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A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease.

Glucocorticoids remain the standard approach to initial systemic management of acute graft-versus-host disease (aGVHD). For patients refractory to steroids, antithymocyte globulin (ATG) is frequently used as salvage therapy. We decided to test whether the combination of corticosteroids and equine ATG would improve the outcome of initial management of aGVHD, especially in high-risk patients such as recipients of unrelated donor (URD) transplants. One hundred patients with grade II to IV aGVHD having undergone a related or URD marrow transplant were enrolled in the study. Of the patients, 46 were randomly assigned to therapy with prednisone (60 mg/m2 per day x 7 days) and 50 received ATG/prednisone (15 mg/kg ATG bid plus 20 mg/m2 prednisone bid x 5 days, each followed by an 8-week prednisone taper). An intent-to-treat analysis of the overall response at day 42 revealed equivalent complete plus partial response rates of 76% in both the prednisone and ATG/prednisone therapy groups (P > .80). In univariate analysis, patient age, donor type, site of involvement, or aGVHD stage did not influence overall response to therapy (all P > .2). When treatment arms were studied separately, no single clinical feature predicted outcome in either group. Complications were more frequent in the ATG/prednisone arm; patients experienced more infections with cytomegalovirus (44% versus 22%; P = .02) and more frequent pneumonitis, both infectious and noninfectious (50% versus 24%; P < .01). Epstein-Barr virus lymphoproliferative disease was uncommon (4 cases) and comparable in both arms (P = .35). There was no significant difference in survival at day 100, 6 months, and 2 years between the 2 treatment arms. The more intensive immunosuppressive combination of ATG/prednisone failed to improve control of aGVHD and may have affected survival by causing more infectious complications. Combination therapy with ATG should thus be reserved as second-line therapy in the management of aGVHD.

Acute Disease↗

Anti-inflammatory therapy for Alzheimer's disease: implications of the prednisone trial.

The inflammatory hypothesis of Alzheimer's disease (AD), which is supported both by basic laboratory evidence and epidemiological studies, suggests that treatment with anti-inflammatory drugs may reduce the risk or slow the progression of AD. In the first large-scale test of this hypothesis, the Alzheimer's Disease Cooperative Study (ADCS) conducted a randomized placebo-controlled trial of low-dose prednisone treatment in subjects with probable AD. There was no difference in cognitive decline between the prednisone and placebo treatment groups; subjects treated with prednisone showed behavioral decline compared to those in the placebo group. While this study indicates that a low-dose regimen of prednisone is not useful in the treatment of AD, it does not refute the inflammatory hypothesis; recent evidence supports testing of a number of alternative anti-inflammatory regimens, for prevention and/or treatment of AD. The ADCS has initiated a trial to determine whether treatment with a non-selective non-steroidal anti-inflammatory drug or a selective cyclooxygenase-2 inhibitor is effective in slowing the rate of cognitive decline in AD.

Alzheimer Disease↗

Comparison of prednisolone kinetics in patients receiving daily or alternate-day prednisone for asthma.

Prednisolone pharmacokinetics were compared in seven patients with asthma managed by alternate-day prednisone therapy and in seven patients with asthma requiring daily doses of prednisone. Steroid requirements of these patients were carefully characterized and had been stable for at least 12 months. Prednisolone volume of distribution, elimination clearance, and elimination t1/2 averaged 0.606 +/- 0.061 and 0.553 +/- 0.162 L/kg, 2.28 +/- 0.43 and 1.93 +/- 0.54 ml/min/kg, and 204 +/- 44 and 214 +/- 19 minutes in patients receiving alternate-day or daily prednisone therapy, respectively. These results indicate that differences in these pharmacokinetic parameters do not account for the well-established clinical observation that some patients require daily prednisone doses and that their disease cannot be managed with alternate-day steroid therapy.

Adult↗

Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in humans.

