Immunosuppressive therapy

Screening

Before starting immunosuppressive therapy, consider the following investigations:

• Tuberculin skin test
• Strongyloides serology, if from endemic country
• Hepatitis B and C serology
• Cytomegalovirus serology
• HIV serology

Management

• Latent TB infection: start treatment at least 4 weeks prior to starting the biologic

Specific Medications

Medications	Target	Type	Indications	Specific Risks
Eculizumab	C5 complement			meningococcus (very high risk; needs MCV4 + MenB + pen prophylaxis)
Rituximab	CD20			specific risk of PML and HBV; serious bacterial infections, PML, parvovirus, CMV, HSV, and disseminated VZV infections, HBV and HCV reactivation
Ocrelizumab	CD20
Natalizumab	α4-integrin	humanized IgG4		specific risk of PML; herpesvirus infections, influenza, Cryptosporidium diarrhea, bacterial pneumonia and UTI, PCP, Mycobacterium avium-intracellulare infection, Aspergillus and Burkholderia cepacia infections
Ibrutinib	Bruton's tyrosine kinase (BTK), on B cells			Invasive aspergillosis and other fungal infections
Steroids
Cyclosphosphamide	Antimetabolite
Leflunomide	Antimetabolite
Methotrexate	Antimetabolite
Azathioprine	Antimetabolite
6-mercaptopurine	Antimetabolite
Mycophenolic acid	Antimetabolite
Mycophenolate mofetil	Antimetabolite
Tacrolimus	Calcineurin inhibitor
Cyclosporine	Calcineurin inhibitor
Sirolimus	Calcineurin inhibitor
Baricitinib	JAK inhibitor
Tofacitinib	JAK inhibitor
Upadacitinib	JAK inhibitor
Adalimumab	TNF-α	human IgG1		serious pulmonary bacterial infections, TB, candidiasis, CMV infection, toxoplasmosis, and nocardiosis
Certolizumab pegol	TNF-α	humanized Fab' fragment		serious pulmonary bacterial infections, TB, viral and fungal infections
Golimumab	TNF-α
Certolizumab pegol	TNF-α
Etanercept	TNF-α	human dimeric fusion protein		serious bacterial infections, TB, NTM, listeriosis, histoplasmosis, candidiasis, aspergillosis, cryptococcosis, nocardiasis, protozoal and VZV infection
Infliximab	TNF-α	chimeric IgG1		pneumonia, sepsis, TB, NTM, listeriosis, histoplasmosis, candidiasis, aspergillosis, cryptococcosis, salmonellosis, toxoplasmosis, brucellosis, bartonellosis, leishmaniasis, coccidiomycoses, leprosy, CMV infection, HBV reactivation
Sulfasalazine	Anti-inflammatory
5-aminosalicylic acid and mesalamine	Anti-inflammatory
Anakinra	IL-1	non-glycosylated IL-1 receptor		pneumonia, cellulitis, TB, unspecified mycobacterial and fungal infections
Rilonacept	IL-1	dimeric fusion protein IL-1 inhibitor		meningitis, NTM, severe bronchitis
Canakinumab	IL-1
Tocilizumab	Anti-IL6
Sarilumab	Anti-IL6
Ustekinumab	Anti-IL12/IL23
Secukinumab	Anti-IL17	human IgG1κ monoclonal antibody	psoriasis, ankylosing spondylitis, and psoriatic arthritis
Ixekizumab	Anti-IL17
Brodalumab	Anti-IL17 receptor
Belimumab	Anti-BLyS
Guselkumab	Anti-IL23
Risankizumab	Anti-IL23
Abatacept	T-cell costimulation inhibitor	fusion protein		pneumonia, sepsis, aspergillosis, sinusitis, candidiasis, bronchitis, skin and soft tissue infection, viral infections with HSV and VZV
Fingolimod	Selective T-cell costimulation blocker
Siponimod	S1PR agonist
Ozanimod	S1PR agonist
Apremilast	Phosphodiesterase inhibitor
Vedolizumab	Anti-integrin
Efalizumab	CD11a	humanized IgG1		generally mild; pneumonia, cellulitis, abscess, sepsis, Legionella pneumonia, necrotizing fasciitis, TB, PML
Alefacept	T-cell activation	fusion protein		cellulitis, abscess, wound infections, toxic shock, pneumonia, appendicitis, cholecystitis, gastroenteritis, NTM infection, influenza virus, HCV, and herpesvirus infections
Alemtuzumab	CD52	humanized IgG1		causes prolonged lymphopenia; overwhelming bacteremia, pneumonia, meningitis, CMV, VZV, and HSV infections, PCP, PML, adenovirus infection, acanthamebiasis, toxoplasmosis, histoplasmosis, cryptococcosis, aspergillosis, Fusarium infection, Scedosporium infection, BK virus infection, HHV-6 infection, candidiasis, parvovirus infection, mucormycosis, TB, Balamuthia mandrillaris infection, NTM infection, BCG-related infection, Rhodococcus infection, HBV reactivation
90Y-ibritumomab tiuxetan	CD20	radioconjugated murine IgG1		pneumonia, sepsis, cellulitis, colitis, diarrhea, empyema, osteomyelitis, pericarditis, viral pneumonia and viral hepatitis
131I-tositumomab	CD20	radioconjugated murine IgG2		pneumonia, septicemia, bronchitis, skin infections, viral infections
Gemtuzumab ozogamicin	CD33	humanized IgG4 conjugated to calichaemicin		causes prolonged neutropenia; sepsis, pneumonia, HSV infection, usual opportunistic infections with neutropenia, unusual pathogens include Staphylococcus hominis, Agrobacterium radiobacter, Acinetobacter lwoffii, Rhodococcus, and Pantoea agglomerans
Bevacizumab	VEGF	humanized IgG1		severe neutropenia; sepsis, anaerobic liver abscess with Bacteroides fragilis, Fusarium nasal septal infection, endophthalmitis, intraocular injection including Bacillus cereus and coagulase-negative Staphylococcus
Cetuximab	ErbB1	chimeric human-murine IgG1		paronychia caused by Staphylococcus aureus, abscess, sepsis
Panitumumab	ErbB1	human IgG2		paronychia, abscess, sepsis
Trastuzumab	HER2	human IgG1		febrile neutropenia
Basiliximab	CD25	chimeric human-murine IgG1		bacterial, CMV, and HSV infections, aspergillosis, nocardiosis, candidiasis, and protozoal infections
Daclizumab	CD25	humanized IgG1		nocardiosis, legionellosis, MOTT infection, TB, viral infection with CMV, BK virus, adenovirus, HSV, RSV, or influenza virus, fungal infections with Aspergillus, Scedosporium, Cunninghamella, and Candida
Muromonab	CD3	murine IgG2		bacterial infections, including Listeria, Nocardia, and MOTT infections; infections with Aspergillus, Candida, Cryptococcus, or dermatophytes; PCP; infections with Toxoplasma gondii, CMV, EBV, HSV, hepatitis viruses, VZV, adenovirus, enterovirus, RSV, and parainfluenza virus
Abciximab	GPIIb/IIIa	Fab' fragment of chimeric human-murine IgG1		pneumonia
Omalizumab	IgE	humanized IgG1		none
Palivizumab	F protein of RSV	humanized IgG1		otitis media

Further Reading

• Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev. 2009 Apr;22(2):274-90. doi: 10.1128/CMR.00040-08