Simulated cost-effectiveness of a novel precision-guided dosing strategy in adult patients with Crohn's disease initiating infliximab maintenance therapy.

BACKGROUND: Patients with Crohn's disease (CD) who lose response to biologics experience reduced quality of life (QoL) and costly hospitalizations. Precision-guided dosing (PGD) provides a comprehensive pharmacokinetic (PK) profile that allows for biologic dosing to be personalized. We analyzed the cost-effectiveness of infliximab (IFX) PGD relative to two other dose intensification strategies (DIS). METHODS: We developed a hybrid (Markov and decision tree) model of patients with CD who had a clinical response to IFX induction. The analysis had a US payer perspective, a base case time horizon of 5 years, and a 4-week cycle length. There were three IFX dosing comparators: PGD; dose intensification based on symptoms, inflammatory markers, and trough IFX concentration (DIS1); and dose intensification based on symptoms alone (DIS2). Patients that failed IFX initiated ustekinumab, followed by vedolizumab, and conventional therapy. Transition probabilities for IFX were estimated from real-world clinical PK data and interventional clinical trial patient-level data. All other transition probabilities were derived from published randomized clinical trials and cost-effectiveness analyses. Utility values were sourced from previous health technology assessments. Direct costs included biologic acquisition and infusion, surgeries and procedures, conventional therapy, and lab testing. The primary outcomes were incremental cost-effectiveness ratios (ICERs). The robustness of results was assessed via one-way sensitivity, scenario, and probabilistic sensitivity analyses (PSA). RESULTS: PGD was the cost-effective IFX dosing strategy with an ICER of 122,932 $ per quality-adjusted life year (QALY) relative to DIS1 and dominating DIS2. PGD had the lowest percentage (1.1%) of patients requiring a new biologic through 5 years (8.9% and 74.4% for DIS1 and DIS2, respectively). One-way sensitivity analysis demonstrated that the cost-effectiveness of PGD was most sensitive to the time between IFX doses. PSA demonstrated that joint parameter uncertainty had moderate impact on some results. CONCLUSIONS: PGD provides clinical and QoL benefits by maintaining remission and avoiding IFX failure; it is the most cost-effective under conservative assumptions.

Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Switching from intravenous to subcutaneous infliximab and vedolizumab in patients with inflammatory bowel disease: impact on trough levels, day hospital visits, and medical expenses.

OBJECTIVE: Subcutaneous (SC) infliximab (IFX) and vedolizumab (VDZ) have recently become available. We aimed to examine the impact of switching from intravenous (IV) to SC IFX and VDZ in patients with inflammatory bowel disease (IBD) on costs, the day hospital burden, trough levels, and clinical outcomes. METHODS: Our study comprised the cohort of IBD patients receiving IV IFX or VDZ at our hospital in 2022. We evaluated costs, day hospital visits, trough levels, biochemical markers, relapse rates, and self-report outcomes until Jun 30th 2023. RESULTS: Of 114 patients, 18 continued IV therapy, 80 were switched to SC therapy, and 16 were inductions. Eighty-eight (90%) remained in steroid-free remission with no difference between the IV or SC groups. The mean IFX trough level changed from 8.2 ± 4.5 µg/ml to 14.5 ± 5.9 µg/ml, p < 0.001, and the VDZ trough level from 14.7 ± 7.1 mg/ml to 26.5 ± 13.8 mg/ml, p < 0.001. The average yearly costs of infusions and injections per patient were 2 580 € and 7 482 € for IFX and 15 990 € and 13 101 € for VDZ. The annual reduction of day hospital visits was 6,9 per patient. CONCLUSIONS: IV and SC IFX and VDZ are equally effective in maintaining remission in IBD, but SC administration reduces day hospital visits and results in higher trough levels. SC VDZ is less and SC IFX more expensive than IV therapy. Further studies are needed to assess optimal dosing and separate trough levels for SC therapy.

Cost-effectiveness of intravenous vedolizumab vs subcutaneous adalimumab for moderately to severely active ulcerative colitis.

