Table 4. Host directed therapies for TBM.

	Activity in TBM	Clinical use	CNS exposure	Safety
Corticosteroids	Large RCTs: Adults: 25% lower mortality 3, smaller effect for MRC grade 2/3 and with longer follow up 71; no effect on disability; uncertain effect in HIV 26. Scarce data among African adults and Asian paediatric TBM	Guideline- recommended for all patients with TBM, including IRIS and paradoxical reactions	Good	Excellent in TBM RCT 76
Aspirin	Small RCT: Possibly fewer new-onset strokes at high doses among adults with TBM 65	Not in routine clinical use, evaluated in adults and children with new TBM diagnosis	Good	No signal of severe bleeding events 77
Thalidomide	Individual case reports of resolution from mass lesions and blindness related to optochiasmatic arachnoiditis (children)	Steroid-refractory TBM or paradoxical reactions	Good	Dose related toxicity, paediatric RCT stopped prematurely for safety 60
TNF blockers (infliximab)	Case series 57,59,78 and matched retrospective cohort 58 showing clinical benefit in TBM	Steroid-refractory TBM or paradoxical reactions	Good	No serious safety signals, Risk of secondary infection
Anti-IL1 (anakinra)	Case reports in TBM 70,79	Steroid-refractory TBM or paradoxical reactions	Good	Good safety profile, associated with mild neutropenia
mTOR inhibitors	RCT: Less post-TB lung disease	No experience in TBM	Unknown	Well tolerated in an RCT for PTB
JAKi	Cases reports for HLH / HLH-TB 80	No experience in TBM		Good safety profile, associated with VZV/HSV