Comparative effectiveness of three linezolid management strategies for peripheral neuropathy during multidrug- or rifampicin-resistant tuberculosis treatment.
| Title: | Comparative effectiveness of three linezolid management strategies for peripheral neuropathy during multidrug- or rifampicin-resistant tuberculosis treatment. |
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| Authors: | Romo M; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; LaHood A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Mitnick CD; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA; Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Rich ML; Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Trevisi L; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Skrahina A; National TB Control Program, Minsk, Belarus.; Oyewusi L; Ministry of Health, Maseru, Lesotho.; Bastard M; Epicentre, Paris, France.; Khan PY; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Interactive Research & Development, Singapore.; Huerga H; Epicentre, Paris, France.; Khan U; Interactive Research & Development Global, Singapore; McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montreal, QC, Canada.; Flores EH; National Hospital Arzobispo Loayza, Lima District, Peru.; Atshemyan H; National Center for Infectious Diseases, Abovyan, Armenia.; Hewison C; Médecins Sans Frontières, Paris, France.; Rashitov M; Partners In Health, Almaty, Kazakhstan.; Samieva N; Médecins Sans Frontières, Bishkek, Kyrgyzstan.; Gómez-Restrepo C; Médecins Sans Frontières, Yangon, Myanmar.; Krisnanda A; Interactive Research & Development, Jakarta, Indonesia.; Kotrikadze T; Médecins Sans Frontières, Tbilisi, Georgia.; Siraj F; National TB Control Program, Ministry of National Health Services, Regulations & Coordination, Ministry of Health of Pakistan, Karachi, Pakistan.; Khan AW; National TB Control Program, Ministry of National Health Services, Regulations & Coordination, Ministry of Health of Pakistan, Karachi, Pakistan.; Ndjeka N; National Department of Health, Pretoria, South Africa.; Adenov M; National TB Program, Kazakhstan Ministry of Health, Almaty, Kazakhstan.; Seung K; Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Kumsa A; Partners In Health, Addis Ababa, Ethiopia.; Franke MF; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA. |
| Source: | MedRxiv : the preprint server for health sciences [medRxiv] 2026 Mar 16. Date of Electronic Publication: 2026 Mar 16. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Background: Peripheral neuropathy frequently leads to linezolid dose reductions or interruptions during multidrug- or rifampicin-resistant tuberculosis treatment. The effect of these modifications to linezolid on treatment success is uncertain.; Methods: We conducted a target trial emulation using the endTB Observational Study among individuals who developed mild or moderate peripheral neuropathy while receiving linezolid 600 mg daily within 6 months of initiating an individualized regimen. We examined three linezolid management strategies: immediate change (suspension or dose reduction) during Weeks 1-7, deferred change during Weeks 8-26, and no change (i.e., continuing linezolid 600 mg daily) during Weeks 1-26. We used a clone-censor-weight approach to estimate the observational analog of the per-protocol effect on treatment success.; Results: Among 303 eligible participants from 12 countries, peripheral neuropathy occurred a median (interquartile range) of 11 (4-18) weeks after treatment initiation. Weighted, standardized probabilities of treatment success were 85.8% (95% CI: 72.7%, 93.9%) for immediate change, 78.8% (95% CI: 66.1%, 87.1%) for deferred change, and 85.2% (95% CI: 80.5%, 89.1%) for no change. Compared with no change, treatment success ratios were 1.01 for immediate change (95% CI: 0.86, 1.11) and 0.93 for deferred change (95% CI: 0.78, 1.01) strategies.; Conclusions: We did not find evidence of a substantial negative impact of immediate modification to linezolid among people who developed mild or moderate peripheral neuropathy in the first six months of an individualized regimen. Our results support the clinical practice of cautiously adjusting linezolid when needed to manage non-severe peripheral neuropathy. |
| Competing Interests: | Matthew Romo reports research funding from the National Institutes of Health with payments made to his institution. Carole D. Mitnick, Michael L. Rich, and Molly F. Franke report research funding from Unitaid, the National Institutes of Health, and Harvard Medical School Center for Global Health Delivery-Dubai with payments made to their institutions. Carole D. Mitnick also reports participation in scientific advisory boards for Akagera (one payment made to Partners In Health as an honorarium for advisory board service) and Otsuka (no payment). The remaining authors declare no potential conflicts of interest. |
| Contributed Indexing: | Keywords: Drug-Related Side Effects and Adverse Reactions; Linezolid; Multidrug-Resistant; Peripheral Nervous System Diseases; Treatment Outcome; Tuberculosis |
| Entry Date(s): | Date Created: 20260327 Date Completed: 20260413 Latest Revision: 20260413 |
| Update Code: | 20260413 |
| PubMed Central ID: | PMC13015672 |
| DOI: | 10.64898/2026.03.14.26348377 |
| PMID: | 41891020 |
| Database: | MEDLINE |
Journal Article; Preprint