Background: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB.
Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment.
Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures.
Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.

Plain Language Summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB.

Keywords: Sulfasalazine, host-directed therapy, pre-extensive drug-resistant tuberculosis, short-course, treatment