In healthy volunteers receiving a single intramuscular dose of 18 X 10(6) U interferon alone or after 24 hours of an 8-day course of prednisone (40 mg/day), aspirin (650 mg every 4 hours), or acetaminophen (650 mg every 4 hours), the magnitude of the biologic response to interferon was quantified by measuring the time course of the induction of 2'-5'-oligoadenylate synthetase and resistance to vesicular stomatitis virus infection in human peripheral blood mononuclear cells. Prednisone decreased the AUC of 2'-5'-oligoadenylate synthetase activity (p less than 0.05), whereas administration of aspirin or acetaminophen did not affect this biologic response. No measurable effect was seen during administration of prednisone, aspirin, or acetaminophen on the duration or intensity of vesicular stomatitis virus yield reduction. The side effects seen with interferon administration at the dose tested were not altered in a clinically meaningful manner by prednisone, aspirin, or acetaminophen.

2',5'-Oligoadenylate Synthetase↗

Altered metabolism and decreased efficacy of prednisolone and prednisone in patients with hyperthyroidism.

To evaluate the effect of hyperthyroidism on the protein binding and metabolism of prednisolone, eight subjects with hyperthyroidism were investigated before and after thyroid status returned to normal. Hyperthyroidism was associated with a reduced volume of distribution of prednisolone, a decreased systemic availability of prednisolone after oral prednisone, a displacement of the prednisolone in equilibrium with prednisone equilibrium toward prednisone, and an increased nonrenal clearance of unbound prednisolone in the presence of an impaired 6 beta-hydroxyprednisolone formation. After oral prednisone or intravenous prednisolone, patients with hyperthyroidism had lower albumin-bound, transcortin-bound, and unbound concentrations of prednisolone but normal affinities of albumin and transcortin for prednisolone binding. These differences in prednisolone plasma concentrations were biologically relevant, because the capacity of these plasma samples to inhibit allogeneically stimulated lymphocytes was lower by 70% in the hyperthyroid than in the euthyroid state. Thus hyperthyroidism reduces the biologic effect of prednisolone and exhibits a differential effect on various enzymes involved in the catabolism of prednisolone.

Administration, Oral↗

Altered skeletal muscle ultrastructure in renal transplant patients on prednisone.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. The purpose of the present investigation was to quantify in the thigh muscle the areas of the different fiber types determined by histochemical methods, and the muscle ultrastructure by means of electron microscopy, in normal subjects (N = 41) and in renal transplant patients treated with prednisone (N = 12). The cross-sectional area of all three fiber types was reduced in renal transplant patients treated with prednisone (10.6 +/- 4.3 mg/day), the fast glycolytic fibers being most affected (slow oxidative fibers: 2642 +/- 625 vs. 3677 +/- 970 micron2, P less than 0.001; fast oxidative fibers: 3275 +/- 735 vs. 4443 +/- 1343 micron2, P less than 0.01; fast glycolytic fibers: 2305 +/- 802 vs. 3920 +/- 1522 micron2, P less than 0.001). This was mostly due to a decrease in the volume of myofibrils per unit volume of muscle fiber (-30%). The intracellular lipid content and the volume density of subsarcolemmal mitochondria were increased by more than 70% in prednisone treated patients. In conclusion, the decreased myofibril areas might account for the muscle weakness in renal transplant patients treated with prednisone, and the decrease in myofibrils is in part functionally compensated by an increase in subsarcolemmal mitochondria and intracellular lipid content.

Adult↗

Antibody and pre- plus post-transplant prednisone treatments support T cell-depleted stem cell engraftment without drug-induced morbidity.

