REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study.

INTRODUCTION: We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC). METHODS: REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult outpatients with UC treated with tofacitinib. The primary outcomes were achievement of clinical and endoscopic remission. Safety outcomes were reported using incidence rates (events/100 patient-years of exposure). A multivariable Cox proportional hazards model was used to evaluate predictors of loss of response after tofacitinib dose de-escalation to 5 mg twice daily (BID). RESULTS: Clinical remission was achieved by 35.3% (106/300), 36.0% (104/289), and 35.2% (93/264) of patients at weeks 12, 24, and 52, respectively. Endoscopic remission was achieved by 18.5% (15/81), 23.0% (28/122), and 25.7% (35/136) of patients at weeks 12, 24, and 52, respectively. Incidence of serious infections, herpes zoster, and venous thromboembolism were 2.1 [0.9-4.2], 0.5 [0.1-1.9], and 1.1 [0.3-2.7], respectively. Among responders, 44.5% (109/245) lost response during follow-up, which was recaptured in 54.9% (39/71) of patients who re-escalated to 10 mg BID. Patients with a baseline Mayo endoscopic score of 3 (adjusted hazard ratio 3.60 [95% confidence interval: 1.70-7.62]) and prior biologic failure (adjusted hazard ratio 3.89 [95% confidence interval: 1.28-11.86]) were at a higher risk for losing response after dose reduction. DISCUSSION: One-third of patients with UC treated with tofacitinib achieved clinical remission with few serious adverse events. However, half of patients lost response with de-escalation, which was only partially recaptured with increasing the maintenance dose. Those with negative prognostic factors should be counselled about the risks and benefits of continuing high doses of tofacitinib.

Real-World Use of Azathioprine Metabolites Changes Clinical Management of Inflammatory Bowel Disease.

BACKGROUND: Thiopurines such as 6-mercaptopurine and azathioprine have complex metabolism, resulting in significant inter-individual differences in clinical efficacy and risk of drug toxicity, making conventional weight-based dosing inaccurate and potentially unsafe. Therapeutic drug monitoring (TDM) of thiopurine metabolites improves clinical outcomes through dose optimization and toxicity monitoring. Despite evidence for TDM, use is limited, due in part to test availability and awareness. The objectives of this study were twofold: (1) to investigate how thiopurine TDM impacts clinical management of IBD patients and (2) to evaluate proportion of patients outside therapeutic 6TGN levels or exhibiting signs of toxicity. METHODS: Patients who received thiopurine TDM as part of routine care underwent chart review of demographics, disease activity, medication dosing, metabolite levels, and adverse events. Changes in clinical management following TDM were measured. Additionally, we conducted a retrospective review of clinical decision making blinded and unblinded to TDM result. RESULTS: A total of 92 IBD patients were included. Levels of 6TGN were therapeutic in 29% of patients. 6TGN levels correlated weakly with weight-based dosing (r 2 = 0.057, P = 0.02). Adverse reactions were observed in 6.5%. TDM informed clinical management in 64%. Significantly more changes to clinical management occurred in those with active disease than in remission (73% versus 48%; P = 0.02) and in those on mono- versus combination therapy (48% versus 27.5%; P = 0.03). CONCLUSIONS: TDM informs clinical decision making in over two-thirds of patients. The demonstrated poor efficacy of weight-based dosing and impact of TDM on clinical management contributes to the evidence supporting the need for greater availability and uptake of thiopurine TDM.

Comparative effectiveness and cost-effectiveness analysis of a urine metabolomics test vs. alternative colorectal cancer screening strategies.

PURPOSE: Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC. METHODS: A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared. RESULTS: Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year. CONCLUSIONS: A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs.

Ustekinumab and Vedolizumab Dual Biologic Therapy in the Treatment of Crohn's Disease.

We present a case of refractory ileocolonic Crohn's disease in a 27-year-old female treated with dual ustekinumab and vedolizumab biologic therapy. She had mucosal healing for the first time in 13 years after a 10-month treatment of ustekinumab overlapped with 6 months of vedolizumab. No side effects were observed during the 6 months of dual biologic therapy. Short-term dual biologic therapy may be considered as a treatment option for induction of remission in refractory cases of Crohn's disease.

Health care resource use and costs in Crohn's disease before and after infliximab therapy.

BACKGROUND: Infliximab therapy in patients with Crohn's disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study. METHODS: A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae. RESULTS: Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (-$1,747 [P<0.05]) and fistulizing disease (-$2,530 [P<0.05]), major surgeries (-$1240 [P<0.05]) and outpatient colonoscopies (-$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.  CONCLUSION: Infliximab therapy in patients with Crohn's disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.