeting signal 2 and signal 3 lymphocyte activation pathways are under clinical development. Clinical data from trials of the Janus family protein tyrosine kinase-3 inhibitor tasocitinib and the costimulation blocker belatacept are presented. Additional pipeline agents are described. Results from two phase III clinical trials of belatacept revealed efficacy that is not inferior to that provided by cyclosporine (CsA). In the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial enrolling recipients of standard criteria living or deceased donor organs, the risk of rejection was higher among patients treated with a more intensive treatment regimen. Increased risk of posttransplant lymphoproliferative disorder, particularly among Epstein-Barr virus-patients, was a notable adverse event. Data from a phase II trial of tasocitinib suggested good prophylaxis of rejection. Safety signals included increased risk of infection and potential myelosuppression, leading to anemia, neutropenia, and leukopenia. Both belatacept and tasocitinib were associated with a low cardiovascular risk profile and improved renal function compared with CsA. New immunosuppressive regimens should maintain the effectiveness provided by current agents while preserving renal function and cardiovascular health. Surveillance for new adverse events must be an integral part of the long-term management strategy.
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PMID:Potential of emerging immunosuppressive strategies to improve the posttransplant cardiovascular risk profile. 2070 24

The development of new immunosuppressive drugs for kidney transplantation resulted both in better short-term outcomes and in decreased metabolic, cardiovascular, and nephrotoxicity risk. Belatacept belongs to a new class of immunosuppressive drugs that selectively inhibits T-cell activation by preventing CD28 activation and by binding its ligands B7-1 and B7-2. The result is an inactivation of costimulatory pathways. A comparative analysis of the BENEFIT and BENEFIT-EXT datasets showed belatacept regimens resulted in better cardiovascular and metabolic risk profiles than did cyclosporin A (CsA) regimens: belatacept likewise outperformed CsA in terms of lower blood pressure and serum lipids and less new onset diabetes after transplantation. About 20% of belatacept-treated patients developed adverse effects which included anemia, pyrexia, neutropenia, diarrhea, urinary tract infection, headache, and peripheral edema. At present, belatacept does not seem to predispose patients to a higher rate of infection than CsA maintenance immunosuppression. The risk of posttransplant lymphoproliferative diseases was higher in Epstein-Barr virus (EBV)-seronegative patients than in EBV-seropositive patients, but the risk may be reduced by use of a less intensive regimen and avoidance of EBV-negative patients and of patients whose pretransplant EBV serology is unknown. Belatacept provides a new option for immunosuppressive therapy in kidney transplantation, but needs further evaluation in terms of the late effects that may derive from prolonged blockage of the costimulatory system and the induction of tolerance status.
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PMID:Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. 2305 93

Regardless of recipient age at kidney transplantation (KTx), patients are at greatest risk for graft loss in adolescence, partly due to nonadherence to an oral immunosuppressive regimen. Belatacept, a non-nephrotoxic, first-in-class immunosuppressant that inhibits costimulation of T cells requires intravenous application only every 4 weeks, potentially leading to better adherence. However, it is only approved for use in adults. We report here the findings of the first study of belatacept in adolescents, comprising all patients in our department switched to belatacept post-KTx. Six patients (median age 15.5 years) were switched after a median of 7.5 months (range 23 days to 12 years), treatment range 3-28 months (cumulative 83 months): Three patients switched early (<3 months after KTx) had increased estimated glomerular filtration rate (GFR); one patient switched 12 years post-KTx has stable GFR; two patients were switched following rapid decline of and with markedly impaired GFR, changing slope in one patient. One patient had one acute rejection. In addition of two patients who received belatacept for other conditions, the only relevant adverse event was neutropenia (after a cumulative 109 months). Belatacept as primary immunosuppression is an option in Epstein-Barr virus-seropositive nonadherent adolescents if administered sufficiently early before deterioration of graft function.
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PMID:Belatacept after kidney transplantation in adolescents: a retrospective study. 2816 98