Rigorous T cell depletion methods can now be used to reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell transplantation (HSCT). However, full T cell depletion is also associated with a significant risk of graft failure. Here we hypothesize that engraftment failures after T cell-depleted HSCT may be due, in part, to the absence of GVHD prophylaxis. To test this hypothesis, we used a haploidentical mouse model to systematically measure the effects of immunosuppressive drug treatments and anti-T cell antibodies on engraftment. Results showed that engraftment was supported in all animals when hosts were pre-treated with anti-T cell antibodies, but donor chimerism was significantly improved when hosts were also treated with prednisone. Interestingly, when hosts received only pre-HSCT prednisone treatments, engraftment was not improved; when hosts received only post-HSCT prednisone (initiated near the time of irradiation), the animals became extremely ill. Results therefore demonstrated the need for both pre- and post-HSCT prednisone treatments as a means to ensure engraftment without morbidity in all host animals.

Animals↗

Adherence to asthma self-management plans with inhaled corticosteroid and oral prednisone: A descriptive analysis.

BACKGROUND: Asthma self-management plans (SMP) are widely recommended for use, but there is little information regarding the degree of patient adherence to their instructions. The aim of the present study was to perform a descriptive analysis of patient responses to worsening asthma with regard to using individualized SMP. METHODS: Diary data were obtained from an earlier 2 year study in which patients used regularly revised SMP in combination with daily recordings of peak expiratory flow (PEF) and symptoms to manage intercurrent asthma episodes. Based on PEF and symptom changes, the SMP contained instructions about increasing the dose of inhaled corticosteroid (ICS) or commencing oral prednisone during worsening asthma, depending on severity. Data from 165 patient diaries were analysed. First, documented responses to episodes of worsening asthma were matched against SMP instructions and adherence was determined using a priori criteria. Second, each occasion when the ICS dose was increased or prednisone was commenced was identified and changes in PEF and/or symptoms that may have led to these actions were sought. RESULTS: Adherence for increasing the ICS dose was dependent on asthma severity, ranging from 78% during severe episodes to 31% during mild short-lived events. When oral prednisone was indicated, patients were adherent on 56% of occasions. Symptoms prompted intervention more frequently than changes in PEF. Significant changes in PEF were absent on 41 and 48% of occasions for ICS dose increase and oral prednisone use, respectively. CONCLUSIONS: Adherence to asthma SMP is variable and often poor. It tends to increase in proportion to the severity and duration of an asthma episode. This underscores the importance of SMP in more severe asthma. Symptoms are more important then PEF in prompting patients to alter treatment. This ought to modify our approach in constructing individual asthma SMP.

Adult↗

A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.

BACKGROUND & AIMS: Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. METHODS: Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. RESULTS: Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. CONCLUSIONS: Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

Adolescent↗

Effects of deflazacort and the L-6485 metabolite on epiphyseal cartilage carbohydrate metabolism: comparison with prednisone.

Male Sprague-Dawley rats were injected with 1 mg/100 g bw/day of prednisone, 1.25 mg/1--g bw/day of deflazacort, or its metabolite, for a period of 20 days. Epiphyseal cartilage slices were incubated in a modified Krebs Ringer bicarbonate buffer, at 37 degrees C for 60 min, with either 14C-1- or 14C-6-glucose to quantitate both the absolute and relative rates of pentose shunt versus aerobic and anaerobic glycolytic activity, respectively. Measurements of both total and radioactive glucose uptake, lactate production and 14CO2 generation were expressed as either mumoles or DPM/mg cellular DNA/hr, respectively. This study demonstrated: (1) chronic prednisone administration decreased anaerobic glycolysis (glucose uptake and lactate production) 3-fold (P less than 0.01); (2) prednisone on a chronic basis produced no measured alteration in either the pentose shunt or Kreb's cycle activity; (3) both deflazacort and the deflazacort metabolite significantly stimulated (P less than 0.02) anaerobic glycolytic activity in epiphyseal cartilage tissue. In contrast to prednisone, the administration of either deflazacort or its L-6485 metabolite did not inhibit the glycolytic pathway of metabolism so necessary for epiphyseal cartilage growth and mineralization.

Aerobiosis↗

Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma.

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.

Administration, Oral↗

A controlled study of short-term prednisone treatment in adults with membranous nephropathy.

