Acetylsalicylic Acid and Ibuprofen as Adjunctive Therapy for Tuberculosis

BackgroundAs novel strategies are needed to improve tuberculosis (TB) outcomes and shorten treatment; we evaluated whether host-directed therapy with non-steroidal anti-inflammatory drugs (NSAIDs) could enhance treatment response when added to standard therapy. MethodsWe conducted a phase 2b, double-blind, placebo-controlled, randomized trial in South Africa and Georgia. Adults with microbiologically confirmed pulmonary TB were randomized to receive standard therapy plus acetylsalicylic acid (ASA) (300 mg), ibuprofen (IBU) (400 mg), or placebo twice daily for 4 weeks and once daily for 4 weeks. Primary end points were time to a 67% reduction in the clinical symptom/sign-based TB score (TBS) and time to stable sputum culture conversion (SCC). Safety and clinical, radiological and microbiological assessments were performed up to 24 weeks after treatment completion. ResultsOf 221 randomized participants, 204 were included in the analysis. No significant differences were observed in the primary end points; median time to 67% TBS reduction was 4.5 weeks (ASA) and 5.0 weeks (IBU and placebo), and median time to stable SCC was 8 weeks in all groups. Both NSAIDs were associated with earlier cavity resolution at week 8, sustained at week 24 for ASA. IBU was associated with greater clinical improvement in multidrug-resistant-TB. Adverse event rates were similar across arms. ConclusionsAdjunctive ASA and IBU did not shorten the time to clinical or microbiologic response but were associated with earlier cavity resolution and improved TBS in specific subgroups, with similar safety to standard therapy alone. Funded by the European Unions Horizon 2020; ClinicalTrials.gov number, NCT04575519.