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 tuberculosis (CNS TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients is sparse. Methods We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing two groups of adults with CNS TB. Cohort-A received at least one dose of infliximab after optimal ATT and steroids, between March, 2019 to 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 from the start of ATT and steroids to infliximab treatment was 6 (IQR 3.7-13) months, and 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. In the combined study population, only exposure to infliximab was positively associated (aRR 6.2, p=0.001, 95% CI 2.18-17.83) with disability-free survival at 6-months. There were no clear infliximab related side effects noted. Conclusion 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.

Recent advances in understanding the human host immune response in tuberculous meningitis

“…The median duration from start of ATT and corticosteroid treatment was six months. The cohort only included one PLWH ( 126 ). A randomised trial is needed to investigate whether these improved outcomes with infliximab are seen more generally when administered alongside ATT from diagnosis.…”

Interventions to prevent post-tuberculosis sequelae: a systematic review and meta-analysis

“…There were 5 studies representing 806 participants that evaluated the impacts of interventions in preventing post-TB neurological sequelae such as neuromotor disability, hemiparesis, quadriparesis, and neurological deficits ( Table 5 ). 33 , 34 , 35 , 36 , 37 The overall incidence rate of neurological sequelae was 282 per 1000 TB survivors (239 per 1000 TB survivors in the intervention group and 330 per 1000 TB survivors in the control group). We identified two main components of interventions delivered in the study: adjunctive therapy and rehabilitation programs.…”

“…Few studies have investigated the effects of rehabilitation programs and adjunctive therapy on preventing post-TB neurological impairment and findings are inconsistent. 33 , 34 , 35 , 36 , 37 The pooled meta-analysis of adjunctive therapy revealed no statistically significant difference in neurological impairment incidence between the intervention and control groups, whereas a separate study on rehabilitation programs showed a significant reduction in neurological impairment within the intervention group compared to controls. While these findings suggest the potential benefit of rehabilitation programs in preventing neurological sequelae following TB treatment, further studies are needed to establish conclusive evidence.…”

Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption

“…Forty of 90 patients had a paradoxical reaction, 19 of whom were treated with infliximab. Overall, infliximab treatment was the only parameter associated with disability-free survival at 6 months [ 15 ].…”

“…It ranges from symptomatic treatment to predominantly anti-inflammatory approaches, often including corticosteroid therapy [ 13 ]. Paradoxically, a handful of studies report the use of anti-TNFα agents in this context [ 14 , 15 ].…”