Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

Abstract

BACKGROUND:

Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse.

METHODS:

We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome.

RESULTS:

Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted.

CONCLUSIONS:

Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

• Authors: Abi Manesh, Priyanka Gautam, Selwyn Selva Kumar D, Pavithra Mannam, Anitha Jasper, Karthik Gunasekaran, Naveen Cherian Thomas, Rohit Ninan Benjamin, Leeberk Raja Inbaraj, Emily Devasagayam, Mithun Mohan George, Rajiv Karthik, Ooriapadickal Cherian Abraham, Harshad A Vanjare, Ajith Sivadasan, Prabhakar Thirumal Appaswamy, Edmond Jonathan, Joy S Michael, Prasanna Samuel, George M Varghese
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 77 Issue 10 Pg. 1460-1467 (11 17 2023) ISSN: 1537-6591 [Electronic] United States
• PMID: 37405816 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antitubercular Agents
• Infliximab
• Steroids

Topics

• Adult
• Humans
• Antitubercular Agents (adverse effects, pharmacology)
• Disabled Persons
• Infliximab (adverse effects, pharmacology)
• Retrospective Studies
• Steroids
• Treatment Outcome
• Tuberculosis, Central Nervous System (drug therapy)