Adding ibuprofen to standard treatment for highly drug-resistant tuberculosis did not improve clinical outcomes in a pilot trial, although the anti-inflammatory drug showed signs of reducing inflammation, according to a study published in Nature Communications on July 3.
The phase IIA open-label pilot trial was conducted in Georgia and aimed to evaluate the feasibility, safety, and biological activity of adjunctive ibuprofen in adults with pre-extensively drug-resistant or extensively drug-resistant tuberculosis. The study enrolled 28 patients who all received individualized background anti-tuberculosis treatment. Half of the participants also received 400 milligrams of ibuprofen daily for two months as adjunctive therapy, while the remaining participants served as controls. Patients were followed up for six months.
Analysis indicated that two months of adjunctive ibuprofen did not increase the proportion of patients with negative sputum cultures at two months compared to controls. Both groups achieved negative sputum cultures at six-month follow-up. Radiological improvements over time were similar between groups, including primary and secondary parenchymal abnormalities, nodular lesions, and pleural abnormalities. Approximately 71% of participants in both groups were classified as cured at the end of follow-up.
Although clinical outcomes did not differ between groups, researchers observed numerically greater reductions in blood-based inflammatory mediators and transcriptomic signature scores linked to poor tuberculosis outcomes among those receiving ibuprofen. Participants treated with ibuprofen showed greater reductions in monocyte-to-lymphocyte ratio—a marker associated with disease severity—and immune mediators such as pro- and anti-inflammatory cytokines than those receiving standard care alone. However, these findings are considered exploratory due to the small sample size and baseline differences between groups.
Researchers noted that while immunomodulatory effects were observed with low-dose adjunctive ibuprofen during intensive therapy for drug-resistant tuberculosis, these effects did not translate into improved microbiological or clinical results within this pilot study period. They suggest further evaluation is needed using higher doses or alternative host-directed therapies through larger placebo-controlled trials.
