Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib.

AIM: Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model. METHODS: A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders. RESULTS: Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population. LIMITATIONS: Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison. CONCLUSIONS: The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Real-world assessment of SmartExam, a novel FibroScan computational method: A retrospective single-center cohort study.

BACKGROUND AND AIM: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam-equipped FibroScan for liver stiffness measurement (LSM). METHODS: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam-Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) measurements to assess its diagnostic performance. M or XL probes were selected based on the probe-to-liver capsule distance for all FibroScan examinations. RESULTS: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam-equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI-PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam-equipped FibroScan showed no significant difference. However, the SmartExam-equipped FibroScan measurement (33.6 s) took 1.4 times longer than conventional FibroScan (23.2 s). CONCLUSIONS: SmartExam has a high diagnostic performance comparable with that of conventional FibroScan. Because the results of the conventional and SmartExam-equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared with the conventional FibroScan.

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

Assessment of suitable antihypertensive therapies: Combination with high-dose amlodipine/irbesartan vs triple combination with amlodipine/irbesartan/indapamide (ASAHI-AI study).

Angiotensin receptor blockers (ARBs) plus calcium channel blockers (CCBs) are a widely used combination therapy for hypertensive patients. In order to determine which combination was better as the next-step therapy for standard-dose combination of ARBs and CCBs, a combination with high-dose CCBs or a triple combination with diuretics, the authors conducted a prospective, randomized, open-label trial to determine which of the following combination is better as the next-step treatment: a combination with high-dose CCBs or a triple combination with diuretics. Hypertensive outpatients who did not achieve their target blood pressure (BP) with usual dosages of ARBs and amlodipine 5 mg were randomly assigned to treatment with irbesartan 100 mg/amlodipine 10 mg (Group 1: n = 48) or indapamide 1 mg in addition to ARBs plus amlodipine 5 mg (Group 2: n = 46). The primary end point was changes in the systolic BP (SBP) and diastolic BP (DBP) after the 12-week treatment period, while secondary end points were changes in BP after the 24-week treatment period and laboratory values. At 12 weeks, the SBP/DBP significantly decreased from 152.1/83.4 mm Hg to 131.5/76.1 mm Hg in Group 1 and 153.9/82.1 mm Hg to 132.7/75.9 mm Hg in Group 2. Although both groups produced a similar efficacy in reducing the SBP/DBP (-19.2/-9.2 mm Hg in Group 1 and -21.6/-8.8 mm Hg in Group 2; SBP P = .378, DBP P = .825), high-dose CCBs combined with ARBs controlled hypertension without elevation of serum uric acid. These results will provide new evidence for selecting optimal combination therapies for uncontrolled hypertensive patients.

Assessment of 10-year changes in liver stiffness using vibration-controlled transient elastography in non-alcoholic fatty liver disease.

AIM: Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. METHODS: From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). RESULTS: We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). CONCLUSIONS: Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

Evaluation of the Liver Fibrosis Index calculated by using real-time tissue elastography for the non-invasive assessment of liver fibrosis in chronic liver diseases.

AIM: A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC). METHODS: Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included. They underwent transient elastography (TE), serum liver fibrosis marker testing and RTE to calculate the LF Index. RESULTS: The LF Index showed a stepwise increase with increasing histological severity of fibrosis in CHC patients (P = 0.0102), whereas no significant correlation of the LF Index with the histological severity of liver fibrosis in NAFLD patients (P = 0.852). There was a significant correlation between the LF Index and liver stiffness measured by TE in CHC patients (r = 0.319, P = 0.0009). On the other hand, no such correlation was observed in NAFLD patients. While in CHC patients, the LF Index was correlated with the FIB-4 index, no such correlation was observed in NAFLD patients. CONCLUSION: The LF Index calculated by RTE is effective for assessment of liver fibrosis in patients with CHC. On the other hand, it is not useful in patients with NAFLD. This is the first study to compare the clinical usefulness of RTE as non-invasive assessment of liver fibrosis between CHC and NAFLD. Further investigations are required to refine statistical assessment of RTE.