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Concomitant Immunosuppression (concomitant + immunosuppression)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Clinical trial: cyclophosphamide pulse therapy , a promising therapeutic alternative in refractory Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009
K. J. SCHMIDT
Summary Background, In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. Aim, To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. Methods, Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2,6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). Results, Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245,550) to 100 (26,538) at week 8. Remission lasted 16 months (median, range 4,40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. Conclusions, Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD. [source]

The Success of Continued Steroid Avoidance After Kidney Transplantation in the US

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
J. D. Schold
There has been a significant increase in the use of steroid avoidance regimens as initial treatment for kidney transplant recipients. Early results of the effectiveness of this strategy has been mixed with certain prospective trials indicating increased acute rejection but population-based studies indicating similar or better graft survival as compared to steroid maintenance. We conducted a retrospective study of national registry data to evaluate risk factors for discontinuation of steroid avoidance protocols based on patient characteristics and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant recipients in the US with at least 6 months graft survival including 24 218 initially discharged without maintenance steroids. We utilized logistic models to assess risk factors for new initiation of steroids after initial steroid-avoidance and survival models to describe graft survival for patients after return to steroids. The most prominent risk factors for new initiation of steroids after deceased donor kidney transplantation included African-American race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR = 1.85, p < 0.01), elevated HLA-MM (AOR = 1.26, p < 0.01) and older donor age (AOR = 1.19, p < 0.01). Concomitant medications were also significantly associated with the propensity to newly initiate steroids. Cumulatively the study suggests that both patient characteristics and concomitant medications are strongly associated with the success of steroid avoidance immunosuppressive regimens. [source]

AZA/Tacrolimus Is Associated with Similar Outcomes as MMF/Tacrolimus among Renal Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009
J. D. Schold
There have been several retrospective studies indicating benefits associated with mycophenalate mofetil (MMF) compared to azathioprine (AZA) for renal transplant recipients. However, these analyses evaluated outcomes prior to changes in utilization patterns of concomitant immunosuppression. Recent prospective trials have indicated similar outcomes among patients treated with MMF and AZA. The aim of this study was to evaluate outcomes in a broad group of patients in the more recent era. We evaluated adult solitary renal transplant recipients from 1998 to 2006 with the national SRTR database. Primary outcomes were time to patient death and graft loss, complications and renal function. Models were adjusted for potential confounding factors, propensity scores and stratified between higher/lower risk transplants and concomitant immunosuppression. Adjusted models indicated a modest risk among AZA patients for graft loss (AHR = 1.14, 95% CI 1.07,1.20); however, this was not apparent among AZA patients also treated with tacrolimus (AHR = 0.97, 95% CI 0.85,1.11]. One-year acute rejection rates were reduced for patients on MMF versus AZA (10 vs. 13%, p < 0.01); there were no statistically significant differences of malignancies, renal function or BK virus at 1 year. The primary findings suggest the association of MMF with improved outcomes may not be apparent in patients also receiving tacrolimus. [source]

Portal Venous Donor-Specific Transfusion in Conjunction with Sirolimus Prolongs Renal Allograft Survival in Nonhuman Primates

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
K. K. Dhanireddy
Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration. [source]