{"doi":"10.1101/2024.01.18.24301453","title":"Effectiveness of a bedaquiline, linezolid, clofazimine “core” for multidrug-resistant tuberculosis","abstract":"Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients. Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline. Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment. Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41). Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.","journal":"medRxiv","year":2024,"id":493451,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":80984,"name":"Miguel A. 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Binegdie","orcid":"0000-0001-9722-6265","position":20,"is_corresponding":false},{"id":1340011,"name":"Kulbaram Temirova","orcid":"0009-0001-7023-2478","position":21,"is_corresponding":false},{"id":961987,"name":"Lawrence Oyewusi","orcid":null,"position":22,"is_corresponding":false},{"id":1080268,"name":"K Philippe","orcid":null,"position":23,"is_corresponding":false},{"id":325516,"name":"Stalz Charles Vilbrun","orcid":"0009-0002-9482-1725","position":24,"is_corresponding":false},{"id":961535,"name":"Uzma Khan","orcid":"0000-0002-3602-5950","position":25,"is_corresponding":false},{"id":231914,"name":"Helena Huerga","orcid":"0000-0003-0302-9063","position":26,"is_corresponding":false},{"id":376978,"name":"Molly F. 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