Immunosuppressive therapy: Difference between revisions

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= Immunosuppressive therapy =

== Screening ==
== Screening ==


Before starting immunosuppressive therapy, consider the following investigations:
Before starting immunosuppressive therapy, consider the following investigations:


* Tuberculin skin test
* [[Tuberculin skin test]]
* Strongyloides serology, if from endemic country
* [[Strongyloides]] serology, if from endemic country
* Hep B and C serology
* [[Hepatitis B]] and [[Hepatitis C virus|C]] serology
* Cytomegalovirus serology
* [[Cytomegalovirus]] serology
* HIV serology
* [[HIV]] serology


== Management ==
== Management ==


* Latent TB infection: start treatment at least 4 weeks prior to starting the biologic
* [[Latent tuberculosis infection|Latent TB infection]]: start treatment at least 4 weeks prior to starting the biologic


== Specific Medications ==
== Specific Medications ==


{| class="wikitable sortable"
{|
! Medications
! Medications
! Target
! Target
!Type
!Indications
! Specific Risks
! Specific Risks
|-
|-
| Eculizumab
| [[Eculizumab]]
| C5 complement
| C5 complement
|
| Meningococcus (very high risk), needs MCV4 + MenB + pen prophylaxis
|
| [[meningococcus]] (very high risk; needs MCV4 + MenB + pen prophylaxis)
|-
|-
| Rituximab
| [[Rituximab]]
| CD20, on B cells
| CD20
|
| Long-term B cell depletion
|
|specific risk of [[PML]] and [[HBV]]; serious bacterial infections, [[PML]], [[parvovirus]], [[CMV]], [[HSV]], and disseminated [[VZV]] infections, [[HBV]] and [[HCV]] reactivation
|-
|-
|[[Ocrelizumab]]
| Natalizumab
|CD20
| α4-integrin, on all leukocytes except neutrophils
|
| JC virus
|
|
|-
| [[Natalizumab]]
| α4-integrin
|humanized IgG4
|
| specific risk of [[PML]]; [[Herpesviridae|herpesvirus]] infections, [[influenza]], [[Cryptosporidium]] diarrhea, bacterial [[pneumonia]] and [[UTI]], [[Pneumocystis jirovecii|PCP]], [[Mycobacterium avium-intracellulare]] infection, [[Aspergillus]] and [[Burkholderia cepacia]] infections
|-
|-
| Ibrutinib
| [[Ibrutinib]]
| Bruton's tyrosine kinase (BTK), on B cells
| Bruton's tyrosine kinase (BTK), on B cells
|
|
|
| Invasive [[aspergillosis]] and other [[Invasive fungal infection|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]], [[Protozoa|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 [[Mycobacteria|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 syndrome|toxic shock]], [[pneumonia]], [[appendicitis]], [[cholecystitis]], [[gastroenteritis]], [[NTM]] infection, [[influenza virus]], [[HCV]], and [[Herpesviridae|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|<sup>90</sup>Y-ibritumomab tiuxetan]]
|CD20
|radioconjugated murine IgG1
|
|[[pneumonia]], [[sepsis]], [[cellulitis]], [[colitis]], [[diarrhea]], [[empyema]], [[osteomyelitis]], [[pericarditis]], viral [[pneumonia]] and [[viral hepatitis]]
|-
|[[131I-tositumomab|<sup>131</sup>I-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 [[Protozoa|protozoal infections]]
|-
|[[Daclizumab]]
|CD25
|humanized IgG1
|
|[[nocardiosis]], [[legionellosis]], [[Non-tuberculous mycobacteria|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 [[Non-tuberculous mycobacteria|MOTT]] infections; infections with [[Aspergillus]], [[Candida]], [[Cryptococcus]], or [[dermatophytes]]; PCP; infections with [[Toxoplasma gondii]], [[CMV]], [[EBV]], [[HSV]], [[Viral hepatitis|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: [https://doi.org/10.1128/CMR.00040-08 10.1128/CMR.00040-08]

[[Category:Immunocompromised hosts]]

Latest revision as of 18:19, 6 June 2023

Screening

Before starting immunosuppressive therapy, consider the following investigations:

Management

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
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