Steroid-dependent Crohn Research Articles

Human recombinant interleukin-10 is safe and well tolerated but does not induce remission in steroid dependent Crohn's disease

Human recombinant interleukin-10 is safe and well tolerated but does not induce remission in steroid dependent Crohn's disease

Human recombinant interleukin-10 is safe and well tolerated but does not induce remission in steroid dependent Crohn's disease

Human recombinant interleukin-10 is safe and well tolerated but does not induce remission in steroid dependent Crohn's disease

Effect of switching to budesonide on the quality of life of patients with steroid-dependent Crohn's disease

Effect of switching to budesonide on the quality of life of patients with steroid-dependent Crohn's disease

A randomized, placebo-controlled trial of an antisense ICAM-1 inhibitor (ISIS 2302) in steroid-dependent Crohn's disease showed clinical improvement at high serum levels

A randomized, placebo-controlled trial of an antisense ICAM-1 inhibitor (ISIS 2302) in steroid-dependent Crohn's disease showed clinical improvement at high serum levels

A comparison of the effect of budesonide and mesalamine on the quality of life in patients with steroid-dependent Crohn's disease

A comparison of the effect of budesonide and mesalamine on the quality of life in patients with steroid-dependent Crohn's disease

A comparison of the effect of budesonide and mesalamine on the quality of life in patients with steroid-dependent Crohn's disease

A comparison of the effect of budesonide and mesalamine on the quality of life in patients with steroid-dependent Crohn's disease

Effect of switching to budesonide on the quality of life of patients with steroid-dependent Crohn's disease

Effect of switching to budesonide on the quality of life of patients with steroid-dependent Crohn's disease

A randomized, placebo-controlled trial of an antisense ICAM-1 inhibitor (ISIS 2302) in steroid-dependent Crohn's disease showed clinical improvement at high serum levels

A randomized, placebo-controlled trial of an antisense ICAM-1 inhibitor (ISIS 2302) in steroid-dependent Crohn's disease showed clinical improvement at high serum levels

Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease

BACKGROUNDSteroid dependent patients with Crohn's disease are at high risk of developing glucocorticosteroid induced side effects.AIMSWe evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent...

Does Adjuvant Nutritional Support Diminish Steroid Dependency in Crohn Disease?

Background: Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored. Methods: Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy. Results: The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement. Conclusion: Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease.

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

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. 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. 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. 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.

Azathioprine for maintenance of remission in Crohn's disease: Benefits outweigh the risk of lymphoma

Background & Aims: Azathioprine is a commonly used and effective treatment for maintenance of remission for patients with steroid-dependent Crohn's disease (CD). However, azathioprine therapy is associated with an increased risk of non-Hodgkin's lymphoma. The objective of this analysis was to determine the impact of azathioprine therapy on survival and quality-adjusted life expectancy after accounting for both the benefits of therapy and potential increased risk of lymphoma. Methods: A decision analysis using a Markov model depicting the natural history of alternative management strategies for maintenance of remission in patients with CD was performed. Results: In the base-case analysis, treatment of CD patients with a steroid-induced remission with azathioprine resulted in an average increase in life expectancy of 0.04 years and 0.05 quality-adjusted years. The incremental gain in life expectancy decreased with increasing patient age and increasing risk of lymphoma. Conclusions: Therapy with azathioprine to preserve remission in patients with CD results in increased quality-adjusted life expectancy. This increase was greatest in young patients who have the lowest baseline risk of non-Hodgkin's lymphoma and who have the greatest life expectancy in the absence of a CD–related death. GASTROENTEROLOGY 2000;118:1018-1024

Budesonide is superior to mesalazine in maintaining disease remission for patients with steroid-dependent Crohn's disease

Budesonide is superior to mesalazine in maintaining disease remission for patients with steroid-dependent Crohn's disease

HLA-DR 8 BUT NOT IL-1RA polymorphism is associated with treatment failure of budesonide in active and steroid dependent Crohn's disease

HLA-DR 8 BUT NOT IL-1RA polymorphism is associated with treatment failure of budesonide in active and steroid dependent Crohn's disease

Budesonide is superior to mesalazine in maintaining disease remission for patients with steroiddependent Crohn's disease

Budesonide is superior to mesalazine in maintaining disease remission for patients with steroiddependent Crohn's disease

A randomized, double-blind, placebo-controlled, multi-center trial of the engineered human anti body to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroid-dependent Crohn's disease

A randomized, double-blind, placebo-controlled, multi-center trial of the engineered human anti body to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroid-dependent Crohn's disease

Double-blinded, randomized, placebo-controlled trial of the remission inducing and steroid sparing properties of two schedules of ISIS 2302 (ICAM-1 antisense) in active, steroid-dependent crohn's disease

Double-blinded, randomized, placebo-controlled trial of the remission inducing and steroid sparing properties of two schedules of ISIS 2302 (ICAM-1 antisense) in active, steroid-dependent crohn's disease

