(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Diarrhea

Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis.. To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild-moderate distal ulcerative colitis.. In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate.. Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student's t-test or the Wilcoxon-Mann-Whitney test.. Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6-0.8] versus mesalazine 79% [95% confidence interval 0.6-0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7-0.9] versus mesalazine 90% [95% confidence interval 0.7-1.0]; p=n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1-0.3] versus mesalazine 28% [95% confidence interval 0.1-0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2-0.5] versus mesalazine 52% [95% confidence interval 0.3-0.6]; p=n.s.). The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p<0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p<0.001 for all three groups; T8 versus T0: p<0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p<0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0-4 versus 3, range 0-12; p<0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0-9 versus 3.5, range 0-8; p=n.s.). The safety profile was favourable for all groups.. Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis.

Topics: Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Colitis, Ulcerative; Colonoscopy; Diarrhea; Double-Blind Method; Enema; Female; Humans; Male; Mesalamine; Middle Aged; Occult Blood; Quality of Life; Severity of Illness Index; Treatment Outcome

Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesized that BD would be an effective treatment for CPI-induced colitis.. We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centers between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5 mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment.. Twenty-two patients (14 male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (common terminology criteria for adverse events, CTCAE grade diarrhea=2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo Endoscopic Score (MES) = 2) in two patients (9%), mild inflammation (MES=1) in nine patients (41%) and normal findings (MES=0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhea=0). Ten patients (45%) had symptomatic relapse on cessation of BD, half within 7 days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD.. Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomized studies are needed to confirm these findings and determine the optimum dosing regimen.

Topics: Adrenal Cortex Hormones; Beclomethasone; Colitis; Diarrhea; Humans; Immune Checkpoint Inhibitors; Inflammation; Male; Retrospective Studies