BACKGROUND: The efficacy of intravenous (IV) vedolizumab vs subcutaneous (SC) adalimumab for the treatment of moderately to severely active ulcerative colitis (UC) was assessed in the VARSITY clinical trial, which demonstrated for the first time in a head-to-head clinical trial setting the superiority of IV vedolizumab with respect to clinical remission and endoscopic improvement. Both therapies offer better clinical outcomes compared with immunomodulators and corticosteroids but are often more expensive than other pharmacologic treatment options. Thus, payers and decision makers face the task of leveraging finite resources for optimal health benefits, which can be aided by the use of cost-effectiveness models. OBJECTIVE: To assess the cost-effectiveness of IV vedolizumab vs SC adalimumab from a US payer perspective using head-to-head data from the VARSITY trial. METHODS: A cohort decision tree was developed to estimate the costs and clinical outcomes associated with IV vedolizumab vs SC adalimumab to treat adults with moderately to severely active UC. Simulated cohorts began the model at treatment induction and continued to maintenance treatment with vedolizumab or adalimumab unless experiencing nonresponse or serious adverse drug reaction (ADR), in which case those patients transitioned to second-line treatment with tofacitinib, infliximab, or golimumab, where they could achieve response and/or remission or not. Those who still did not achieve response or remission or who had a serious ADR transitioned to a state of nonresponse for the remainder of the model or received surgery. The process was modeled for patients who were treatment naive and treatment experienced at baseline separately. Efficacy and safety inputs for vedolizumab and adalimumab were taken from the VARSITY trial, and corresponding inputs for other biologics were derived from a network meta-analysis. All clinical inputs were extrapolated over 2 years. Direct medical costs (expressed in 2019 US dollars) included those related to drug acquisition and administration, ADRs, routine monitoring, and additional treatment procedures. Outcomes were not discounted given the short time horizon. Univariate sensitivity and scenario analysis were applied to evaluate the robustness of the model to underlying parameter and structural uncertainty. RESULTS: Initial treatment with vedolizumab was associated with a higher remission rate at 2 years (73.5% vs 71.5%) and higher persistence (22.0% vs 14.4%) compared with adalimumab. Total direct medical costs were lower for the vedolizumab cohort ($100,022 vs $151,133), primarily driven by the lower annual drug acquisition cost of vedolizumab ($85,953 vs $137,492). When endoscopic improvement was used as the outcome measure, IV vedolizumab was also associated with higher endoscopic remission and lower overall costs. CONCLUSIONS: With better clinical outcomes and lower direct medical costs over a 2-year model horizon, vedolizumab IV was the dominant treatment strategy vs adalimumab SC in adults with moderately to severely active UC. Outcomes were driven primarily by the probability of major ADRs and induction response. DISCLOSURES: This study was supported by Takeda Pharmaceuticals U.S.A., Inc. (Lexington, MA). Schultz and Turpin are employees of Takeda Pharmaceuticals U.S.A., Inc. Turpin has stock or stock options in Takeda Pharmaceuticals. Diakite, Carter, and Snedecor are employees of OPEN Health (Bethesda, MD), which received payment from Takeda for the design and execution of this study. This study was presented at the European Crohn's and Colitis Organisation (ECCO) 2020 Congress and Digestive Disease Week (DDW), 2020 Virtual Congress.

More Adverse Events with Home Infusions.

According to this study: Patients with immune-mediated disease who received biologic infusions at home were more likely to be admitted to the ED or hospital that day or the next compared with patients who received infusions at a facility.The safety implications of biologic home infusions need to be further evaluated.

Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II.

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.

Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study.

BACKGROUND AND AIMS: Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks. METHODS: In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks. RESULTS: In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients. CONCLUSIONS: In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.

Assessment of Vedolizumab Disease-Drug-Drug Interaction Potential in Patients With Inflammatory Bowel Diseases.

