Richmond Sy

Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus

BACKGROUND & AIMS The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. METHODS A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists. RESULTS The participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. CONCLUSIONS Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease

Tumour necrosis factor (TNF)‐antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti‐drug antibodies (ADAs) may decrease their efficacy.

Vedolizumab Induction Therapy for Patients With Crohn’s Disease and Prior Anti-TNF Antagonist Failure: A Randomized, Placebo-controlled, Double-blind, Multicenter Trial: P-26

agent has not been thoroughly evaluated. A post hoc analysis evaluated this question in a 26-week randomized, double-blind, placebo-controlled trial performed in adults with moderate to severe Crohn’s disease who were stratified by corticosteroid use at baseline (PRECiSE 2 trial, NCT00152425). METHODS: Adult patients (N 1⁄4 668) with active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] 220–450) were enrolled and received open-label induction therapy with certolizumab pegol (400 mg administered subcutaneously at Weeks 0, 2, and 4). Patients who responded at Week 6 to certolizumab pegol induction therapy (the intent-to-treat [ITT] population) were randomized to continuous therapy with 400 mg certolizumab pegol or placebo every 4 weeks through Week 24, with follow-up at Week 26. While corticosteroid tapering was not mandatory, the number of patients eligible to taper corticosteroids was evaluated, along with the number of patients that initiated corticosteroid tapering between Weeks 8 and 12. Patients who, in the investigator’s opinion, showed a clinical response 8-12 weeks from their first injection of certolizumab pegol were eligible to taper corticosteroids. The decision to initiate corticosteroid tapering was at the discretion of the investigator. Corticosteroid-free clinical remission (defined as a CDAI score of 150 and discontinuation of all oral steroids) was evaluated in the certolizumab pegol arm at Week 26 using a last observation carried forward imputation. RESULTS: Among 215 patients with a response to certolizumab pegol induction therapy at Week 6 (the ITT population in the certolizumab pegol arm), 34% (74/ 215) were treated with corticosteroids at baseline. 70% (52/74) of the patients in the certolizumab pegol arm on corticosteroids at baseline were eligible to taper corticosteroid treatment. Of these eligible patients, 87% (45/52) initiated a taper of their corticosteroid treatment. 31% (14/45) of the population on corticosteroids at baseline that initiated a taper were in a corticosteroid-free clinical remission at Week 26. Additionally, 38% (82/215) of the ITT population and 49% (68/ 140) of the population not on corticosteroids at baseline were in corticosteroidfree clinical remission at Week 26. CONCLUSION(S): Approximately one third of patients on corticosteroids at baseline were able to achieve clinical remission and successfully taper corticosteroids with certolizumab pegol in the PRECiSE 2 trial. Further investigation is warranted regarding the significant proportion of patients who were able to taper off of corticosteroids while on maintenance therapy with certolizumab pegol, as well as the reasons that some patients did not initiate a corticosteroid taper when they were eligible.

P-050 High Rates of Steroid Dependence Amongst IBD Patients: Results of a Health Claims Database Analysis

BACKGROUND: Corticosteroids are effective for induction of clinical remission in inflammatory bowel disease (IBD), but are neither safe nor effective for maintenance of remission. Given their adverse effects and association with poor long-term outcomes, minimization of steroid use is a goal of therapy, and the use of steroid-sparing agents is indicated in patients that are steroid-dependent. We examined the patterns of steroid utilization within Canada. METHODS: Health claims data was purchased from IMS Brogan (including regional-private and national-private aggregate, and two different public plans). These databases do not contain ICD-9 codes and did not allow for differentiation of IBDs. As 5-ASA is a unique therapy for IBD, patients were indexed based on a claim for 5-ASA in the first month and followed for 12 consecutive months. We measured steroid utilization amongst 5-ASA claimants as follows: Fraction with ≥ 2 prednisone claims/year, fraction with a first and last prednisone claim >90 days apart, and median days elapsed between first and last prednisone claim in those with ≥ 2 prednisone claims. Utilization was characterized amongst different database types (public/private), genders, calendar years, age categories, and concomitant IBD therapies. RESULTS: The databases comprised 19,613 patients with a claim for a 5-ASA product in January 2011. The group was ∼50% male, and 70% were aged 20–65 years old. The median number of 5-ASA claims was 8/year. The patterns of steroid utilization were generally consistent between the databases (see Table 1), with little variation across database type, gender, or calendar years. However, geriatric claimants (aged >65) in the Quebec-public database had higher rates of steroid use than the other groups. Overall, 58%–73% of patients with a claim for 5-ASA and prednisone have ≥ 2 claims for prednisone. Within this group, at least half the claimants (53%–69%) had >90 days between their first and last prednisone claim, with a median time between the first and last prednisone claim ranging from 103 to 222 days. Some prednisone claimants (∼40%) also had claims for steroid-sparing therapies. After excluding those with any immunosuppressive or biologic claim, the rates of steroid dependence remained largely unchanged. DISCUSSION: Multiple treatment guidelines define steroid-dependence as: An inability to completely taper steroids within 90 days of initiation, frequent use of steroid courses (>1 course/year), and/or relapse within 3 months of stopping. The 3 measures of steroid utilization used in this analysis approximate that definition, although not without caveats. After excluding those with claims for steroid-sparing therapies, prednisone-claimants had a median of 2–4 prednisone claims per year. They also had a median time between first and last prednisone claim of at least 100 days, and more than 52% had a claim for prednisone >90 days apart. Any of these measures taken individually suggests a prevalence of steroid-dependence despite access to steroid-sparing therapies. CONCLUSIONS: The data suggest that >50% of patients on 5-ASA that are prescribed prednisone become steroid-dependent within 1 year. Steroid-sparing therapies appear underused in this group of patients, and show little change despite a shifting treatment paradigm. Table. No title available.

