Treatment of Inflammatory Bowel Disease with Biologics in Japan: A Single-Center, Retrospective Pharmacoeconomic Study.

Biologics are essential for treating inflammatory bowel disease (IBD); however, only a few studies have validated cost-effective treatment options and patient factors for biologic use using real-world data from Japanese patients with IBD. Here, we aimed to provide pharmacoeconomic evidence to support clinical decisions for IBD treatment using biologics. We assessed 183 cases (127 patients) of IBD treated with biologics between November 2004 and September 2021. Data on patient background, treatment other than biologics, treatment-related medical costs, and effectiveness index (ratio of the C-reactive protein-negative period to drug survival time) were analyzed using univariate and multivariate logistic regression analyses. Drug survival was determined using Kaplan-Meier survival curve analysis. The outcomes were to validate a novel assessment index and elucidate the following aspects using this index: the effectiveness-cost relationship of long-term biologic use in IBD and cost-effectiveness-associated patient factors. Body mass index ≥25 kg/m2 and duration of hypoalbuminemia during drug survival correlated significantly with the therapeutic effectiveness of biologics. There were no significant differences in surgical, granulocyte apheresis, or adverse-event costs per drug survival time. Biologic costs were significantly higher in the group showing lower effectiveness than in the group showing higher effectiveness. These findings hold major pharmacoeconomic implications for not only improving therapeutic outcomes through the amelioration of low albumin levels and obesity but also potentially reducing healthcare expenditure related to the use of biotherapeutics. To our knowledge, this is the first pharmacoeconomic study based on real-world data from Japanese patients with IBD receiving long-term biologic therapy.

Management of Systemic Therapies and Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma Based on Sarcopenia Assessment.

Background: Sarcopenia, defined as the loss of skeletal muscle mass (MM), physical performance, and strength, has been associated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients treated with several therapies. As systemic therapies, including molecular targeted agents, have a strong impact on sarcopenia, we aimed to review the impact of sarcopenia in patients receiving systemic therapies, especially sorafenib and hepatic arterial infusion chemotherapy (HAIC). Summary: Several studies have demonstrated that sarcopenia is associated with poor clinical outcomes in patients receiving sorafenib or lenvatinib, while HAIC has no association with overall survival (OS) and sarcopenia. Furthermore, based on our previous study, we developed the management of sorafenib score (MS score) to stratify patients' survival according to the positivity of three parameters (skeletal MM, disease control of sorafenib, and post-sorafenib therapy), ranging from 0 to 3. Patients with an MS score ≥2 (median survival time [MST], 16.4 months) showed significantly longer survival than those with an MS score ≤1 (MST, 8.4 months) (p < 0.001). This result indicates that patients need at least two positive parameters to prolong OS. Although performance status (PS) has been used in the Barcelona Clinic Liver Cancer staging system, we consider that the assessment of sarcopenia has the potential to replace PS. Key Messages: Sarcopenia is associated with poor clinical outcomes in patients of HCC receiving sorafenib or lenvatinib. The MS score, based on the positivity of three prognostic factors, including skeletal MM, in patients receiving sorafenib, can be a reliable indicator of prolonged survival.

Assessment of high-fat-diet-induced fatty liver in medaka.

Fatty liver, which has been continuously becoming more common in a number of patients, is the most common liver disease. For detailed analysis, a useful model for fatty liver is needed and fish are considered as a potential candidate. We assessed through direct observation of the liver, which is the most conventional method for non-invasive analysis of progression in fatty liver. By using transparent medaka (Oryzias latipes), we were able to observe changes in fat deposition in the liver. An analysis of the progression of fatty liver using ultrasound showed a significant increase in echo intensity, which indicates that this is a useful examination method. In addition, we clarified a metabolite profile in the medaka liver fed a high-fat diet (HFD), which had not previously been shown in detail. This medaka model, allowing non-invasive and repetitive assessment, is a useful model for the analysis of diseases that cause fatty liver in which changes in detailed metabolites are identified.

Evaluation of the "assessment for continuous treatment with hepatic arterial infusion chemotherapy" scoring system in patients with advanced hepatocellular carcinoma.

AIM: Sorafenib is the recommended standard of care for advanced hepatocellular carcinoma (HCC) patients. However, hepatic arterial infusion chemotherapy (HAIC) is a treatment option in Asia. We recently developed the assessment for continuous treatment with HAIC (ACTH) score to guide decision-making for continuous HAIC treatment. The purpose of this study was to validate the utility of the ACTH score in a dedicated cohort. METHODS: One hundred and thirty-one patients with advanced HCC were enrolled in this study (90 in the training group and 41 in the validation group). The point score (range, 0-3) was calculated as follows: Child-Pugh score before HAIC (A = 0, B = 1), α-fetoprotein (AFP) response (yes = 0, no = 1), and des-γ-carboxy prothrombin (DCP) response (yes = 0, no = 1). The AFP and DCP responses were assessed 2 weeks after HAIC induction; a positive response was defined as a reduction of ≥20% from the baseline. RESULTS: The DCP response in the validation group was significantly associated with treatment response, and the median survival time (MST) was longer in patients with an ACTH score ≤1 (15.9 months) than in those with a score ≥2 (7.0 months; P = 0.002). Survival in all patients showed significant stratification according to the ACTH score; the MSTs associated with scores of 0, 1, 2, and 3 points were 21.7, 14.4, 9.5, and 3.8 months, respectively. CONCLUSION: The ACTH score can aid in the therapeutic assessment and continued treatment planning of HCC patients receiving HAIC.

A new therapeutic assessment score for advanced hepatocellular carcinoma patients receiving hepatic arterial infusion chemotherapy.

BACKGROUND & AIMS: Hepatic arterial infusion chemotherapy (HAIC) is an option for treating advanced hepatocellular carcinoma (HCC). Because of the poor prognosis in HAIC non-responders, it is important to identify patients who may benefit from continuous HAIC treatment; however, there are currently no therapeutic assessment scores for this identification. Therefore, we aimed to establish a new therapeutic assessment score for such patients. METHODS: We retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP) and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks); a positive-response was defined as a reduction of ≥ 20% from baseline. RESULTS: Multivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007), and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH) score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤ 1 vs. ≥ 2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003). CONCLUSIONS: The ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.