Disease-drug-drug interactions (DDDIs) have been identified in some inflammatory diseases in which elevated proinflammatory cytokines can downregulate the expression of cytochrome P450 (CYP) enzymes, potentially increasing systemic exposure to drugs metabolized by CYPs. Following anti-inflammatory treatments, CYP expression may return to normal, resulting in reduced drug exposure and diminished clinical efficacy. Vedolizumab has a well-established positive benefit-risk profile in patients with ulcerative colitis (UC) or Crohn's disease (CD) and has no known systemic immunosuppressive activity. A stepwise assessment was conducted to evaluate the DDDI potential of vedolizumab to impact exposure to drugs metabolized by CYP3A through cytokine modulation. First, a review of published data revealed that patients with UC or CD have elevated cytokine concentrations relative to healthy subjects; however, these concentrations remained below those reported to impact CYP expression. Exposure to drugs metabolized via CYP3A also appeared comparable between patients and healthy subjects. Second, serum samples from patients with UC or CD who received vedolizumab for 52 weeks were analyzed and compared with healthy subjects. Cytokine concentrations and the 4ß-hydroxycholesterol-to-cholesterol ratio, an endogenous CYP3A4 biomarker, were comparable between healthy subjects and patients both before and during vedolizumab treatment. Finally, a medical review of postmarketing DDDI cases related to vedolizumab from the past 6 years was conducted and did not show evidence of any true DDDIs. Our study demonstrated the lack of clinically meaningful effects of disease or vedolizumab treatment on the exposure to drugs metabolized via CYP3A through cytokine modulation in patients with UC or CD.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

Cost-effectiveness analysis of infliximab, adalimumab, golimumab, vedolizumab and tofacitinib for moderate to severe ulcerative colitis in Spain.

OBJECTIVE: Despite the biological drugs, the treatment of moderate to severe ulcerative colitis is still a challenge, particularly in resource-limited settings. The aim of this study was to assess the efficiency of biological drugs and tofacitinib for moderate to severe ulcerative colitis in the Spanish context. METHODS: A Markov model was built to simulate the progression of moderate to severe ulcerative colitis in a cohort of patients. The model used a time horizon of 10 years. The perspective chosen was the National Health Service, with a discount rate of 3%, and a threshold of €30,000/quality adjusted life-year (QALY). It carried out a one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS: The comparison of infliximab with adalimumab and golimumab estimated an incremental cost-effectiveness ratio (ICER) of €43,928.07/QALY and €31,340.69/QALY, with a difference of - 0.43 and - 0.82 QALY, respectively. Vedolizumab vs infliximab achieved an ICER of €122,890.19/QALY with a gain of 0.46 QALY. The comparison of infliximab with tofacitinib yielded an estimated ICER of €270,503.19/QALY, with a slight gain in QALY (0.16). The one-way sensitivity analysis showed a robust study. CONCLUSION: For a threshold of €30,000/QALY, adalimumab was the most cost-effective treatment versus infliximab for moderate to severe ulcerative colitis in Spain.

Assessment of Body Weight Changes in Patients with Inflammatory Bowel Diseases Initiating Biologic Therapy: A Prospective Cohort Study.

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS), globally affecting 11.2% of the population and imposing a direct annual cost of $1.7bn-$10bn in the US, is one of the today's major therapeutic challenges. Therefore, there is urgent need to address this issue through reviewing the tolerability and efficacy of available medications. AREAS COVERED: Over the past decade, related experiments were cited through Clinicaltrials.gov, PubMed, WHO ICTRP, and Cochrane library. Pharmacological parameters of approved medications available in the USFDA, EMA, TGA and PMDA were also stated. EXPERT OPINION: Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.

Alvimopan Is Associated With a Reduction in Length of Stay and Hospital Costs for Patients Undergoing Radical Cystectomy.

