Common painkillers studied as add-ons to tuberculosis treatment

Tuberculosis remains a disease where new approaches are needed to improve outcomes and shorten the long course of treatment. Cristina Vilaplana and colleagues tested whether adding widely used non-steroidal anti-inflammatory drugs (NSAIDs) to standard therapy could help people recover faster. They ran a phase 2b, double-blind, placebo-controlled, randomized trial in South Africa and Georgia that enrolled adults with microbiologically confirmed pulmonary TB. Participants were assigned to standard therapy plus acetylsalicylic acid (ASA) 300 mg, standard therapy plus ibuprofen (IBU) 400 mg, or standard therapy plus placebo. The study drugs were given twice daily for the first four weeks and then once daily for the next four weeks. The team tracked clinical signs and symptoms using a clinical symptom/sign-based TB score (TBS) and measured bacteriologic response by time to stable sputum culture conversion (SCC). Safety, clinical, radiological, and microbiological assessments continued through 24 weeks after treatment completion to capture both short-term and longer-term effects.

A total of 221 people were randomized and 204 were included in the main analysis. The trial’s primary goals were the time it took for a 67% reduction in TBS and the time to stable SCC. The investigators found no significant differences between arms for those primary end points: the median time to a 67% reduction in TBS was 4.5 weeks for the ASA group and 5.0 weeks for both the IBU and placebo groups, while the median time to stable SCC was 8 weeks in all groups. However, both NSAIDs were linked with earlier resolution of lung cavities by week 8, and the cavity improvement with ASA was sustained at week 24. In people with multidrug-resistant-TB, IBU was associated with greater clinical improvement. Adverse event rates were similar across the ASA, IBU, and placebo arms, indicating comparable safety to standard therapy alone. The study was funded by the European Union’s Horizon 2020 and registered as ClinicalTrials.gov number NCT04575519.

The findings show a mixed picture: adding acetylsalicylic acid or ibuprofen did not shorten the main measures of clinical or microbiologic recovery in this trial, but both drugs were associated with signs of improved lung healing, notably earlier cavity resolution. The sustained cavity benefit seen with ASA at week 24 suggests there may be lasting radiological advantages even when standard outcome measures like TBS reduction and SCC are unchanged. The signal that IBU produced greater clinical improvement in people with multidrug-resistant-TB points to a possible role for targeted adjunctive use in particular subgroups. Importantly, safety did not appear worse when these NSAIDs were added to standard TB therapy. Together, these results support further investigation into whether ASA or IBU can be used as adjunctive, host-directed therapies to support lung recovery or to help specific patient groups, while recognizing they did not alter the main measures of treatment speed in this study.