亚太地区结核病临床试验：应对挑战并探索解决方案

Clinical Trials in TuberculosisAcross Asia Pacific:Navigating Challenges andExploring Solutions ADELAINE LOPEZ,Associate Medical Director, Medical Science and Strategy, Asia, IQVIAARIJIT SIL,Associate Medical Director, Medical Science and Strategy, Asia, IQVIACHARU GAUTAM,Senior Medical Director, Head-ARIDV-CVM Medical Science and Strategy, Asia, IQVIA Introduction to tuberculosis disease in Asia Pacific1Global standard in the management of tuberculosis disease2Tuberculosis treatment in Asia Pacific countries3Challenges in the conduct of clinical trials in tuberculosis and potential solutions3Patient-related3Treatment-related5Health institution-and health system-related challenges6Clinical trial landscape for tuberculosis7Opportunities for clinical trial in tuberculosis in the Asia Pacific region8Key points and recommendations9Acknowledgment10Disclosures10References11About the authors16 Introduction to tuberculosis disease in Asia Pacific Tuberculosis (TB) is one of the leading causes of infectious disease related deathsin the world. It is caused by the bacterium Mycobacterium tuberculosis(M. tuberculosis) and is spread through air when a person with active TB diseasecoughs, speaks, sings, or sneezes. The lungs are the most frequent site infectedby TB bacteria, but any part of the body may be affected leading to TB disease ofa single or multiple organs.1In 2023, the World Health Organization (WHO) regionof Southeast Asia (45%) has the highest TB incident cases, followed by Africa (24%)and the Western Pacific (17%). 87% of the total global TB disease are from 30 highTB burden countries, five of these countries account for 56% of the total: India(26%), Indonesia (10%), China (6.8%), Philippines (6.8%), and Pakistan (6.3%). HighTB burden also translates to catastrophic total cost, or >20% of annual householdexpenditure or income, to the patient and the household members.2 TB disease is preventable and treatment success ratesfor drug-susceptible TB (DS-TB) remains high (at 88%) forpeople receiving the 6-month regimen. However, drug-resistant TB (DR-TB) remains a challenge and a publichealth threat. Resistance to rifampicin (RR-TB), the mosteffective first-line drug, is of high concern. Nearly halfnew MDR/RR-TB of these cases were reported from fourcountries in the Asia Pacific region: India (27% of globalcases), Indonesia (7.4%), China (7.3%) and the Philippines(7.2%). Both MDR TB and RR-TB managed with second-line drugs has a treatment success rate of 68%. Inspite of multiple drug therapies being available for TBtreatment, there is an unmet need for newer medicinesto treat drug resistant TB. Various clinical trials are beingplanned or are in progress.2 This paper will discuss the challenges in the diagnosisand management of TB disease and the conduct ofTB trials and will explore solutions to navigatethese challenges. This paper aims to provide an overview of the burdenof TB disease in Asia Pacific, and global standardof management. In 2021, a new 4-month regimen for the treatment ofdrug-susceptible TB of people 12 years of age or olderwas introduced. This regimen consisted of 17 weeksof daily isoniazid (H), rifapentine (P), and moxifloxacin(M) and eight (8) weeks of daily pyrazinamide(Z): 2HPMZ/2HPM.3The 4-month regimen is alsorecommended in the 2024 clinical practice guidelineby the American Thoracic Society (ATS), U.S. Centersfor Disease Control and Prevention (CDC), EuropeanRespiratory Society (ERS), and Infectious DiseasesSociety of America (IDSA), stating that this regimen isas efficacious and safe as the standard 6-monthregimen (2HRZE/4HR). Global standard in themanagement oftuberculosis disease The WHO consolidated guidelines on TB are consideredthe global standard and the most widely accepted TBguidelines (Table 1). Since 2010, the WHO recommendedthat drug-susceptible TB (DS-TB) be managed with a6-month regimen composed of isoniazid (H), rifampicin(R), pyrazinamide (Z), and ethambutol (E) with dailyrifampicin for 6 months: 2HRZE/4HR. Thrice-weeklydosing is not recommended in both the intensive andcontinuation phases of therapy. (World Health Organization (WHO), 2025) ATS) The USCDC/ERS/IDSA also recommended RR-TB be managedwith a 6-month course of bedaquiline, pretomanid, andlinezolid (BPaL) is if with resistance to fluoroquinoloneand a 6-month regimen of bedaquiline, pretomanid,linezolid, and moxifloxacin (BPaLM) if fluoroquinolone-susceptible. This 6-month treatment duration ispreferred over a 15-month or longer regimen.4 For MDR/RR-TB, WHO recommended 6-monthregimen bedaquiline, pretomanid, linezolid (600 mg)and moxifloxacin (BPaLM) or bedaquiline, delamanid,linezolid (600 mg), levofloxacin, and clofazimine(BDLLfxC). (Table 1) For patients with MDR/RR-TB inwhom resistance to fluoroquinolones has been excluded,WHO suggests a 9-month all-oral regimen (BLMZ,BLLfxCZ and BDLLfxZ) over longer (>18 months) regimen.Patients receiving treatment for MDR/RR-TB should bemonitored for response throug