pulmicort and Proctocolitis

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Topics: Administration, Rectal; Adult; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Dosage Forms; Drug Monitoring; Female; Glucocorticoids; Humans; Male; Middle Aged; Proctocolitis; Remission Induction; Severity of Illness Index; Treatment Outcome

Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis.. Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies.. Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use.. Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423).

Topics: Administration, Oral; Administration, Rectal; Adult; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Colon, Sigmoid; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Mesalamine; Middle Aged; Proctitis; Proctocolitis; Remission Induction; Severity of Illness Index

Budesonide is a high-potency, second-generation corticosteroid designed to minimize systemic adverse consequences of conventional corticosteroids. We performed 2 randomized, phase 3 trials to evaluate the ability of budesonide rectal foam, formulated to optimize retention and provide uniform delivery of budesonide to the rectum and distal colon, to induce remission in patients with ulcerative proctitis or ulcerative proctosigmoiditis.. Two identically designed, randomized, double-blind, placebo-controlled trials evaluated the efficacy of budesonide foam for induction of remission in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis who received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo.. Remission at week 6 occurred significantly more frequently among patients receiving budesonide foam than placebo (Study 1: 38.3% vs 25.8%; P = .0324; Study 2: 44.0% vs 22.4%; P < .0001). A significantly greater percentage of patients receiving budesonide foam vs placebo achieved rectal bleeding resolution (Study 1: 46.6% vs 28.0%; P = .0022; Study 2: 50.0% vs 28.6%; P = .0002) and endoscopic improvement (Study 1: 55.6% vs 43.2%; P = .0486; Study 2: 56.0% vs 36.7%; P = .0013) at week 6. Most adverse events occurred at similar frequencies between groups, although events related to changes in cortisol values were reported more frequently with budesonide foam. There were no cases of clinically symptomatic adrenal insufficiency.. Budesonide rectal foam was well tolerated and more efficacious than placebo in inducing remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. ClinicalTrials.gov ID: NCT01008410 and NCT01008423.

Topics: Administration, Rectal; Administration, Topical; Adult; Budesonide; Colon, Sigmoid; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Proctitis; Proctocolitis; Remission Induction; Treatment Outcome; Ulcer

Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis.. To compare the therapeutic efficacy, tolerability and safety, and patient's preference of budesonide foam vs. budesonide enema.. Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) were eligible for this double-blind, double-dummy, randomized, multicentre study. They received 2 mg/25 mL budesonide foam and placebo enema (n = 265), or 2 mg/100 mL budesonide enema and placebo foam (n = 268) for 4 weeks. Primary endpoint was clinical remission (clinical activity index < or = 4) at the final/withdrawal visit (per protocol).. A total of 541 patients were randomized--533 were evaluable for intention-to-treat analysis and 449 for per protocol analysis. Clinical remission rates (per protocol) were 60% for budesonide foam and 66% for budesonide enema (P = 0.02362 for non-inferiority of foam vs. enema within a predefined non-inferiority margin of 15%). Both formulations were safe and no drug-related serious adverse events were observed. Because of better tolerability and easier application most patients preferred foam (84%).. Budesonide foam is as effective as budesonide enema in the treatment of active ulcerative proctitis or proctosigmoiditis. Both budesonide formulations are safe, and most patients prefer foam.

Topics: Administration, Rectal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Double-Blind Method; Enema; Female; Humans; Male; Middle Aged; Patient Satisfaction; Proctitis; Proctocolitis; Treatment Outcome

Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option.. To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation.. Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously.. Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h.. In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Topics: Administration, Rectal; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Colon; Female; Gamma Cameras; Humans; Male; Proctocolitis; Prospective Studies; Radionuclide Imaging; Technetium

Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema. Foam offers patients better tolerability than an enema. In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam.. Two hundred fifty-one patients with proctosigmoiditis were randomly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks.. Remission rates were comparable in the budesonide and hydrocortisone groups, 53 and 52 percent, respectively. The mean disease activity index for the two groups decreased to a similar extent, from 7.2 +/- 1.9 and 7 +/- 2 to 3.6 +/- 3.1 and 3.9 +/- 3.4 in the budesonide and hydrocortisone groups, respectively. In a subgroup of patients who had not responded to rectal administration of mesalamine, 23 of 44 (52 percent) patients who received budesonide responded favorably to the foam, as compared with 14 of 38 (37 percent) patients who received hydrocortisone (P = not significant). Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients.. This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis.

Topics: Administration, Rectal; Adult; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Dosage Forms; Female; Humans; Hydrocortisone; Male; Middle Aged; Proctocolitis

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Budesonide; Colitis, Ulcerative; Gels; Glucocorticoids; Humans; Proctocolitis

Topics: Algorithms; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Humans; Proctocolitis

Topics: Budesonide; Colon, Sigmoid; Female; Glucocorticoids; Humans; Male; Proctocolitis; Ulcer

Topics: Budesonide; Colon, Sigmoid; Female; Glucocorticoids; Humans; Male; Proctocolitis; Ulcer

Topics: Administration, Rectal; Budesonide; Colitis, Ulcerative; Enema; Humans; Hydrocortisone; Mesalamine; Patient Acceptance of Health Care; Proctocolitis; Randomized Controlled Trials as Topic