Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial

@article{fonseca2026adjunctive,
  title = {{Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial}},
  author = {Kaori L Fonseca and Judith Farrés and Ketevan Barbakadze and Iza Jikia and Malkhaz Tsotskhalashvili and Juan M García-Illarramendi and Lilibeth Arias and Kennedy Otwombe and Chiara Sopegno and Albert Despuig and Neil Martinson and Nadiia Buhiichyk and Tamta Korinteli and Émilie Layre and Jérôme Nigou and Zaza Avaliani and Nestani Tukvadze and Sergo Vashakidze and Cristina Vilaplana},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-75148-9},
  url = {https://hal.science/hal-05843761v1},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial
AU  - Kaori L Fonseca
AU  - Judith Farrés
AU  - Ketevan Barbakadze
AU  - Iza Jikia
AU  - Malkhaz Tsotskhalashvili
AU  - Juan M García-Illarramendi
AU  - Lilibeth Arias
AU  - Kennedy Otwombe
AU  - Chiara Sopegno
AU  - Albert Despuig
AU  - Neil Martinson
AU  - Nadiia Buhiichyk
AU  - Tamta Korinteli
AU  - Émilie Layre
AU  - Jérôme Nigou
AU  - Zaza Avaliani
AU  - Nestani Tukvadze
AU  - Sergo Vashakidze
AU  - Cristina Vilaplana
PY  - 2026
DA  - 2026/07/01
JO  - Nature Communications
DO  - 10.1038/s41467-026-75148-9
UR  - https://hal.science/hal-05843761v1
AB  - Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial A list of authors and their affiliations appears at the end of the paper Drug-resistant tuberculosis remains a major global health challenge, and excessive inflammation may contribute to tissue damage and poor outcomes. We conducted a phase IIA prospective open-label pilot trial (ClinicalTrials.gov: NCT02781909) evaluating adjunctive ibuprofen in adults with pulmonary preextensively drug-resistant (pre-XDR) or extensively drug-resistant (XDR) tuberculosis in Georgia. Twenty-eight participants received individualized background anti-tuberculosis regimens alone (n = 14) or with ibuprofen 400 mg daily for 2 months (n = 14) and were followed for 6 months. The primary efficacy outcome was the proportion of participants showing clinical and/or microbiological benefit, assessed by sputum culture conversion, radiological evolution, and WHO-defined treatment outcomes. Secondary outcomes were safety and tolerability, health-related quality of life, and inflammatory and transcriptomic responses. Adding adjunctive ibuprofen did not improve month-2 sputum culture negativity, time to stable culture conversion, radiological evolution, or final treatment outcomes. Safety and tolerability were similar between groups. Adverse events were recorded and reviewed, but not formally graded for severity. Ibuprofen treatment was associated with numerically greater reductions in several blood-based inflammatory measures and in transcriptomic signature scores associated with poor tuberculosis outcomes. These findings are exploratory and do not demonstrate clinical benefit but indicate biological activity and support evaluation of anti-inflammatory host-directed therapies in larger controlled trials.Tuberculosis (TB) disease is still claiming millions of lives annually, while imposing economic and social burdens, being one of the major problems for health systems worldwide. In 2024, nearly 400,000 TB cases emerged as multi-drug resistant (MDR) or extensively drugresistant (XDR), with concerningly low success rates in treatment 1 . Drug-resistant (DR)-TB is a major global public health challenge. Countries of Eastern Europe and Central Asia are home to 24% of the global cases of MDR-TB and 47% of the pre-extensively DR-TB cases (pre-XDR-TB) 2 . This poses a problem for European health systems, which suffer from the increased complications associated with these forms of the disease. In Georgia, the National Center for Tuberculosis and Lung Diseases (NCTLD) serves as a national referral centre for the management of complex drug-resistant TB, where patients with pre-XDR-TB and XDR-TB represent a substantial proportion of admissions. Treatment for MDR/XDR-TB is associated with poor outcomes and high mortality rates 3 . Given their greater disease severity, limited.
SN  - 2041-1723
SN  - 2041-1723
ER  -