An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn's disease

Background & Aims: Thalidomide decreases production of tumor necrosis factor α, a proinflammatory cytokine associated with Crohn's disease (CD). In this study the safety, tolerance, and efficacy of low-dose thalidomide were evaluated for treatment of moderate-to-severe, steroid-dependent CD. Methods: Twelve adult male patients with Crohn's Disease Activity Index (CDAI) scores of ≥250 and ≤500 despite ≥20 mg prednisone/day were enrolled. The first 6 patients received 50 mg thalidomide every night, the next 6 received 100 mg every night. Steroid doses were stable during the first 4 weeks of treatment, then tapered during weeks 5–12. CDAI was used to assess response. Results: (1) Disease activity improved consistently in all patients during weeks 1–4: 58% response, 17% remission. (2) Clinical improvement was generally maintained despite steroid taper during weeks 5–12. All patients were able to reduce steroids by ≥50%. Forty-four percent discontinued steroids entirely. In weeks 5–12, 70% of patients responded and 20% achieved remission. (3) Side effects were mild and mostly transient, with the most common being drowsiness, peripheral neuropathy, edema, and dermatitis. Conclusions: Low-dose thalidomide appears to be well tolerated and effective over a 12-week period. Results of this pilot study support the need for controlled multicenter trials of thalidomide for treatment of CD. GASTROENTEROLOGY 1999;117:1278-1287

ISIS 2302, an antisense inhibitor of intercellular adhesion molecule 1

ISIS 2302 is a 20 base phosphorothioate oligodeoxynucleotide (ODN) that inhibits intercellular adhesion molecule 1 (ICAM-1) expression through an antisense mechanism. Murine and rat analogues have been effective at doses of 0.06 - 10 mg/kg in a spectrum of models of human inflammatory diseases and allograft transplantation, and ISIS 2302 inhibits the upregulation of ICAM-1 expression in a variety of human cells in vitro. In animals, including primates, plasma distribution half-life ranges from 30 - 60 min, but tissue elimination half-lives range from 1 - 5 days, and the compound is metabolised as other nucleic acids. In a Phase I iv. study, the pharmacokinetic behaviour of ISIS 2302 was similar to that in other primates, and single and multiple every other day doses from 0.06 - 2 mg/kg infused over 2 h were well-tolerated. Phase IIa studies have been completed in Crohn’s disease, rheumatoid arthritis, and psoriasis, and a combined Phase I/II renal allograft acute rejection prophylaxis study has just completed enrolment. In these studies, ISIS 2302, 0.5 - 2 mg/kg, or placebo was administered iv. every 2 - 3 days over 14 - 26 days (7 - 13 infusions) to 17 - 52 patients, with follow up for 6 months. In the Crohn’s study, evidence of highly durable (5+ month) remission-inducing and steroid-sparing properties were demonstrated, without clinically important adverse events. A 300-patient, pivotal quality trial investigating the steroid-sparing and remission-inducing qualities of ISIS 2302 in patients with steroid-dependent Crohn’s disease is completely enrolled, with results expected in the first half of 2000. Modest efficacy and excellent tolerability were demonstrated in the psoriasis and rheumatoid arthritis trials. A Phase IIa trial of a topical formulation in patients with psoriasis is expected to commence in late 1999, as is a trial of an enema formulation in distal ulcerative colitis. Administration by nebulisation for asthma is undergoing preclinical evaluation. Execution of future plans in organ transplantation will await the results of the ongoing Phase I/II trial.

Azathioprine: an Update on Clinical Efficacy and Safety in Inflammatory Bowel Disease

Background: The approval of azathioprine (AZA) for the long-term therapy of patients with Crohn's disease in The Netherlands. Methods: Review and update of the literature on clinical efficacy and safety of AZA in inflammatory bowel disease. Results: AZA and its metabolite 6-mercaptopurine (6-MP) are effective in the treatment of active Crohn's disease. However, the onset of the clinical response is delayed, requiring combination with other active medication in the early phase of treatment. Maintenance therapy with AZA/6-MP is also effective in the prevention of relapses in patients with Crohn's disease in remission. Indications for AZA/6-MP therapy further include refractory, fistulizing and steroid-dependent Crohn's disease. It is not known whether or when AZA/6-MP can be withdrawn in patients in long-term remission, but most clinicians discontinue therapy after 3-5 years. Although fewer data are available, AZA/6-PM appears to be effective also in the therapy of patients with ulcerative colitis. Side effects of AZA/6-MP occur in about 15% of patients and include skin rash, pancreatitis and hepatitis, dose-related neutropenia and thrombocytopenia, and risk of increased occurrence and severity of infections. Recent data suggest that the risk of malignancy, other than colorectal cancer, is not increased. Safety in pregnancy has not been studied extensively, but no increased prevalence of birth defects has been reported. Conclusions: AZA/6-MP therapy is efficacious in patients with active Crohn's disease, but the drug is especially valuable in the long-term treatment of patients with Crohn's disease and ulcerative colitis. Drug-related side effects are frequent and require discontinuation or dose-reduction of the AZA/6-MP therapy. Due to an increased risk of infections secondary to myelosuppression, careful follow-up is mandatory. Insufficient data are available on safety in pregnancy and on the risk of malignancies, but the limited data available in patients with inflammatory bowel disease appear to be reassuring.