OBJECTIVE: To evaluate the impact of alvimopan in patient undergoing radical cystectomy (RC) for bladder cancer. We hypothesize that alvimopan can decrease cost for RC by reducing length of stay (LOS). METHODS: We identified patients who underwent elective RC for bladder cancer from 2009 to 2015 in the Premier Healthcare Database, a nationwide, all-payer hospital-based database, and compared patients who received and did not receive alvimopan in the perioperative period. Hospitals that had no record of administering alvimopan for patients undergoing RC were excluded. The primary outcomes were LOS and the direct hospital costs. The secondary outcomes were 90-day readmission for ileus and major complications. RESULTS: After applying the inclusion criteria, the study cohort consisted of 1087 patients with 511 patients receiving perioperative alvimopan. Alvimopan was associated with a reduction in hospital costs by -$2709 (95% confidence interval: -$4507 to -$912, P = .003), decreased median LOS (7 vs 8 days, P < .001), and lower likelihood of readmission for ileus (adjusted odds ratio: 0.63, P = .041). While alvimopan use led to higher pharmacy costs, this was outweighed by lower room and board costs due to the reduced LOS. There was no significant difference between 2 groups regarding major complications. These results were robust across multiple adjusted regression models. CONCLUSION: Our data show that alvimopan is associated with a substantial cost-saving in patients undergoing RC, and suggest that routine use of alvimopan may be a potential cost-effective strategy to reduce the overall financial burden of bladder cancer.

Practical strategy for optimizing the timing of anti-tumor necrosis factor-α therapy in Crohn disease: A nationwide population-based study.

There is little consensus on the optimal timing of anti-tumor necrosis factor (anti-TNF) therapy to decrease the rates of hospitalization and surgery in Crohn disease (CD). We aimed to assess the real-world outcomes of anti-TNF therapy and estimate the optimal timing of anti-TNF therapy in Korean patients with CD.Claims data were extracted from the Korean Health Insurance Review and Assessment Service database. Incident patients diagnosed with CD between 2009 and 2016, with at least 1 anti-TNF drug prescription, and with follow-up duration > 6 months were stratified according to the number of relapses prior to initiation of anti-TNF therapy: groups A (≤1 relapse), B (2 relapses), C (3 relapses), and D (≥4 relapses). The cumulative survival curves free from emergency hospitalization (EH) and surgery were compared across groups.Among the 2173 patients analyzed, the best and worst prognoses were noted in groups A and D, respectively. The incidences of EH and surgery decreased significantly as the use of anti-TNF agents increased. The 5-year rate of hospitalization was significantly lower in group A than in groups C and D (P = .004 and .020, respectively), but similar between groups A and B. The 5-year rate of surgery was lower in group A than in group C (P = .024), but similar among groups A, B, and D.In Asian patients with CD, anti-TNF therapy reduces the risk of EH and surgery and should be considered before three relapses, regardless of disease duration.

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy.

OBJECTIVE: To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC). METHODS: This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis. RESULTS: Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes. CONCLUSION: We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug.

Identification of the Most Cost-effective Position of Vedolizumab Among the Available Biologic Drugs for the Treatment of Ulcerative Colitis.

BACKGROUND AND AIMS: There are limited data on the most cost-effective sequencing of biologics for ulcerative colitis [UC]. METHODS: We used Markov modelling to identify the most cost-effective position for vedolizumab among biologics for steroid-dependent UC, with a base-case of a 35-year-old male. We assessed three treatment algorithms, with vedolizumab use: prior to an initial anti-tumour necrosis factor alpha [anti-TNFα] and azathioprine [Algorithm 1]; prior to a second anti-TNF and azathioprine [Algorithm 2]; and prior to colectomy [Algorithm 3]. The initial anti-TNF could be either infliximab or adalimumab. Transition probabilities, costs, and quality-adjusted life-year estimates were derived from published estimates, Medicare, and the Nationwide Inpatient Sample. Primary analyses included 100 trials of 100 000 individuals over 1 year, with a willingness-to-pay threshold of US$100,000. Multiple sensitivity analyses were conducted to assess our findings. RESULTS: From a population perspective, when both infliximab and adalimumab are available, vedolizumab was preferred as the first biologic if ≥14% of initial anti-TNF use was adalimumab. If infliximab is the primary biologic, vedolizumab use after infliximab [Algorithm 2] and prior to adalimumab was the most cost-effective strategy. All models were sensitive to biologic pricing. CONCLUSIONS: This simulation demonstrated that the most cost-effective strategy in UC depends on the proportion of patients using adalimumab as the initial anti-TNF. If adalimumab was ≥14%, vedolizumab was preferred as the first biologic. When only infliximab was available for first-line therapy, the most cost-effective position of vedolizumab was prior to cycling to adalimumab.

Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study.

Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary manifestation of cystic fibrosis. The current standard of care for CFRD involves treatment with insulin, typically via multiple daily injections. We conducted a small pilot study comparing usual care with automated glycemic control using the bihormonal (insulin and glucagon) and insulin-only configurations of the bionic pancreas. Both configurations of the bionic pancreas achieved good glycemic control, with mean glucose levels <150 mg/dl and minimal hypoglycemia. Subjects reported improved treatment satisfaction and reduced burden of diabetes management with the bionic pancreas. Further investigation of automated glycemic control in the treatment of CFRD is warranted.

Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients.

BACKGROUND AND OBJECTIVES: Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naïve patients. The present study compared endoscopic outcome in anti-TNF naïve and exposed patients, and explored if this was affected by drug exposure. METHODS: We retrospectively analysed all patients initiating vedolizumab at our tertiary referral centre since 2015. For UC, endoscopic improvement was defined as a Mayo endoscopic subscore ≤1 at week 14. For CD, endoscopic remission was defined as absence of ulcerations at week 22. Vedolizumab trough concentrations were measured at week 6, week 14 and during maintenance. RESULTS: A total of 336 patients were identified [53.3% CD], 20% of them being anti-TNF naïve. Endoscopic improvement was achieved by 56.1% of UC patients and endoscopic remission by 39.1% of CD patients. Endoscopic outcomes were significantly better in anti-TNF naïve vs exposed patients [all: 67.2% vs 42.0%, p = 0.0002; UC: 74.4% vs 50.0%, p = 0.02; CD: 57.1% vs 35.8%, p = 0.03]. Achievement of endoscopic end points significantly impacted long-term treatment continuation [p = 9.7 × 10-13]. A better endoscopic outcome was associated with significantly higher drug exposure in both CD and UC. CONCLUSIONS: The results of this observational, single-centre real-life study suggest that vedolizumab may induce endoscopic remission in both CD and UC. Although anti-TNF naïve patients had a significantly better outcome, 42% of anti-TNF exposed patients still benefited endoscopically. A clear exposure-endoscopic response relationship exists, but not all patients will benefit from treatment intensification. Hence, predictive biomarkers remain necessary. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Implementation of infliximab standardized doses after pharmacokinetic modelization in a cohort of patients with Crohn's disease.

BACKGROUND: According to infliximab (IFX) license in Crohn's disease (CD), infusion doses are based on patient's body-weight. Dose banding providing standardized doses (SD) has been implemented in parenteral chemotherapy in order to optimize aseptic unit capacity and reduce drug expenditure, duration of hospital stay and costs without decreasing efficacy. MATERIAL AND METHOD: The first part was a single-center retrospective analysis of consecutive CD patients receiving IFX maintenance therapy to determine standardized doses covering more than 50% of infusions. The second part was a prospective cohort study assessing the impact of SD compared to body-weight doses (BWD) on admission duration and costs. RESULTS: Six IFX SD covering more than 90% of infusion doses were implemented for dose banding. According to the Monte-Carlo simulation, there was no significant difference between IFX SD and BWD maintenance regimens. When assessed prospectively in 116 patients (75 patients treated with SD and 41 with BWD) corresponding to 128 infusions, hospitalization duration was shortened by 70 min per patient (p < 0.001). CONCLUSION: According to a pharmacokinetic model, IFX SD has a pharmacokinetic profile close to BWD and is associated with reduced length of hospitalization in a cohort of patients with CD. IFX SD implementation could optimize infusion units functioning and, save time and costs without decreasing efficacy.