Seventy-two adults with the nephrotic syndrome without renal insufficiency had a membranous type of renal histology on biopsy. These patients were randomly allocated to at least eight weeks of alternate-day treatment with prednisone or placebo in a multicenter study. Deterioration of glomerular filtration rate was significantly more rapid in placebo-treated than in prednisone-treated patients, and ultimately 10 of 38 given placebo but only one of 34 given prednisone were in renal failure (creatinine more than 5 mg per deciliter [440 mumol per liter]) or dead (P less than 0.02). In male patients and in those with nonselective initial proteinuria, there was a trend (not reaching statistical significance) toward more rapid deterioration of renal function. Age, admission blood pressure, serum creatinine, daily total protein excretion, and severity of histologic changes did not predict the subsequent course. We conclude that a short course of alternate-day prednisone therapy was beneficial in our group of patients with idiopathic membranous nephropathy.

Adolescent↗

Resistance of long-lived lymphocytes and plasma cells in rat lymph nodes to treatment with prednisone, cyclophosphamide, 6-mercaptopurine, and actinomycin D.

The cells of the popliteal lymph nodes of rats were labeled for 4 days after a secondary immunological stimulus. 31 days after the last dose of tritiated thymidine, groups of rats were started on courses of daily, intraperitoneal injections of prednisone, cyclophosphamide, 6-mercaptopurine, or actinomycin D. The initially low doses of these agents were doubled in successive weeks until either lymphoid hypoplasia or death occurred. Rats from each group were killed weekly, and the percentages of persisting, labeled small lymphocytes in the popliteal nodes were determined. Sections of these nodes were examined for persisting, labeled plasma cells. The per cent of lymphocytes labeled increased while the total number of lymphocytes decreased during treatment with prednisone and cyclophosphamide. Prednisone decreased the numbers of long-lived plasma cells, but these cells were preferentially resistant to cyclophosphamide. Neither 6-mercaptopurine nor actinomycin D had an appreciable effect on lymphoid tissues histologically nor on the proportions of labeled, long-lived lymphocytes and plasma cells before causing the deaths of the rats receiving them. These results indicate that long-lived lymphocytes and plasma cells survive treatment with the immunolytic drugs studied, and that long-lived lymphocytes are specifically resistant to prednisone and cyclophosphamide. We believe these results have an application to the attempts to find drugs useful in the treatment of immunologic rejections of organ transplants, and for therapy of autoimmune diseases.

Animals↗

Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone.

BACKGROUND: Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear. METHODS: Thirty-three patients (14 men, 19 women) with ESRD were followed prospectively for 18 months after kidney transplantation. All patients received prednisone and cyclosporin A (CyA) with (n=18) or without azathioprine. Rejection episodes were treated with boluses of methylprednisolone. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry for the spine, hip and whole body (total, trunk, limbs) at 1, 12, 24, 36, 60 and 75 weeks after kidney transplantation. At the same time, blood was assayed for calcium, phosphorus, intact-PTH, alkaline phosphatase, creatinine and CyA, and 24-h urine was assayed for Ca and P. RESULTS: BMD at baseline was low at all skeletal sites in women, but not in men. BMD decreased significantly at the spine (-7.0+/-0.9%, week 24), trunk (-4.8+/-0.5%, week 24), total hip (-4.3+/-1.0%, week 36), whole body (-2.2+/-0.4%, week 36) and limbs (-1.0+/-0.7%, week 74). BMD changes over time followed three different patterns: no change or gain, continuous loss, and NADIR. For the spine and trunk, two thirds of patients had a NADIR pattern with recovery at the end of the study, and one-quarter of patients had continuous bone loss. For the limbs, BMD rose or remained stable (n=20), decreased continuously (n=8) or had a NADIR pattern (n=5). Neither gender nor time on dialysis prior to transplantation influenced BMD changes. Patients with PTH serum concentrations below the median value 1 week after kidney transplantation (109 pg/ml) had continuous bone loss at the whole body or limbs but not at other sites. The cumulative dose of prednisone correlated negatively with BMD changes at the spine (r=-0.39, P<0.03), hip (r=-0.50, P=0.005) and trunk (r=-0.52, P=0.002), but not at the whole body or limbs. CyA levels in blood did not correlate with BMD changes. BMD for the whole body and limbs did not change in the patients receiving azathioprine (n=16; -2.7+/-0.7%, P=0.013) but decreased in the others (-2.8+/-0.9%, P<0.0002). CONCLUSIONS: High cumulative prednisone doses are deleterious for the axial skeleton. Low levels of PTH observed 1 week after kidney transplantation are predictive of continuous cortical bone loss.

