Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis.

Introduction: The present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy. Methods: We conducted two systematic reviews (protocols CRD42022308272 and CRD42022308260). We searched the PubMed, EMBASE, Web of Science, Scopus, LILACS, Virtual Health Library and Cochrane Library databases, registers of clinical trial databases and gray literature. We included clinical trials evaluating the addition of clofazimine to PB leprosy treatment and the use of clarithromycin for treating patients with rifampicin-resistant leprosy. Risk of bias (RoB) in randomized clinical trials was assessed by the RoB 2 tool and that in non-randomized clinical trials was assessed by the ROBINS-I tool; and the certainty of the evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A meta-analysis of dichotomous outcomes was performed. Results: For clofazimine, four studies were included. Cure and relapse rates were not different with the addition of clofazimine to PB leprosy treatment and demonstrated very low certainty of evidence. For clarithromycin, six studies were included. Considerable heterogeneity resulted from the difference between comparators, and studies showed no difference in the assessed outcomes with the addition of clarithromycin to rifampicin-resistant leprosy treatment. Mild adverse events were reported for both drugs but did not significantly impact treatment. Discussion: The effectiveness of both drugs still needs to be determined. Adding clofazimine to PB leprosy treatment may reduce the repercussions of an incorrect operational classification with no apparent relevant side effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308272; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308260, identifier: CRD42022308272; CRD42022308260.

Forecasting models for leprosy cases: a scoping review protocol.

INTRODUCTION: Leprosy is a neglected tropical disease caused by Mycobacterium leprae that mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract and the eyes. Mathematical models and statistical methodologies could play an important role in decision-making and help maintain the gains in elimination programmes. Various models for predicting leprosy cases have been reported in the literature, but they have different settings and distinct approaches to predicting the cases. This study describes the protocol for a scoping review to identify and synthesise information from studies using models to forecast leprosy cases. METHODS AND ANALYSIS: A scoping review methodology will be applied following the Joanna Briggs Institute methodology for scoping reviews and will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews. We will perform a systematic search from when each database started until April 2022 and we will include the following electronic databases: MEDLINE via PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Science Literature Database. Data will be extracted and recorded on a calibrated predefined data form and will be presented in a tabular form accompanied by a descriptive summary. The Prediction Model Study Risk of Bias Assessment Tool (PROBAST) will be used. ETHICS AND DISSEMINATION: No ethical approval is required for this study. This scoping review will identify and map the methodological and other characteristics of modelling studies predicting leprosy cases. We hope that the review will contribute to scientific knowledge in this area and act as a basis for researchers designing and conducting leprosy models. This information can also be used to enhance national surveillance systems and to target specific policies. The protocol and consequent publications of this scoping review will be disseminated through peer-reviewed publications and policy briefs. SYSTEMATIC REVIEW REGISTRATION: This scoping review was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/W9375).

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications.

INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

Chronic hepatitis B treatment: the cost-effectiveness of interferon compared to lamivudine.

OBJECTIVE: To perform a cost-effectiveness evaluation from the perspective of the Brazilian National Health System of alternatives strategies (i.e., conventional interferon, pegylated interferon, and lamivudine) for the treatment of patients with chronic hepatitis B who present elevated aminotransferase levels and no evidence of cirrhosis at the beginning of treatment. METHODS: A Markov model was developed for chronic hepatitis B (hepatitis B antigen e [HBeAg] positive and negative) with 40 years' time horizon. Costs and benefits were discounted at 5%. Annual rates of disease progression, costs due to complications, and the efficacy of medicines were obtained from the literature. One-way and probabilistic sensitivity analysis evaluated uncertainties. RESULTS: For HBeAg positive patients, peginterferon (48 weeks) resulted in an increase of 0.21 discounted life-years gained compared to interferon (24 weeks). The incremental cost-effectiveness ratio (ICER) converted to US dollars using the 2009 purchasing power parity conversion factor was US$100,752.24 per life-year gained. For HBeAg negative patients, it was observed that interferon (48 weeks) compared with long-term lamivudine presented an increase of 0.45 discounted life-years gained and ICER of US$15,766.90 per life-year gained. In the sensitivity analysis, the ICER was more sensitive to variation in the probability of transition from chronic hepatitis B to compensated cirrhosis, discount rate, and medicine prices. Cost-effectiveness acceptability curve for HBeAg positive (pegylated interferon vs. conventional interferon) and negative (conventional interferon vs. lamivudine) showed that conventional interferon was cost-effective until three times the gross domestic product per capita. CONCLUSIONS: For patients with chronic hepatitis B with elevated aminotransferase levels in the pretreatment and no cirrhosis who were HBeAg positive, pegylated interferon (48 weeks) provided more life-years gained when compared to conventional interferon (24 weeks), and the ICER surpasses the country's buying power, which makes conventional interferon the chosen alternative. For HBeAg negative patients, conventional interferon (48 weeks) compared to lamivudine provided more life-years gained at a favorable ICER.