(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 Colitis

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

Tumour necrosis factor-α (TNF-α) expression may be increased in segmental colitis associated with diverticulosis (SCAD). Our aim was to assess TNF-α expression in SCAD in relationship to the treatment.. 10 patients affected by severe (type B and D) SCAD were studied (6 males, 4 females, mean age 60.54 years, range 43-85 years). All patients were treated with beclomethasone dipropionate 10 mg/day plus a probiotic preparation VSL#3 for 8 weeks. At that time, clinical, endoscopic and histological reassessment was performed. Controls were 5 patients with active ulcerative colitis (UC).. After treatment, all SCAD B and no SCAD D patients were in remission. The TNF-α expression dropped from 42.7% (+/-7.58) to 15.7% (+/-2.6) in SCAD B patients (p=0.001), and from 40% (+/-5.9) to 28.6% (+/-5.3) in SCAD D patients (p=0.005). In UC patients, the TNF-α expression dropped from 45.5% (+/-5.09) to 22.5% (+/-2.5) (p=0.001). Neither SCAD B nor SCAD D patients showed a significant difference in TNF-α expression compared to UC after treatment. Finally, TNF-α was significantly overexpressed in SCAD D than in SCAD B at the end of treatment (p=0.048).. TNF-α expression in SCAD down regulates after treatment, and seems to be related to the clinical response to therapy. This behaviour, similar to that of Inflammatory Bowel Diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

Topics: Adult; Aged; Aged, 80 and over; Beclomethasone; Biopsy; Case-Control Studies; Colitis; Colon; Colonoscopy; Combined Modality Therapy; Diverticulosis, Colonic; Down-Regulation; Female; Glucocorticoids; Humans; Italy; Male; Middle Aged; Probiotics; Remission Induction; Severity of Illness Index; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult