Table 1.
Drugs associated with risk of specific CNS infections
| Drug | Molecular target | Indication | CNS infections |
|---|---|---|---|
| I. Drugs approved for neurological conditions | |||
| Alemtuzumab | CD52 | Multiple sclerosis | VZV, HSV, TB, PML, CMV, Listeria, Nocardia |
| Dimethyl fumarate | Nrf2 upregulator | Multiple sclerosis | PML, VZV |
| Eculizumab | AQP4, myasthenia gravis | Neisseria meningitidis | |
| Fingolimod | Sphingosine-1-phosphate inhibitor | Multiple sclerosis | VZV, HSV, PML, Cryptococcus, Listeria |
| Natalizumab | α4 integrin inhibitor | Multiple sclerosis | PML VZV, HSV |
| Ocrelizumab | CD20 | Multiple sclerosis | VZV, HSV, PML* |
| Teriflunomide | Pyrimidine synthetase inhibitor | Multiple sclerosis | PML, TB |
| Corticosteroids (prednisone, methylprednisolone, dexamethasone) | Anti-inflammatory, T cell inhibition | Multiple indications | PML, VZV, PJP, Candida |
| II. Drugs used off label for neurological conditions | |||
| Azathioprine | Antimetabolite, purine analog | Myasthenia gravis, CIDP, AQP4, MS, polymyositis, vasculitis, neurosarcoidosis | PML, CMV, EBV-associated PCNSL |
| Cyclophosphamide | Alkylating agent | MS, MMN, neurosarcoidosis, vasculitis, lupus, inflammatory myopathies, autoimmune paraneoplastic syndromes | PML, sepsis, bacterial infections (urine, lung) |
| Ibrutinib | Bruton’s tyrosine kinase inhibitor | PCNSL | Aspergillus, PML |
| Infliximab | TNF-alpha inhibitor | Neurosarcoidosis | VZV, TB, PML, demyelinating lesions ➔ MS |
| Methotrexate | Folate analog inhibitor | Sarcoidosis, PCNSL, lupus, polymyositis | Toxoplasmosis, EBV-associated lymphoproliferative disorder |
| Mycophenolate mofetil | Inosine 5′-monophosphate dehydrogenase inhibitor | Myasthenia gravis, MS, AQP4, CIDP, neurosarcoidosis | PML, PCNSL |
| Rituximab** | CD20 | MS, AQP4, MMN, myositis, myasthenia gravis, autoimmune encephalitis, PCNSL | Toxoplasmosis, enterovirus, Babesia, WNV, CMV, VZV, Cryptococcus, PJP, Powassan virus, PML |
| III. Drugs associated with CNS infections with no primary neurological indication | |||
| Adalimumab (also certolizumab, etanercept) | TNF-alpha inhibitor | IBD, psoriasis, RA, JRA, ankylosing spondylitis | PML |
| Brentuximab | CD30 | T cell lymphoma, Hodgkin lymphoma | PML |
| Cyclosporine/tacrolimus | Calcineurin inhibitor | transplantation | |
| Fludarabine | Antimetabolite, purine analog | ALL, AML, CLL, HCT | PML, VZV, HSV, Listeria, Cryptococcus |
| Leflunomide | Pyrimidine synthase inhibitor | RA, psoriatic arthritis | PML, TB |
| Ruxolitinib | Janus kinase inhibitor | GVHD | PML, toxoplasmosis |
*PML associated with ocrelizumab to date only seen in patients previously on natalizumab or dimethyl fumarate
**Rituximab associated with reactivation of hepatitis B virus and the unusual severity of infections with Babesia and WNV
ALL, acute lymphoblastic leukemia; AML, acute myelocytic leukemia; AQP4, aquaporin-4 disease (previously, neuromyelitis optica); CIDP, chronic inflammatory demyelinating polyneuropathy; CLL, chronic lymphocytic leukemia; CMV, cytomegalovirus; EBV, Epstein–Barr virus; GVHD, graft vs. host disease; HCT, hematopoietic cell transplantation; HSV, herpes simplex virus; IBD, inflammatory bowel disease; JRA, juvenile rheumatoid arthritis; MMN, multifocal motor neuropathy; PCNSL, primary CNS, lymphoma; PJP, Pneumocystis jirovecii pneumonia; PML, progressive multifocal leukoencephalopathy; RA, rheumatoid arthritis; TB, Mycobacterium tuberculosis; TNF, tumor necrosis factor; VZV, varicella-zoster virus; WNV, West Nile virus