Standardized Infliximab Regimen to Treat Severe Central Nervous System Tuberculosis: A Case Series of 18 Patients

Abstract

Background: Morbidity associated with central nervous system tuberculosis (CNS TB) remains high due to persistent inflammation despite standard-of-care (SOC) treatment, including antituberculosis therapy and corticosteroids. Tumor necrosis factor alpha (TNF-α) is a key cytokine driving this inflammatory response, and a limited number of case reports suggest that TNF-α inhibitors may improve outcomes. We report the 1-year outcome of a cohort of consecutive patients treated with infliximab for severe CNS TB.

Methods: Following the guidance provided by the French Tuberculosis Consilium, a standardized regimen of intravenous infliximab at 5 mg/kg per dose was used to treat CNS TB unresponsive to SOC. We retrospectively included consecutive patients who received at least 1 infliximab injection for CNS TB from 2017 to September 2021.

Results: Eighteen patients with CNS TB, 94% with tuberculous meningitis, were included. Most had severe disease: 82% were classified as British Medical Research Council grade II or III, and 44% required intensive care unit admission. All demonstrated clinical and radiological worsening despite SOC; in 89% due to paradoxical reaction. At infliximab initiation, symptoms remained disabling, with a median modified Rankin scale (mRS) score of 3.5 (interquartile range, 3-4). One month after the first infusion, 38% showed improved mRS scores, increasing to 78% at 1 year. One-year survival was 94%; 1 death occurred 12 months after a single infliximab dose and was unrelated to TB treatment.

Conclusions: Infliximab may represent a promising adjunctive treatment for CNS TB unresponsive to SOC, including paradoxical reaction. Prospective studies are needed to confirm these findings.

Keywords: TNF-α inhibitor; central nervous system tuberculosis; infliximab; paradoxical reaction; tuberculous meningitis.

Figure 1.

Evolution of mRS over time: (A) in all patients (n = 18), TB, mRS scores available for 18 patients; M0, mRS scores available for 18 patients; M1, M3, M6, and M12, mRS scores available for 16, 14, 14, and 18 patients, respectively; (B) in patients with mRS ≥ 3 at M0 (n = 14); (C) in patients with mRS ≤ 2 at M0 (n = 4). *One patient died at 12 m (M12) after receiving a single injection of infliximab. Abbreviations: TB, tuberculosis diagnosis; M0, infliximab initiation; M1, M3, M6, and M12, 1, 3, 6, and 12 m postinfliximab initiation.

Figure 2.

Radiological and Clinical Improvement Following Infliximab Initiation in 2 Representative Patients. Top row: MRI images (T1 with contrast) from a patient presenting with febrile confusion and new-onset voluminous tuberculomas at 5 m of standard treatment. Despite antituberculosis therapy and high-dose steroids, tuberculoma size, and perilesional edema increased (top left). Initiation of infliximab led to significant radiological improvement at 3 (top middle) and 6 (top right) months. Bottom row: MRI images from a second patient with clinical worsening despite antituberculosis therapy and CSs, requiring ventricular shunting due to a new abscess at the base of the skull (bottom left). Following infliximab initiation, MRI at 3 (bottom middle) and 6 (bottom right) months demonstrated significant radiological and clinical improvement.