Treatment Of Acute Severe Colitis Research Articles

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. We hypothesized that upadacitinib may be effective in treating acute severe colitis. A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90days of hospital discharge. One patient required re-induction with upadacitinib within 90days and no patients required change in medical therapy within 90days. Most patients who did not undergo surgery were in clinical remission within 90days and showed clinical improvement with decreased 6-point partial Mayo scores. Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

P1017 Upadacitinib as rescue therapy for the treatment of Acute Severe Colitis in an acute care setting

Abstract Background Inflammatory bowel disease is a chronic, relapsing and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy given their rapid onset of action. The aim of this study was to evaluate the efficacy of upadacitinib as an alternative rescue therapy for acute severe colitis. Methods We conducted a retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. Statistical analysis of primary and secondary endpoints was performed with descriptive analysis. Results Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Of the patients who did not undergo surgery, 63% were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores at the post-discharge visit (4.75 during admission vs. 1.25 at post discharge visit, p<0.0001). There were no adverse reactions reported in relation to upadacitinib administration during the study period. Conclusion We found that two-thirds of patients treated with upadacitinib 45mg daily for acute severe colitis were able to avoid surgery during the index admission and within 90 days post-discharge. Of the patients who were able to avoid surgery, most were able to taper steroids, did not require readmission within 90 days of index hospitalization and were in clinical remission within 90 days. Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

The Role of Tofacitinib in the Treatment of Acute Severe Colitis in Children.

Acute severe colitis (ASC) occurs in up to 15 percent of children with ulcerative colitis, with a high index of morbidity and mortality. Treatment includes high-dose steroids, infliximab, and salvage therapies. Unfortunately, up to 20 percent of patients may need an urgent colectomy due to treatment failure. We report our experience using tofacitinib for the treatment of six patients. A retrospective review of our medical electronic records was conducted. We included every patient with ASC and treatment failure, in whom tofacitinib was used as a salvage therapy. Response, complications, and disease course were noted. Six patients were included with Pediatric Ulcerative Colitis Activity Index (PUCAI) scores ranging from 65 to 85 on admission, and 35 to 85 before tofacitinib was started (P 0.07). Median response time was 72 h. A median decrease of 40 points in PUCAI was noted (P 0.00001). Mean length of stay was 18 days with discharge 9 days after tofacitinib introduction. Haemoglobin, albumin, fecal calprotectin, and CRP improved after tofacitinib (P 0.02, P 0.02, P 0.025, and P 0.01, respectively). The mean follow-up was 8.5 months, four patients achieved complete remission and only one had a recrudescence of symptoms (P 0.01). One patient had a systemic Epstein-Barr virus infection prior to tofacitinib therapy, which resolved with rituximab treatment. No other complications were noted. Tofacitinib response is rapid and impressive in children suffering from ASC, and the safety profile appears comparable to or better than other available treatments. In the future, tofacitinib should be integrated into pediatric protocols.

Quality of Life in Patients with Acute Severe Ulcerative Colitis: Long-Term Follow-Up Results from the CONSTRUCT Trial.

there is currently limited research examining the QoL of patients with Ulcerative colitis (UC) following treatment of acute severe colitis (ASUC). to examine the long-term QoL of ASUC patients enrolled in the CONSTRUCT trial following treatment of UC with infliximab or ciclosporin and to compare the differences in the QoL between the two drug treatments over time. The CONSTRUCT trial examined the cost and clinical effectiveness of infliximab and ciclosporin treatments for acute severe UC. We collected QoL questionnaire data from patients during the active trial period up to 36 months. Following trial completion, we contacted patients postannually for up to a maximum of 84 months. We collected QoL data using a disease-specific (CUCQ, or CUCQ+ for patients who had colectomy surgery) or generic (EQ5D-3L) questionnaire. We analysed QoL scores to determine if there was any difference over time and between treatments in generic or disease-specific QoL. Following initial treatment with infliximab and ciclosporin, patients experienced a statistically significant improvement in both the generic and disease-specific QoL at three months. Generic scores remained fairly static for the whole follow-up period, reducing only slightly up to 84 months. Disease-specific scores showed a much sharper improvement up to 2 years with a gradual reduction in QoL up to 84 months. Generic and disease-specific QoL remained higher than baseline values. There was no significant difference between treatments in any of the QoL scores. Both infliximab and ciclosporin improve QoL following initial treatment for ASUC. QoL scores remain higher than at admission up to 84 months post-treatment.

Clinical Experience of Use of High-dose Intravenous Methylprednisolone in Children With Acute Moderate to Severe Colitis.