Absorptiometry, Photon↗

The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer. International (Ludwig) Breast Cancer Study Group.

BACKGROUND: The addition of low-dose prednisone (p) to the adjuvant regimen of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive a larger dose of cytotoxics when compared with those on CMF alone. However, disease-free survival and overall survival were similar for the two groups. To test the hypothesis that low-dose prednisone might influence the efficacy of the cytotoxic regimen used, the toxicity profiles of the two treatment regimens and the patterns of treatment failure (relapse, second malignancy, or death) were examined. PATIENTS AND METHODS: 491 premenopausal and perimenopausal patients with one to three positive axillary lymph nodes included in International (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and randomized to receive CMF or CMFp were analyzed for differences in long-term outcome and toxic events. The 250 patients assigned to CMF and prednisone received on the average 12% more cytotoxic drugs than those who received CMF alone. RESULTS: The 13-year DFS for the CMFp group was 49% as compared to 52% for CMF alone, and the respective OS percents were 59% and 65%. Several toxic effects such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a similar incidence in the two treatment groups. Using cumulative incidence methodology for competing risks, we detected a statistically significant increase in first relapse in the skeleton for the CMFp group at 13 years follow-up with a relative risk (RR) of 2.06 [95% confidence interval (CI), 1.23 to 3.46; P = 0.004]. Patients with larger tumors in the CMFp regimen were especially subject to this increase with a RR for failure in the skeleton of 3.32 (95% CI, 1.57 to 7.02; P = 0.0005). CMFp-treated patients also had a larger proportion of second malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P = 0.09). CONCLUSIONS: Low-dose continuous prednisone added to adjuvant CMF chemotherapy enabled the use of higher doses of cytotoxics. This increased dose had no beneficial effect on treatment outcome, but was associated with an increased risk for bone relapses and a small, not statistically significant increased incidence of second malignancies. The effects of steroids, which are widely used as antiemetics (oral or pulse injection) together with cytotoxics, should be investigated to identify their influence upon treatment outcome.

Antineoplastic Agents, Hormonal↗

Interferon-alpha, 5-FU and prednisone in metastatic renal cell carcinoma: a phase II study.

BACKGROUND: Due to the possibility of a synergistic effect between Interferon (IFN-alpha) and 5-fluorouracil (5-FU), a phase II trial was conducted in metastatic renal cell carcinoma (MRCC) combining recombinant IFN-alpha, 5-FU and prednisone. Prednisone has been shown to decrease IFN-alpha-related toxicity without reducing the response rate. PATIENTS AND METHODS: Thirty-one patients with measurable MRCC were entered into the trial; 16 of them had lung metastases only. In 26 patients (nos. 6-31) the following dose schedule was applied during an 8-week treatment cycle: IFN-alpha (Roferon, Roche, Basel, Switzerland): 12 x 10(6)U s.c. 3 times weekly; Days 1-5: 5-FU: 600 mg/m2/day continuous i.v. infusion; Weeks 3-8: 5-FU 600 mg/m2 x 1 weekly (bolus i.v.); prednisone: 10 mg x 2 per os daily for 2 weeks, and thereafter 5 mg x 2. In the first 5 patients higher doses of 5-FU led to unacceptable toxicity and subsequent dose alteration of the trial schedule. All 31 patients were evaluable for response. Seventy treatment cycles were given. RESULTS: One complete and 6 partial responses were observed (response rate: 23%, 95% CI: 10%-41%), with a median response duration of 11 months. Except in one patient, hematological toxicity was confined to grades I and II. Eight patients developed grade III oral mucositis. Adverse cardiac events were observed in 3 patients. Dose modifications of 5-FU were necessary in 16 cycles. The IFN-alpha doses were transiently reduced during 8 cycles. CONCLUSION: The assessed combination of IFN-alpha, 5-FU and prednisone is moderately active in MRCC, with response rates similar to those seen in patients on IFN-alpha monotherapy. The latter treatment approach seems preferable, as 5-FU-related toxicity (mucositis, cardiac toxicity) is averted.

