# P-1202. Comparative Effectiveness of Host-Directed Therapies for Tuberculosis: A Systematic Review and Network Meta-Analysis

## TL;DR

This study compares how well different host-directed therapies work with standard tuberculosis treatment to speed up recovery.

## Contribution

The study introduces a network meta-analysis comparing multiple host-directed therapies for tuberculosis alongside standard treatment.

## Key findings

- V5 Immunitor and Immunoxel significantly improved early sputum conversion when added to standard treatment.
- Bayesian and frequentist models confirmed the effectiveness of V5 Immunitor and Immunoxel at 4 weeks.
- Metformin showed lower efficacy compared to other host-directed therapies.

## Abstract

Host-directed therapies (HDTs) are emerging as promising adjuncts to anti-tuberculosis treatment (ATT), aiming to improve early bacteriological clearance and reduce treatment failures. This network meta-analysis (NMA) evaluated the efficacy of various HDTs in achieving negative sputum conversion at 4 and 8 weeks, using standard ATT (isoniazid, rifampin, ethambutol, pyrazinamide) as the referenceGraphical AbstractGraphical abstract showing key findings.Risk of bias analysisRisk of bias

Graphical Abstract

Graphical abstract showing key findings.

Risk of bias analysis

Risk of bias

A systematic review identified randomized controlled trials (RCTs) comparing HDTs—Interleukin-2 (IL-2), Immunoxel, Metformin, Mycobacterium vaccae, Statins, V5 Immunitor, and Vitamin D—plus ATT versus ATT alone. A Bayesian random-effects NMA using a binomial likelihood with logit link estimated odds ratios (ORs) and 95% credible intervals (CrIs). A frequentist NMA was conducted for comparison. Outcomes were sputum conversion at 4 and 8 weeksCumulative rankogram of host directed therapies in TuberculosisRadiogram showing pictorial representation of various treatment armsGraph showing SUCRA scores of Host directed therapies in Tuberculosis managementGraph showing sucre scores of the various HDTs used in the studies analyzed.

Cumulative rankogram of host directed therapies in Tuberculosis

Radiogram showing pictorial representation of various treatment arms

Graph showing SUCRA scores of Host directed therapies in Tuberculosis management

Graph showing sucre scores of the various HDTs used in the studies analyzed.

Twenty-eight RCTs (4,260 patients) were included. At 4 weeks, V5 Immunitor (OR 30.7; CrI 11.0–102), Immunoxel (OR 5.68; CrI 1.82–17.4), and Mycobacterium vaccae (OR 2.05; CrI 0.996–4.94) ranked highest. IL-2, Vitamin D, and Statins showed modest, non-significant effects; Metformin had lower efficacy (OR 0.716; CrI 0.137–3.69). At 8 weeks, V5 Immunitor remained top (OR 35.4; CrI 8.89–201), followed by Vitamin D and M. vaccae. Frequentist models confirmed large effects for V5 Immunitor and Immunoxel for sputum conversion to negative at 4 weeks. Heterogeneity was moderate.

V5 Immunitor and Immunoxel significantly improved early sputum conversion when added to ATT. Findings were consistent across Bayesian and frequentist models, supporting potential inclussion of HDTs in tuberculosis therapy.

All Authors: No reported disclosures