Randomized Trial of Thalidomide and Infliximab in Paradoxical Worsening in Patients of Tuberculous Meningitis (TBM): A Clinical, Radiological and Biomarker based Study

Patients with Diagnosed Tuberculous Meningitis can paradoxically worsen after starting Antitubercular Treatment (ATT) and steroids. Paradoxical worsening manifests as vision loss, myelopathy, cranial nerve deficits, and hydrocephalus, due to arachnoiditis. We are proposing TBM as both a paucibacillary infectious and Immunological disorder, which needs stronger immunomodulation in patients with paradoxical responses.

With this background, all patients who fulfill Marais’s criteria for TBM, already being followed up every month in the TBM Clinic of PGIMER, Chandigarh will be assessed for paradoxical worsening. After confirming radiologically, these patients will be subjected to CSF analysis to rule out MDR TB or alternate infections and assess cytokine levels in CSF and serum. All the cases will be evaluated independently by 2 Neurologists with experience in Neuro infections and 1 infectious disease expert. Diagnosis of paradoxical worsening will be reached by consensus. Thereafter, these patients will be randomized to Thalidomide or Infliximab arm vs standard care (Steroids). All patients will be followed up monthly for any complications till the completion of therapy. However, repeat radiological, and biomarkers (TNF alpha, VEGF, IL-6, and IL-10) responses will be measured at 3 months. The outcome of the three groups will be analyzed at the end of the study. If required, an interim analysis will be done.