W1307 The Role of Argon Plasma Coagulation (APC) in the Treatment of Chronic Radiation Proctitis

Radiation proctitis is a common complication of radiation treatment for pelvic malignancies. Approximately 5 to 20 % of patients who receive radiation treatment will develop chronic complications including bleeding, fistulae and stictures. To date there are no standard recommendations for the treatment of the chronic blood loss from radiation proctitis. Studied treatments, including hyperbaric oxygen, formaldehyde, 5-ASA have had varied results. Endoscopic treatment is gaining popularity in the treatment of radiation proctitis with both APC and bipolar heater probe being studied. A number of case reports suggest APC may be useful and safe in the treatment of chronic radiation proctitis. However none have utilized a validated scoring system for treatment effect.We plan to study both the endoscopic and the clinical response of APC in the treatment of rectal bleeding from radiation proctitis. Method: Patients referred from radiation oncology with chronic blood loss from suspected radiation proctitis were approached for consent to participate in this study. The patients baseline rectal bleeding was scored using a five point bleeding scale; the patient then underwent a colonoscopy to confirm the source of bleeding. The severity of radiation proctitis was scored using a validated scoring system the rectal telangiectasia density grading score (RTG). Patients were then treated with APC and then re-evaluated in 8 weeks time. At this time, baseline bleeding score was obtained and RTG score evaluated with sigmoidoscopy. If further treatment was required the patient was again re-evaluated in 8 weeks time. Results: There were 19 patients enrolled in this study. Mean age was 72.1 (STD=8.0) and mean Hb is 134.2 g/l(STD=21.7). Three of them did not complete the study. Among the 16 patients who underwent the APC treatment, both the clinical bleeding score and RTG score were reduced after the treatment. The bleeding score reduced 0.93±1.34 (Mean ±STD), while the RTG score reduced 0.81±0.98 (Mean ±STD). The p-values for comparing the pre and post treatment bleeding and RTG scores were 0.02 and <0.01 (Wilcoxon signed ranked test) respectively. Conclusion: In this small prospective trial, APC treatment for radiation proctitis improves the clinical bleeding score and the endoscopic outcomes.

Intravenous pamidronate increases bone density in patients with Crohn's disease

CylextVlmmune Cell Function Assay was recently cleared by the FDA for the detection of cell-mediated immunity in inmmnosuppressed patients. The assay involves incubation of whole blood with phytohemaggiutinin (PHA). After the incubation, CD4 + cells are selected using magnetic particles, washed and lysed. The intracellular ATP from the selected cells is measured w~th [uciterin/lucikrase in a luminometer. If T cells have been activated, they will contain increased levels of intracdlular ATP. The amount of ATP is directly correlated with the degree of T cell activation During clinical trials on in:tmunosuppressed patients post solid organ tranplantation using this assay, three zones of reactivity were defined, expressed as ng/niL of ATP: low ( 225 and 525). Aim: In this study, pediatric patients with CD were tested to determine their CD4 immune cell iunction using the Cylex assay (discussed above) in response to 6-mercaptopurine therapy. Results: Those patients with CD either active or recalcitrant to 6-mercaptopurine therapy and requiring inlliximab therapy showed CD4 ATP levels in the high zone of reactivity. Patients whose disease was either not active or who were responding to 6-MP therapy had responses in the moderate to low range (Table). Conclusions: The Cylex TM Immune Cell Function Assay may provide clinicians with a new clinical tool to monitor their patients with CD on 6 MP therapy Future study are in progress to determine whether a therapeutic window of clinical efficacy based on the measurement of CD4 ATP levels can be developed in managing patients with CD on antimetabolite therapy.