Could common, over-the-counter anti-inflammatory drugs become a new weapon against drug-resistant tuberculosis? Early findings suggest immunological benefits, but larger trials are needed to determine whether these lead to improved patient outcomes.
study: Adjunctive ibuprofen in highly drug-resistant and highly drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial. Image credit: George Martin Studio/Shutterstock.com
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 today. nature communications.
Can ibuprofen improve outcomes in resistant tuberculosis?
Tuberculosis (TB) is an airborne bacterial infection that primarily affects the lungs and can be transmitted from person to person. It is in the top 10 causes of death worldwide. Drug-resistant tuberculosis remains a major global public health challenge because it does not respond to antibiotics used to treat the infection.
The most effective antibiotics for tuberculosis infections include rifampicin, isoniazid, pyrazinamide, and ethambutol. However, overuse or inappropriate use of these antibiotics can lead to the emergence of drug-resistant or multidrug-resistant bacteria.
Given the increasing prevalence of multidrug-resistant or extensively drug-resistant tuberculosis, increasing disease severity, limited treatment options, and worsening disease outcomes, there is a need for the development of new treatments that suppress pathogen survival and pathogenesis by influencing host immune responses and cellular processes.
Host-directed therapies have emerged as a promising alternative to improve treatment outcomes by targeting the host’s immune system and controlling tissue damage and hyperinflammation. However, most of the drugs proposed as host-directed therapies, such as thalidomide and etanercept, have shown severe side effects in clinical trials.
Ibuprofen is a nonsteroidal anti-inflammatory drug that has been used for decades to treat pain, fever, and inflammation. In animal models of tuberculosis, the drug is expected to reduce lung injury, suppress infectious burden, and prolong survival.
Considering these preclinical advantages, currently A phase IIA open-label pilot study was designed to evaluate the feasibility, safety, and biological activity of adjuvant ibuprofen in adults with highly drug-resistant or highly drug-resistant tuberculosis in Georgia.
A total of 28 patients were enrolled in this study, all of whom received individual background antituberculosis treatment. Half of the participants received an additional 400 milligrams of ibuprofen daily as adjunctive therapy for two months, while the remaining participants received only individualized anti-tuberculosis treatment and served as controls. Patients were followed for 6 months.
Adjunctive administration of ibuprofen did not change clinical outcomes
Analysis of bacterial cultures showed that 2 months of ibuprofen treatment did not increase the proportion of patients with negative sputum cultures at 2 months, and both groups achieved negative sputum cultures at 6 months of follow-up.
Similarly, both the control and ibuprofen groups showed similar improvements over time in radiological signs such as primary and secondary parenchymal abnormalities, nodular lesions, and pleural abnormalities.
Although ibuprofen did not improve final treatment outcome, with approximately 71% of participants in both groups classified as cured at the end of follow-up, they were associated with numerically greater reductions in blood-based inflammatory mediators and transcriptome signature scores than in the control group, which were associated with poorer tuberculosis outcomes.
Why reducing inflammation did not improve outcomes
Preliminary findings from this phase IIA pilot study indicate that the addition of 2 months of ibuprofen to personalized antituberculosis therapy does not improve microbiological, radiological, or clinical outcomes compared with personalized antituberculosis therapy alone. Both treatment approaches showed similar safety and tolerability, suggesting that low-dose adjunctive ibuprofen, while feasible, did not produce measurable clinical effects during the study period.
Although these clinical outcomes were comparable, the researchers observed exploratory evidence of immunomodulatory activity in the ibuprofen-treated group. Compared to the standard treatment group, participants who received ibuprofen showed a numerically greater reduction in the monocyte-to-lymphocyte ratio, a marker that has previously been associated with the severity of tuberculosis. This finding suggests that ibuprofen may influence inflammatory pathways involved in disease progression and supports further investigation of this drug as a host-directed therapy.
This pattern extended to circulating immune mediators, with participants treated with ibuprofen showing numerically greater reductions in both pro- and anti-inflammatory cytokines than those receiving standard treatment alone. The researchers suggest that this may reflect ibuprofen’s action as a non-selective cyclooxygenase inhibitor, which may alter prostaglandin-mediated feedback loops that regulate cytokine production.
However, the researchers emphasize that these immunological patterns are exploratory and cannot be specifically attributed to ibuprofen due to the study’s small sample size, baseline differences between groups, and individual background anti-TB regimen variability.
A similar trend was observed in transcriptome analysis. Participants who received ibuprofen showed a significant reduction in blood RNA signature scores, which have previously been associated with tuberculosis treatment failure. These signatures are enriched in neutrophil-related genes, and patients who ultimately fail treatment have higher expression levels of neutrophil-related genes, suggesting that excessive inflammation before treatment may contribute to poor outcome.
Despite these encouraging biological signals, they did not lead to improved microbiological or clinical outcomes. The researchers suggested several possible explanations, including the studies’ small sample sizes, baseline imbalances between treatment groups, open-label designs, lack of a placebo control, and differences in individual anti-TB regimens.
They also propose that relatively low doses of ibuprofen may not have reduced inflammation enough to alter the course of TB disease. Taken together, these findings support further evaluation of high-dose or alternative host-directed therapies in large, adequately powered, placebo-controlled trials.
Pilot study results support large-scale ibuprofen tuberculosis trial
Overall, this pilot study highlights the feasibility of using ibuprofen 400 mg once daily as adjunctive therapy in the intensive care phase for adults with pre- or highly drug-resistant tuberculosis.
Although this finding supports further investigation of nonsteroidal anti-inflammatory drugs as host-directed therapies, the authors conclude that larger, adequately powered, placebo-controlled trials are needed to determine whether these immunological effects translate into meaningful clinical benefit.
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Reference magazines:
- Fonseca KL. (2026). Adjunctive ibuprofen in highly drug-resistant and highly drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial. Nature Communications. Doi: https://doi.org/10.1038/s41467-026-75148-9 https://www.nature.com/articles/s41467-026-75148-9
