Number Of Immunosuppressive Drugs Research Articles

Improved Adherence and Outcomes for Pediatric Liver Transplant Recipients by Using Text Messaging

The goal was to improve immunosuppressant adherence for pediatric patients with orthotopic liver transplants by using text messaging (TM). A prospective study of sending TM reminders to the primary medication administrator (patient or caregiver) for pediatric transplant recipients was performed. Patient records were reviewed, comparing the year before and the year of the study. The SD of serum tacrolimus levels was used as an indicator of adherence. Forty-one patients provided consent. The median age was 15 years (range: 1-27 years), and the median age at the time of transplantation was 2 years (range: 4 months to 23 years). Fourteen patients (34%) were male. In 29 of 41 cases, the medications were self-administered by the patient. The mean duration of study was 13 +/- 1.5 months. Twenty-two patients were receiving 1 immunosuppressant, 14 were receiving 2, and 5 were receiving 3. Thirteen patients (37%) stopped the study after 4 months. The mean tacrolimus level SD decreased from 3.46 microg/L before the study to 1.37 microg/L (P < .005). The number of immunosuppressants taken and patient self/caregiver medication administration did not significantly affect the results. The number of acute cellular rejection episodes decreased from 12 to 2 during the study. Risk factors for rejection were older age (17.67 vs 13.28 years) and administration of >1 immunosuppressant. We observed significant improvement in medication adherence and a reduction in rejection episodes with TM reminders for pediatric recipients of liver transplants.

Influence of age at disease onset in the outcome of paediatric systemic lupus erythematosus

The aim of this study was to investigate the influence of age at disease onset in the outcome of paediatric SLE (pSLE). Fifty-six patients with pSLE, divided into three groups (pre-pubertal, peripubertal and post-pubertal onset), were studied. The SDI (SLICC/ACR Damage Index for SLE), patients' characteristics, disease manifestations and treatments were compared using Fisher's exact test and Kruskal-Wallis test. Kaplan-Meier curves were constructed to compare the risk of damage occurrence. The risk of damage (SDI >or=1) significantly decreased when age at disease onset increased (89% in pre-pubertal pSLE, 57% in peripubertal pSLE and 38% in post-pubertal pSLE). This excess of risk was found in all disease duration intervals studied (1-3, 3-5, 5-8, 8-10, >10 years) and at the end of follow-up. Kaplan-Meier curves indicated a higher and earlier risk of damage in younger patients. Young children showed higher frequency of autoimmune family history. The frequency of neuropsychiatric disorders and damages decreased with age at disease onset (P < 0.05). Cumulative duration of high-dose prednisone (> 0.5 mg/kg/day) and number of immunosuppressive drugs used that seem to contribute to damage significantly increased when age at disease onset decreased. The risk of damage is inversely correlated with age at disease onset in pSLE. The poorer outcome observed in younger children may be explained by a more severe disease expression, may be a higher infectious susceptibility, and a more aggressive therapy, particularly within the first 6 months of disease course.

Altered adhesion molecules expression on peripheral blood mononuclear cells from patients with systemic sclerosis and clinical correlations

The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1alpha, LFA-1beta, ICAM-3, ICAM-1, and L: -selectin expressions. ICAM-3 expression was decreased while ICAM-1 was increased on SSc PBMNC, compared to controls (p = 0.04 and 0.003, respectively). A positive association was found between LFA-1alpha (r = 0.37, p = 0.03), LFA-1beta (r = 0.38, p = 0.002), ICAM-3 (r = 0.42, p = 0.01), and L-selectin (r = 0.38, p = 0.03) expressions and greater number of immunosuppressive drugs taken by SSc patients. Also, anti-centromeric positive SSc patients had lower expressions of LFA-1alpha, LFA-1beta, ICAM-3, and L-selectin. Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma.

Intravenous Immunoglobulin Therapy for Neuromuscular Disorders

Treatment of specific immune-mediated neuromuscular disorders involves consideration of many factors including severity of illness, concurrent medical problems, supportive therapies, and immune-modulating therapies. Many immune-modulating therapies are available, including steroids, an increasing number of immunosuppressive drugs, plasmapheresis, and intravenous immunoglobulin (IVIG). Deciding on which immune-modulating therapy involves selecting from those with proven efficacy for a specific disorder and global considerations of which therapies are most appropriate for an individual patient's circumstances. IVIG has become a commonly used therapy as it is well tolerated, easily administered, and is often efficacious with a relatively rapid action. IVIG has become a first-line therapy for several immune-mediated demyelinating polyneuropathies and may play a role in treating exacerbations of myasthenia gravis and selected chronic treatment-refractory cases of Lambert-Eaton myasthenic syndrome, dermatomyositis, and polymyositis.

