Ibuprofen shows anti-inflammatory promise in drug‑resistant TB trial

Drug-resistant tuberculosis remains one of the toughest public health problems worldwide, with some forms—pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) TB—far harder to cure. Host-directed therapies (HDTs) aim to help patients by calming harmful inflammation, limiting tissue damage, and possibly shortening treatment. Cristina Vilaplana and colleagues designed a small, pragmatic trial to test a simple and widely available candidate: ibuprofen. In a prospective, open-label, randomized pilot study (NCT02781909) carried out in Georgia, 28 adults with bacteriologically confirmed pulmonary pre-XDR or XDR-TB were enrolled and randomized 1:1. Fourteen participants received standard-of-care (SoC) TB treatment alone and 14 received SoC plus 400 mg ibuprofen daily during the first 2 months of therapy. Participants were followed for 6 months to look for early sputum culture conversion and radiological improvement as primary endpoints, with additional attention to WHO-defined final treatment outcomes, safety, health-related quality of life, and changes in inflammatory markers. The study was intended as an initial test of potential efficacy and safety rather than a definitive trial.

The trial tracked microbiological, radiological and laboratory measures. By week 2, culture negativity was observed in 27% of control participants versus 9% in the ibuprofen group (risk difference 18%, 95% CI −13 to 50). The median time to culture conversion was 4 months in both groups. At month 2, favourable X-ray evolution was seen in 64% of controls compared with 54% of the ibuprofen group (risk difference 9%, 95% CI −32 to 50), and by month 6 about 90% of participants in each arm showed radiological improvement. Final outcomes defined by WHO were comparable, with approximately 71% cured in each group, and the incidence of safety-related events did not differ significantly between groups. Importantly, the ibuprofen arm showed greater proportional reductions in inflammatory markers: a statistically significant decrease in the monocyte-to-lymphocyte ratio at months 2 and 5, reductions in interferon gamma levels, and a lower enrichment score for the Thompson_FAIL_13 gene signature at month 6, indicating a measurable anti-inflammatory effect while remaining well tolerated.

Taken together, the findings show that adjunctive ibuprofen, at 400 mg daily for the first two months, did not improve the trial’s primary microbiological or radiological endpoints in this small group of patients with pre-XDR and XDR-TB, but it was safe and produced clear anti-inflammatory changes. These results are consistent with earlier preclinical work and limited clinical reports suggesting NSAIDs can reduce harmful inflammation in TB, and they mark the first randomized trial of adjunctive ibuprofen in this patient population. The absence of a clinical benefit here may reflect baseline imbalances in disease severity, high variability between patients, or simply that a larger sample or different dosing would be required to reveal an effect on culture conversion or radiology. The authors conclude that because ibuprofen is inexpensive, well tolerated and biologically active as an immune modulator, larger studies are justified to optimize dosing, select sensitive or tailored endpoints, and identify which subgroups of patients might gain real clinical benefit from this or other HDTs.