Adolescent↗

Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive effect of prednisone during gut-derived sepsis.

OBJECTIVE: Corticosteroids are used broadly in clinical practice but may profoundly impair resistance to infections. In contrast, arginine and glutamine are safe and effective immunonutrients that can improve resistance to infection in both animals and humans. This study assessed whether arginine and/or glutamine, with or without dehydroepiandrosterone, a natural endogenous steroid, could reverse the susceptibility to infection caused by prednisone in a burned animal model. DESIGN: Prospective, randomized study. SETTING: A laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at the Shriners Burns Institute, Cincinnati Unit. SUBJECTS: Adult female Balb/c mice, weighing 18 to 22 g. INTERVENTIONS: Animals were prefed an arginine- and/or glutamine- or a glycine-supplemented diet for 14 days. Dehydroepiandrosterone (25 mg/kg/day) and/or prednisone (10 mg/kg/day) were given on days -4 to 0 before animals were given a gavage of 10(9) 111indium-oxine-radiolabeled or -unlabeled Escherichia coli and 20% total body surface area burn injury. Survival rate and the extent of translocation of E. coli were determined. MEASUREMENTS AND MAIN RESULTS: Feeding with diets supplemented with arginine, glutamine, and arginine plus glutamine and treatment with dehydroepiandrosterone reversed the susceptibility to infections caused by prednisone and burn injury. The beneficial effects were mediated by enhanced killing of translocated bacteria and/or by an improved gut barrier function. CONCLUSIONS: Dietary supplementation can reverse the susceptibility to infections caused by prednisone. Both arginine and glutamine as well as dehydroepiandrosterone may be useful therapeutic agents for preventing infections in steroid-treated patients.

Animals↗

Prednisone withdrawal followed by interferon alpha for treatment of chronic hepatitis C infection: results of a randomized controlled trial.

Immunosuppressive therapy increases levels of hepatitis C virus (HCV) RNA, and when combined with interferon, corticosteroids have been reported to variably improve or have no effect on sustained response rates. We conducted a randomized double-blind placebo-controlled trial in 39 patients with biopsy-proven chronic HCV infection and elevated alanine aminotransferase levels. Patients received either 6 weeks of a tapering dose of prednisone (60 ng, 40 mg, and 20 mg in 2-week intervals) or an identical placebo. All patients then received recombinant interferon alpha-2b, 3 million units three times a week for 24 weeks. Patients were then followed for a further 24 weeks. At the end of the study there was no significant difference in the sustained biochemical response rates between the two groups (4/20 vs. 3/19, p value was not significant). Prednisone-treated patients had a significant increase in HCV RNA from baseline during steroid treatment (400 +/- 60% increase vs. -280 +/- 140% decrease; p = 0.005). Two prednisone-treated patients were withdrawn from the study secondary to serious complications related to therapy. Prednisone priming before interferon alpha therapy in patients with chronic HCV infection does not improve the sustained response rate. This therapy was associated with an increase in viral burden and significant morbidity.

Adult↗