Mycophenolate Mofetil and C-Reactive Protein in Renal Transplant Recipients

C-reactive protein (CRP) is a strong predictor of cardiovascular disease, all-cause mortality, and renal allograft loss. Little is known about the effects of immunosuppressive and cardiovascular risk-modifying drugs on CRP in renal transplant recipients. We retrospectively identified stable patients with > or =1 highly sensitive CRP measurements between January 1 and August 31, 2005. Variables collected included patient demographics; transplant, dialysis, and cardiovascular disease-related variables; and medication profiles. Univariate correlations with CRP were assessed by unpaired Student t testing, analysis of variance, or chi analysis and followed by multivariate linear regression with stepwise backward elimination until a final stable model was attained. CRP levels were obtained in 298 recipients. In univariate analysis, body mass index (P<0.0001) and systolic blood pressure (P=0.009) showed a positive correlation, whereas number of immunosuppressive drugs (P=0.05) and use of mycophenolate mofetil (MMF) (P=0.003) were negatively correlated with CRP levels. By multivariate analysis, only body mass index (P<0.0001) and MMF dose (P<0.0001) were independently and opposingly correlated with CRP. Mean CRP level was 5.18+/-5.7 mg/L in patients not taking MMF compared with 3.13+/-3.5 mg/L in those on 2000 mg per day (P=0.002). MMF use correlates inversely with CRP levels in renal transplant recipients, suggesting that immunosuppressive regime design may alter allograft and cardiovascular disease risk in these patients. Prospective study of the effects of MMF on novel cardiovascular disease risk factors such as CRP is warranted.

Pharmacodynamics in the Development of New Immunosuppressive Drugs

Over the past 10-20 years a number of immunosuppressive drugs, such as cyclosporine A, tacrolimus, sirolimus, or mycophenolate mofetil have been approved for clinical use and have been highly successful in preventing or delaying graft rejection. Nevertheless, there is an incessant need for better and safer drugs to improve short-term and long-term outcomes following transplantation. A number of low-molecular-weight molecules that interfere with immune cell functions are in development. These include molecules that inhibit the janus protein tyrosine kinase JAK3, compounds that alter lymphocyte trafficking (the sphingosine-1-phosphate receptor antagonist FTY720), and new malononitrilamides (FK778). All seem to show promising therapeutic potential. Among the biologic agents, there are high expectations for antibodies or recombinant chimeric molecules targeting costimulatory surface molecules or pathways involved in the migration of immune cells. The list of such targets includes the ligand pairs CD28:B7, CD154:CD40, LFA-1:ICAM-1, ICOS:B7RP-1, and VLA-4:VCAM-1. However, the clinical development of drugs for transplantation has proved to be difficult, complex, and time consuming. Therefore, newly emerging drug candidates will also demand better methods for monitoring their efficacy as well as their side effects in vivo. Pharmacokinetics (PK) and pharmacodynamics (PD) are complementary approaches used to select drugs on the basis of their in vivo efficacy as well as safety. Whereas PK monitors the handling of the drug by the body, PD focuses on the biologic effect of the drug on its target. Therefore, PD studies of in vivo efficacy are useful for clinical decisions to determine the optimal dose and type of immunosuppressant. At the preclinical stage, PD is aimed at accelerating the selection of lead compounds via PD-controlled trials in animals. Moreover, PD can help to discover new mechanisms of action for a drug or a drug candidate. However, its full potential has not been used, mainly because of laborious and time-consuming methodology. This review focuses on established and novel PD/PK approaches to assess immunosuppressive compounds in the context of new evolving drugs or drug combinations.

Cardiorespiratory functional assessment after pediatric heart transplantation.

