Table 3.
Key FDA-approved immune-targeted biologics associated with the development of human fungal infections
| Molecular target | Name (and type) of biologic | Approved indications | Fungal infection susceptibility | Risk of fungal infection (mean frequency) | Non-fungal infection susceptibility | Antifungal immunological defects (when known) |
|---|---|---|---|---|---|---|
| TNF | Infliximab (mouse–human chimeric IgG1κ mAb) | RA, AS, psoriasis, IBD | Histoplasmosis, coccidioidomycosis, blastomycosis, PJP | Moderate/high | Mycobacterial infections (including disseminated TB) | Impaired IFNγ production and granuloma formation; impaired phagocyte trafficking and function |
| Etanercept (p75 TNF soluble receptor fused to the Fc portion of IgG1) | ||||||
| Adalimumab (humanized IgG1κ mAb) | Mucosal candidiasis, invasive candidiasis, aspergillosis, phaeohyphomycosis | Low (<5%) | ||||
| Golimumab (humanized IgG1κ mAb) | ||||||
| CD52 | Alemtuzumab (humanized IgG1κ mAb) | MS, CLL | Cryptococcosis, PJP, mucosal candidiasis | Moderate/high | Herpetic infections, CMV infection, toxoplasmosis, nocardiosis, pneumonias | Prolonged and profound T lymphocytopenia |
| IL-17A | Ixekizumab (humanized IgG4 mAb) | Psoriasis, AS, IBD | Mucosal candidiasis | Low/moderate (~2–12% depending on the biologic) | None | Impaired IL-17 cellular responses |
| Secukinumab (humanized IgG1κ mAb) | ||||||
| IL-17RA | Brodalumab (humanized IgG2 mAb) | |||||
| IL-12p40 | Ustekinumab (humanized IgG1κ mAb) | |||||
| IL-23p19 | Risankizumab (humanized IgG1κ mAb) | |||||
| Guselkumab (humanized IgG1λ mAb) | ||||||
| Tildrakizumab (humanized IgG1κ mAb) | ||||||
| JAK1/2/3 | Ruxolitinib, tofacitinib, baricitinib, upadacitinib, fedratinib (kinase inhibitors) | MF, PV, GvHD, RA, IBD | Histoplasmosis, coccidioidomycosis, cryptococcosis, talaromycosis, PJP, aspergillosis | Moderate/high | Herpetic infections, CMV infection, mycobacterial infections | Impaired IFNγ and IFNλ responses, impaired lymphocyte and macrophage activation, lymphopenia |
| BTK | Ibrutinib, acalabrutinib, zanubrutinib (kinase inhibitors) | CLL, MZL, MCL, WM, GvHD | Aspergillosis (with CNS involvement), mucormycosis, cryptococcosis, blastomycosis, PJP | Moderate/high | Viral and bacterial infections | Impaired myeloid phagocyte activation and function |
| PI3K (p110δ) | Idelalisib (kinase inhibitor) | CLL, lymphomas | PJP | Moderate (~5–10%) | CMV infection, pneumonias | Impaired T cell activation |
An expanded version of Table 3 is presented in Supplementary Table 3. AS, ankylosing spondylitis; BTK, Bruton’s tyrosine kinase; CLL, chronic lymphocytic leukaemia; CMV, cytomegalovirus; CNS, central nervous system; GvHD, graft-versus-host disease; IBD, inflammatory bowel disease; IFN, interferon; mAb, monoclonal antibody; MCL, mantle-cell lymphoma; MF, myelofibrosis; MS, multiple sclerosis; MZL, marginal zone lymphoma; PJP, Pneumocystis jirovecii pneumonia; PV, polycythaemia vera; RA, rheumatoid arthritis; TB, tuberculosis; TNF, tumour necrosis factor; WM, Waldenström macroglobulinaemia.