Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication

Liang Fu; Wenfei Wang; Juan Xiong; Peize Zhang; Hui Li; Xilin Zhang; Hancheng Liang; Qianting Yang; Zhaoqin Wang; Xinchun Chen; Guofang Deng; Yi Cai; Shenjie Tang

doi:10.2147/IDR.S443897

Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication

Infect Drug Resist. 2024 Feb 17:17:595-604. doi: 10.2147/IDR.S443897. eCollection 2024.

Authors

Liang Fu^#^{1

2}, Wenfei Wang^#^{2

3}, Juan Xiong^#⁴, Peize Zhang², Hui Li², Xilin Zhang⁵, Hancheng Liang⁶, Qianting Yang², Zhaoqin Wang², Xinchun Chen³, Guofang Deng², Yi Cai³, Shenjie Tang¹

Affiliations

¹ Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People's Republic of China.
² Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China.
³ Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China.
⁴ Health Science Center, Shenzhen University, Shenzhen, Guangdong, People's Republic of China.
⁵ Tuberculosis Prevention and Control Department, the Fourth People's Hospital of Foshan, Foshan, Guangdong, People's Republic of China.
⁶ Division Two of Tuberculosis Diseases Department, the Sixth People's Hospital of Dongguan, Dongguan, Guangdong, People's Republic of China.

^# Contributed equally.

Abstract

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.

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

Grants and funding

This work was supported by the National Natural Science Foundation of China (82070016), the National Key Research and Development Program of China (2023YFC2306700, 2023YFC2306703), the Guangdong Provincial Clinical Research Center for Tuberculosis Project (2020B1111170014), the Shenzhen High-level Hospital Construction Fund (XKJS-CRGRK-008), the Shenzhen Clinical Research Center for Tuberculosis (20210617141509001), the Shenzhen Scientific and Technological Foundation (KCXFZ20211020163545004), Shenzhen Third People’s Hospital Research Fund (G2021010, G2021015, G2021023, G2022155).