Limited data are available on the exercise capacity of young heart transplant recipients. The aim of this study was therefore to assess cardiorespiratory responses to exercise in this group of patients. Fourteen consecutive heart transplant recipients (six girls and eight boys, age-range 5-15 yr) and 14 healthy matched controls underwent a Bruce treadmill test to determine: duration of test; resting and maximum heart rates; maximum systolic blood pressure; peak oxygen consumption (VO2 peak); and cardiac output. Duration of test and heart rate increase were then compared with: time since transplantation, rejections per year, and immunosuppressive drugs received. The recipients also underwent the following lung function tests: forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). When compared with healthy controls, transplant recipients had tachycardia at rest (126 +/- 3.7 beats/min; p < 0.001); significantly reduced tolerance (9.3 +/- 0.4 min; p < 0.001), a maximum heart rate of 169 +/- 5.4 beats/min (p < 0.05); a cardiac output of 5.65 +/- 0.6 L/min (p < 0.05); and a lower heart-rate increase from rest to peak exercise (p < 0.001) but a similar VO2 peak. The heart-rate increase correlated significantly with time post-transplant (r = 0.55; p < 0.05), number of rejection episodes per year (r = - 0.63; p < 0.05), and number of immunosuppressive drugs (r = - 0.60; p < 0.05). The recipients had normal FVC and FEV1 values. After surgery, few heart transplant recipients undertake physical activity, possibly owing to over-protective parents and teachers and to a lack of suitable supervised facilities. The authors stress the importance of a cardiorespiratory functional evaluation for assessment of health status and to encourage recipients, if possible, to undertake regular physical activity.

Immunosuppressive Drugs in Pregnancy

Successful pregnancies are now common in female organ transplant recipients. Despite high rates of success, pregnancy in an organ transplant recipient should be managed as a high-risk condition with emphasis on prevention and prompt treatment of rejection episodes. The number of immunosuppressive drugs and drug combinations has increased in recent years. Data accrued by a national registry indicate that pregnancy is generally successful in patients maintained on some combination of cyclosporine, azathioprine, and steroids. Relatively little information is available regarding the safety of some of the newer immunosuppressive agents in pregnancy. Until additional information is collected, transplant physicians and obstetricians must balance the efficacy of immunosuppressants in preventing allograft rejection in the mother against possible adverse drug reactions in both the mother and fetus.

The use of tacrolimus and mycophenolate mofetil after cardiac transplantation

Despite the advances in immunosuppressive therapy over the past 10 years, acute and recurrent cardiac allograft rejection remain significant problems. Although a number of immunosuppressive drugs and techniques are under development, few have progressed into clinical trials. Two novel agents, tacrolimus and mycophenolate mofetil, have recently undergone trials in liver, kidney and most recently, cardiac transplantation. Both agents are potent immunosuppressive agents, with quite different mechanisms of action and different side-effect profiles. Although the clinical trials information is currently limited, these drugs will likely play significant roles in the armamentarium of cardiac transplant immunosuppression.

Toxicity in vivo of different immunosuppressive drugs in fetal porcine pancreatic islets.

Clinical transplantation of fetal porcine islet-like cell clusters (ICC) to kidney transplanted diabetic patients has shown both morphological and biochemical evidence of prolonged xenograft survival, but no effect was seen on the insulin requirement of the transplanted patients. One possible explanation for this relative lack of success might have been the influence of the immunosuppressive drugs on the differentiation of ICC grafts. In this study, the effects of a number of immunosuppressive drugs on ICC differentiation were investigated. Normoglycemic C57BL/6 nu/nu mice were transplanted with 2x3 microliter ICC under the renal capsule. During a four-week period the animals were treated daily with azathioprine (2.0 mg/kg b.wt.), prednisolone (0.5 mg/kg b.wt.), cyclosporine (5.0 mg/kg b.wt.), cyclophosphamide (5.0 mg/kg b.wt.) 15-deoxyspergualin (5.0 mg/kg b.wt.), leflunomide (30 mg/kg b.wt.) or saline. In order to estimate rates of beta-cell DNA synthesis in the ICC grafts the mice were injected with 3H-thymidine one hour before killing and slides of the grafts were evaluated with regard to autoradiographical labeling. Other ICC grafts were evaluated by measurement of their insulin and DNA contents. Both the DNA content of ICC grafts and the beta cell labeling index in the cyclosporine animals were significantly decreased. Perfusion experiments with graft-bearing kidneys of cyclosporine-treated animals showed a significantly decreased insulin secretion in response to glucose plus theophylline. None of the other drugs influenced the differentiation of grafted ICC as evaluated in this study. Thus, it is obvious that cyclosporine inhibits both the growth and functional differentiation of transplanted ICC, which might be one reason for the relative lack of success in the clinical transplantation of porcine ICC to diabetic patients.