Infliximab may be an efficacious and safe adjuvant for patients significantly disabled with severe central nervous system tuberculosis (CNS TB) who are not responsive to optimal antitubercular therapy (ATT) and steroids, according to study findings published in Clinical Infectious Diseases.
Study authors sought to assess the effectiveness of infliximab (a tumor necrosis factor alpha [TNF-α] inhibitor with good CNS penetration) adjunctive therapy when added to ATT and steroids in patients with CNS TB. Disability-free survival (defined as modified Rankin Scale [mRS] ≤2) at 6-months was the primary endpoint.
Investigators conducted a matched retrospective cohort study of patients (mean age, 31 years) with severe CNS TB at a teaching hospital in South India from March 2019 to July 2022. A cohort of 30 patients treated with optimal ATT and steroids and at least 1 dose (10 mg/kg) of infliximab (cohort A) was matched 1:2 with a cohort of 60 adult patients treated with optimal ATT and steroids only (cohort B).
The researchers identified subgroups most likely to benefit from infliximab in addition to standard of care; these were patients with CNS TB with new onset or persistent unimproved deficits despite optimal ATT and steroids with recent onset arachnoiditis with paraparesis, optochiasmatic TB with visual deficits, recurrent clinical worsening on steroid tapering, and refractory symptomatic tuberculomas. Most of the patients chosen for the infliximab cohort (A) presented with paradoxical worsening, and almost all of the patients in this cohort had focal neurological deficits.
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In a carefully selected group of patients with CNS TB, who continue to worsen despite optimal ATT and steroids, adjunctive infliximab therapy may be a safe and effective agent to improve disability free survival.
Cohort B was matched for mRS scores and Medical Research Council (MRC) grades for TB meningitis only. Indications for infliximab were optochiasmatic arachnoiditis (3/30), spinal cord involvement with paraparesis (8/30), and symptomatic tuberculomas (20/30) worsening despite optimal treatment with ATT and steroids.
Focal neurological deficits were found at baseline in cohort A in 26/30 patients (severely disabled); among these patients, 19/30 showed paradoxical worsening. Before infliximab treatment, median duration of neurological deficits was 4 months (interquartile range [IQR], 2.0-6.2 months). From start of ATT and steroids to consideration of infliximab therapy, median duration was 6 months (IQR, 3.7-13.0 months). Among patients receiving infliximab, 19 received 3 doses, 7 received 2 doses, 4 received 1 dose.
Among patients in cohort B, median duration of neurological deficits was 2 months (IQR, 1-5 months). Median duration of ATT and steroid treatment was 12 months (IQR, 7.3-18 months). Focal neurological deficits were found at baseline in 50/60 patients.
Investigators noted marked neurological improvement after the first dose in all 25 patients who improved on infliximab. In cohort A, there were no immediate infusion-related adverse events; 19/26 patients had radiological improvement, 5/26 had stable disease, 2/26 had worsening (4 patients did not undergo follow-up imaging).
At 6 months, compared with cohort B, cohort A had a higher likelihood of success (risk ratio, 2.3; 95% CI, 1.28-4.36).
Investigators found at 6 months, all-cause mortality was lower in cohort A vs cohort B (6.7% vs 21.7%) as was severe disability (16.7% vs 35.0%). Only exposure to infliximab was positively associated with survival, disability-free at 6 months (adjusted risk ratio, 6.2; 95% CI, 2.18-17.83; P =.001) in the combined study population.
Study limitations include the retrospective design and underpowered sample size.
“In a carefully selected group of patients with CNS TB, who continue to worsen despite optimal ATT and steroids, adjunctive infliximab therapy may be a safe and effective agent to improve disability free survival,” investigators concluded. They added that “Infliximab potentially improved every third patient compared to conventional therapy,” although clinicians must be careful to identify patients most likely to benefit from infliximab, given its expense and the lack of effect in certain patients.
