Purpose: The management of polypoid dysplasia in ulcerative colitis (UC) is evolving. There are at least 3 reports of polypectomy as a safe alternative to colectomy in pts with adenoma-like mass lesions (ALMs) (Rubin, et al Gastro 1999;117:1295 [n = 30]; Odze, et al Clinical Gastro Hep. 2004;2:534 [n = 24]; Kundu et al. Gastro 2005; S128(4): A579 [n = 30]). The management of high grade dysplasia (HGD) in ALMs is not well characterized. Aim of this study was to ascertain the course of pts with HGD in ALMs in the absence of any synchronous flat dysplasia. We hypothesize that colectomy is not mandated in pts after complete excision of ALMs with HGD. Methods: Pathology/clinical databases were systematically searched for dysplastic lesions in inflammatory bowel disease from 1997–2004. Pts were identified with UC who had ALM lesions, and a subset with high-grade dysplastic polyps were defined as our study cohort. Pt demographics, disease characteristics, surveillance protocol, histopathology of biopsies and colectomy specimens were evaluated. Results: 113 pts were identified with dysplastic lesions .102 (90%) of these had UC, 5(4%) had Crohn's disease and 6(6%) had indeterminate colitis. 30 of the 102 (29%) pts with UC had ALMs in the absence of synchronous flat dysplasia; of which 9(30%) had HGD in these polyps. The mean age of cohort was 61 yrs (28–75 yrs); 6/9(66%) were male. The mean duration of disease was 16.3 yrs (6–26 yrs). 7/9 (77%) pts had pancolitis .9 pts had 10 ALMs with HGD. 9/10 (90%) of these polyps were within the area of colitis. The polyps were found in: 1(10%) in cecum, 3(30%) in ascending colon, 1(10%) in descending colon, 3(30%) in sigmoid colon, and 2(20%) in rectum. Most polyps (8/10) were adenomatous and 2/10 were villous. The mean polyp size was 5.4 mm (2–12mm). 32 surveillance colonoscopies were performed (mean 3.6 colonoscopies/pt). The pts were followed for a mean of 64.5 mos (40–87 mos). 3/9 pts (33%) had colectomy. No pts in this cohort were detected to have carcinoma in surveillance biopsies and/or in their resection specimens. Conclusions: Our data suggests that the presence of high grade dysplasia in ALMs does not mandate colectomy. Continued close observation is suggested in this pt cohort after complete excision of polyps. Further prospective evaluation of this pt population is merited.
Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in 3 Phase 3, randomized, placebocontrolled studies in patients (pts) with moderate to severe UC [1]. An ongoing Phase 3, multicenter, open-label, long-term extension study (OLE; NCT01470612) included pts from OCTAVE Induction 1/2 or OCTAVE Sustain. Methods: We present an update (as of Nov 10 2017) of previous analyses of the OLE study maintenance remission subpopulation of pts in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore of 0) at Week (Wk) 52 of OCTAVE Sustain [2], who received tofacitinib 5 mg twice daily (BID) in the OLE study. Efficacy data incl. remission, mucosal healing, clinical response, and partial Mayo score (PMS) remission up to Month 24 of the OLE study (as observed and with non-responder imputation) are presented for pts in remission after receiving tofacitinib in OCTAVE Sustain. Safety data are reported for all pts who received tofacitinib 5 mg BID in the OLE study. Results: Of 944 pts who received ≥1 dose of study drug in the OLE study, 163 (mean age 45 years; 46.0% female) were in remission at Wk 52 of OCTAVE Sustain. Of these, 142 had received tofacitinib 5 mg (n=66) or 10 mg (n=76) BID in OCTAVE Sustain. 40/163 (24.5%) pts discontinued the OLE study (13 [8.0%] due to insufficient clinical response; 12 [7.4%] due to adverse events [AEs] excl. worsening UC). Binary efficacy endpoints up to Month 24 of the OLE study are shown (Table). Efficacy over 24 months was similar irrespective of tofacitinib dose previously received in OCTAVE Sustain. Among all pts receiving tofacitinib 5 mg BID in the OLE study, 78.9%, 12.0%, and 8.0% reported treatment-emergent AEs (TEAEs), serious AEs, and severe AEs, respectively. The most frequent TEAEs were nasopharyngitis and worsening of UC. 5 (2.9%) pts had serious infections and 10 (5.7%) had herpes zoster (all mild/moderate severity). Malignancy excl. non-melanoma skin cancer was reported in 1 (0.6%) pt (lung cancer). Conclusion: The majority of pts with moderate to severe UC who achieved remission after 52 wks of tofacitinib 5 or 10 mg BID in OCTAVE Sustain maintained remission, mucosal healing, clinical response, and PMS remission with tofacitinib 5 mg BID for up to 24 months in the OLE study. No new safety risks were identified.696 Figure 1 No Caption available.
Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.To report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status.We evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs).At OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs.Tofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids.http://www.gov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]).
Summary Background Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. Aims This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease. Methods Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks’ fixed, open‐label treatment. Results Sixty‐two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non‐responder imputation). Study design prevented between‐dose efficacy comparisons. Conclusions No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment.In patients who achieved a clinical response following extended induction (delayed responders), the efficacy and safety of tofacitinib were evaluated up to Month 36 of OCTAVE Open.52.2% of patients who did not achieve clinical response to 8 weeks' treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%. The safety profile of the subsequent 8 weeks was similar to the initial 8 weeks.Overall, the majority of patients achieved a clinical response after 8 or 16 weeks' induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks' induction therapy. Most delayed responders at Month 36 were in remission.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01470612.
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