Treatment of acute severe colitis (ASC) has been associated with high morbidity and high colectomy rate in children. In the prebiologics era, our centre used short-term high-dose intravenous corticosteroids (IVCS) at 2 to 30 mg · kg · day. We conducted a retrospective review to compare efficacy of different dosing regimes of IVCS. Thirty-four children treated with IVCS for ASC were included over 8 years. Patients were studied as 2 groups with similar pretreatment patient characteristics. Group 1 (standard dose) received IVCS at 2 mg · kg · day and group 2 (high dose) received IVCS at 10 to 30 mg · kg · day. Safety, efficacy, and follow-up of the entire cohort for >1 year were studied. The median IVCS dose in the standard- and high-dose cohort was 1.5 mg · kg · day (maximum 60 mg · kg · day) and 24.8 mg · kg · day (maximum 1000 mg · kg · day), respectively. Pediatric Ulcerative Colitis Activity Index scores at day 5 were significantly lower in high-dose (15, interquartile range 8.5-20) than in standard-dose IVCS (30, interquartile range 20-30). IVCS side effects were minor and reversible. Overall, medical salvage therapy was required in 5.8% (2 children) before discharge, and in 17% (6 children) at follow-up after 1 year. The colectomy rate of the entire cohort was remarkably low with 0% during admission and 11% (4 children) after 1 year, with a trend of less colectomies in high-dose (4.8%-1 child) than in standard-dose (23%-3 children). Our data show that in paediatric ASC, the short-term use of high-dose IVCS is safe and effective. Prospective studies are needed to define the role of IVCS within salvage therapy protocols.

PTU-051 Iatrogenic Hypokalaemia in Acute Severe Colitis

Introduction Intravenous corticosteroids have been established as the mainstay treatment of acute severe colitis since 1974.1 BSG and ECCO guidelines advise either IV hydrocortisone 100 mg qds or IV methylprednisolone 30 mg bd in this setting.2,3 The potent mineralocorticoid effect of hydrocortisone however is well known.4 This could predispose to hypokalaemia in this susceptible patient cohort. For this reason, we have recently changed our practice at Glasgow Royal Infirmary (GRI) to treat these patients with methylprednisolone. Methods We performed a retrospective review of electronically held records of patients who presented to GRI with acute severe colitis treated with IV hydrocortisone or methylprednisolone. We collected data on the duration of treatment, potassium level on presentation, nadir potassium level, fall in potassium level and potassium replacement per patient. Results 20 patients were treated with IV hydrocortisone for a median of 6 days, and 16 patients were treated with IV methylprednisolone for a median of 5.5 days (ns). Median serum potassium concentration on admission was 3.8 mol/l (IQR 3.4–4.1 mmol/l) in the cohort receiving hydrocortisone which was not significantly different from 4.1 mmol/l (IQR 3.7–4.1 mol/l) in the cohort receiving methylprednisolone. Following IV steroids, median nadir potassium concentration in the group receiving methylprednisolone was 3.75 mmol/l (IQR 3.5–4.1 mmol/l), not significantly different to pre-treatment values. In those receiving hydrocortisone however, potassium concentration fell by a median of 0.85 mol/l (IQR 0.2–1.1 mol/l) to a nadir of 3.1 mol/l (IQR 2.8–3.3 mol/l), significantly lower than the group receiving methylprednisolone (p Conclusion Hypokalaemia is a common occurrence in patients with acute severe colitis treated with IV hydrocortisone but is rare when methylprednisolone is used. Given that both drugs are considered to be equally effective, methylprednisolone appears to be a safer choice of corticosteroid. References 1 Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974;1:1067–1070. 2 BSG Guidelines for management IBD 2011. 3 ECCO consensus guidelines for UC 2012. 4 Ramsahoye BH, Davies SV, et al. The mineralocorticoid effects of high dose hydrocortisone. BMJ 1995;310:656. Disclosure of Interest None Declared

Do we know how to use steroids in acute severe colitis?

IntroductionOptions in the treatment of acute severe ulcerative colitis have broadened with the recognition of the value of ciclosporin and infliximab, but corticosteroids remain the first-line treatment for active ulcerative...

Long-term outcome after admission for acute severe ulcerative colitis in Oxford: The 1992–1993 cohort

To determine the long-term outcome of patients admitted with acute severe colitis (ASC) who avoided colectomy on the index admission, a retrospective cohort study was performed. Patients admitted for intensive treatment of ASC in 1992-1993 previously described for a predictive index of short-term outcome in severe ulcerative colitis (UC) were followed for a median 122 months (range 3-144). Complete responders (CR) to intensive therapy had <3 nonbloody stools/day on day 7 of the index admission; incomplete responders (IR) were all others who avoided colectomy on that admission. Main outcome measures were colectomy-free survival, time to colectomy, and duration of steroid-free remission. In all, 6/19 CR (32%) came to colectomy compared to 10/13 IR (P = 0.016; relative risk 3.33, 95% confidence interval [CI] 1.12-9.9). The median +/- interquartile range time to colectomy was 28 +/- 47 months (range 6-99) for CR who came to colectomy versus 7.5 +/- 32 (3-72) months for IR (P = 0.118). Among the IR, 7/13 came to colectomy within 12 months, and all within 6 years from the index admission. The longest period of steroid-free remission was 42 +/- 48 (0-120) months for CR, but 9 +/- 20 (1-35) months for IR (P = 0.011). One week after admission with ASC in the prebiologic era, IRs had a 50% chance of colectomy within a year and 70% within 5 years, despite cyclosporin and azathioprine where appropriate. The maximum duration of remission in CRs was almost 5 times longer than IRs. It is unknown whether biologics change the long-term outcome.