Elisabeth Evans

Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis.

Background:Mucosal healing (MH) as a treatment target for ulcerative colitis is of growing interest because it is associated with improved clinical outcomes. However, the feasibility and probability of reaching MH in clinical practice is unknown. We therefore evaluated the feasibility of “treating to target” according to endoscopic findings to reach MH. Methods:All endoscopic outcomes of patients with ulcerative colitis followed in a single inflammatory bowel disease unit from 2011 to 2012 were reviewed and subsequent therapeutic management. Cumulative incidence of MH and histologic healing (HH) were estimated using a Kaplan–Meier method. Results:A total of 60 patients underwent at least 2 consecutive endoscopic assessments, of whom 45 and 48 patients had endoscopic and histologic evidence of active disease, respectively. After a median follow-up of 76 weeks, 27 of 45 (60%) patients with endoscopic disease activity at baseline achieved MH and 24 (50%) of 48 patients with histologic disease activity at baseline had HH. The cumulative probabilities of MH were 26%, 52%, and 70% at 26, 52, and 76 weeks, respectively. The cumulative probabilities of HH at weeks 26, 52, and 76 from the time of initial procedure were 19%, 41%, and 57%, respectively. Any adjustment in medical therapy in case of persistent endoscopic activity was associated with both MH and HH. Conclusions:Repeated assessment of endoscopic disease activity with adjustment of medical therapy to the target of MH is feasible in clinical practice in patients with ulcerative colitis, and seems to be of benefit.

Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disease of the colon; as many as 25% of patients with this disease require hospitalization. The goals of hospitalization are to assess disease severity, exclude infection, administer rapidly acting and highly effective medication regimens, and determine response. During hospitalization, patients should be given venous thromboembolism prophylaxis and monitored for the development of toxic megacolon. Patients who do not respond to intravenous corticosteroids should be considered for rescue therapy with infliximab or cyclosporine. Patients who are refractory to medical therapies or who develop toxic megacolon should be evaluated promptly for colectomy. Patients who do respond to medical therapies should be discharged on an appropriate maintenance regimen when they meet discharge criteria. We review practical evidence-based management principles and propose a day-by-day algorithm for managing patients hospitalized for ulcerative colitis.

Successful Use of Infliximab in the Treatment of Corticosteroid Dependent Collagenous Colitis

Successful Use of Infliximab in the Treatment of Corticosteroid Dependent Collagenous Colitis

High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis

Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesitys impact on clinical outcomes in biologic‐treated patients with ulcerative colitis (UC) is inconsistent.

Ustekinumab IV 6 mg/kg Loading Dose Re-induction Improves Clinical and Endoscopic Response in Crohn’s disease: A Case Series

Ustekinumab IV 6 mg/kg Loading Dose Re-induction Improves Clinical and Endoscopic Response in Crohn’s disease: A Case Series

Biomarkers Are Associated With Clinical and Endoscopic Outcomes With Vedolizumab Treatment in Ulcerative Colitis

Background Vedolizumab inhibits α4β7-mediated lymphocyte trafficking and is effective in ulcerative colitis (UC). This study evaluated drug and biomarker concentrations and patient outcomes during vedolizumab treatment in UC. Methods Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.3-37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8-35.6 weeks) outcomes were compared with serum vedolizumab concentrations, antivedolizumab antibodies, and serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects model compared biomarker trajectories over time between clinical and endoscopic remitters and nonremitters. Results Thirty-two patients were included. Soluble (s)-tumor necrosis factor (TNF)-α, s-α4β7, s-mucosal addressin cell adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with treatment. A linear mixed-effects model demonstrated that s-α4β7 (P = 0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule-1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052) decreased more rapidly in endoscopic remitters. In clinical remitters, higher week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6 ng/mL; P = 0.05) s-α4β7 were observed. In endoscopic remitters, week 2 (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P = 0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were lower. Conclusion Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-α4β7 increased, whereas s-MAdCAM-1, s-VCAM-1, s-ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points, induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas maintenance s-α4β7 concentrations were higher in remitters.

Azathioprine-induced neuro-psychiatric disorders.

Dear Sir, Neurologic and neuropsychiatric complications are uncommon in the setting of inflammatory bowel disease and even less common as a treatment adverse event. A 38 year old male presented with a ten year history of ileocolonic and perianal Crohns disease without extra-intestinal manifestation. He underwent ileocolonic resection for small bowel obstruction within the first year of diagnosis without post-operative treatment. He relapsed 7 years later. Reluctant to immunosuppressive medication, he was first treated with steroids, antibiotics as well as alternative treatments that were ineffective with occurrence of a penetrating ileo-colitis …

Successful Use of Infliximab in the Treatment of Corticosteroid Dependent Collagenous Colitis: P-3 YI

Anti-tumor necrosis factor (TNF) therapy is associated with increased infectious risk including reactivation of latent tuberculosis infection (LTBI). It is recommended that patients with risk factors for tuberculosis (TB) be evaluated for LTBI prior to initiation of anti-TNF therapy. Patients with evidence of LTBI undergo treatment before initiation of biologic therapy. The risk of disseminated TB after treatment and initiation of biologic therapy is not well characterized in patients with inflammatory bowel disease. We present a patient who developed disseminated TB as a complication of anti-TNF therapy after completing appropriate treatment for LTBI Case Report: A 52 yo Sri Lankan male with clinical and pathologic evidence of Crohn colitis is found to have asymptomatic LTBI. Treatment with isoniazid (INH) was initiated. After 6 weeks of therapy he was started on infliximab. The patient had a good initial response to therapy but required intermittent prednisone for control of his symptoms. After a viral URI, infliximab was discontinued and not restarted. He completed a 9-month course of INH and was feeling well on no anti-TB treatment. The patients Crohn disease flared and he was initiated on adalimumab after a colonoscopy confirmed active disease. Three months after adalimumab initiation and 4 months after completion of INH for LTBI he had a febrile illness, diarrhea and weight loss. A CT abdomen/pelvis was obtained and showed multiple lesions throughout the spleen and liver. The adalimumab was stopped and he was admitted to hospital for further work-up. After an extensive work-up including evaluation for fungal etiologies and a spleen biopsy he was initiated on empiric anti-TB treatment. After several weeks the AFB smear from both sputum and spleen were positive for pan-susceptible TB. While undergoing treatment for active TB he has been maintained on mesalamine based therapy with marginal control of his Crohn disease. Discussion: Prior to initiation of anti-TNF treatment patients with IBD should be evaluated for active and latent TB1. The risk of disseminated TB after treatment for LTBI and initiation of biologic therapy is unknown. If evidence of LTBI is found, treatment is recommended prior to starting biologic therapy2,3. Recommendations from the ATS and BTS vary from 1-9 months of treatment prior to starting anti-TNF therapy, even though chemoprophylaxis is only effective 70% of the time after 9 months. 4,5 We present the case of a patient with Crohn disease, found to have LTBI and initiated on therapy. After completion of LTBI treatment anti-TNF therapy was instituted. He became ill and was admitted to hospital where he was found to have disseminated TB. Though this patients TB presented after completion of therapy for LTBI most cases of disseminated TB are discovered early in the treatment course of anti-TNF therapy. Close monitoring for reactivation is warranted even if patients have undergone treatment, since treatment is not always effective. We present a case report of a patient with Crohn disease and treated LTBI who developed disseminated disease after completion of treatment and initiation of a biologic agent.