Page 550 - Clinical Immunology_ Principles and Practice ( PDFDrive )

528 Part four Immunological Deficiencies

Mycophenolate Mofetil Tumor Necrosis Factor-α Inhibitors
Mycophenolate mofetil (MMF) is a prodrug of mycophenolic TNF-α is a cytokine that plays a central role in macrophage and
acid, which inhibits inosine monophosphate dehydrogenase, a phagosome activation, differentiation of monocytes into mac-
key enzyme in purine synthesis. It is a cytotoxic drug with rophages, recruitment of neutrophils and macrophages, and
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antiproliferative effect on T and B lymphocytes. In addition granuloma formation and maintenance. Blockade results in an
to its potential myelosuppressive effect, it has been associated increased risk of infection, particularly in the first few months
in SOT to a higher risk of CMV infection. 32 after treatment. 37,38 Infections characterized by granulomas have
been described most frequently, in particular TB and NTM
Antithymocyte Globulin infections, but also disseminated histoplasmosis and coccidioi-
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Antithymocyte globulin (ATG) is a polyclonal Ig prepared by domycosis. Other notable infections are listeriosis, legionellosis,
immunizing horses or rabbits with human thymocytes and salmonellosis, recurrent or relapsing leishmaniasis, overwhelming
harvesting the IgG. These antibodies produce a profound lym- Plasmodium falciparum infection, and invasive mold infections
phopenia that can last well beyond 1 year. Used for induction or (i.e., aspergillosis and mucormycosis). Risk of certain viral
rejection therapy in transplantations, their use has been associated infections also appears to be increased, particularly VZV infection.
consistently with a greater risk of CMV and posttransplantation Several cases of severe hepatitis B virus (HBV) reactivation in
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lymphoproliferative disease (PTLD). CMV prophylaxis or patients with positive surface antigen at the start of treatment
preemptive therapy is recommended in transplant recipients that have been reported, many of whom developed hepatic failure.
receive ATG. Because these are foreign proteins, serum sickness Patients receiving anti–TNF-α therapy should be screened for
can also develop between 1 and 2 weeks after treatment. TB (latent or active), HBV, and HCV before starting treatment,
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and treated accordingly. Patients with latent TB should receive
Monoclonal Antibodies and Small Molecules isoniazid for 6–9 months. Ideally, patients would have received
Monoclonal antibodies (mAbs) and small molecules target specific at least 3 weeks of isoniazid before therapy with biologicals;
cellular steps, making it possible to manipulate disease pathways however, in truly urgent cases, this can be done simultaneously.
for previously untreatable illnesses. Many of these biological In patients that are hepatitis B surface antigen (HbsAg) positive,
agents interfere with specific aspects of the immune system. baseline HBV DNA levels should be obtained and antiviral
Highlighted below are those that have a key infection susceptibility prophylaxis or treatment offered. All HBV-seronegative patients
pattern. Others with more subtle increases in infections are also should be vaccinated against hepatitis B and seroconversion
included in Table 37.2. documented.

TABLE 37.2 Selected Monoclonal antibodies and Small Molecules and their risk of Infection
Drug Name target Serious Infections
Adalimumab TNF-α* TB, NTM infection, endemic mycoses, listeriosis, candidiasis, invasive mold infections,
Certolizumab pegol nocardiosis, bacterial infections, reactivation of VZV and HBV infections, severe malaria, and
Etanercept leishmaniasis
Golimumab
Infliximab
Rituximab CD20 HBV infection reactivation, PML, PCP, enteroviral meningoencephalitis, CMV disease, VZV
infection, babesiosis, parvovirus infection, nocardiosis
Anakinra IL-1 Bacterial infections (cellulitis and pneumonia)
Rilonacept
Alemtuzumab CD52 Herpes viruses reactivation (EBV, VZV, CMV, HHV-6), severe respiratory viral infections (with
adenovirus, RSV, parainfluenza virus, influenza virus), PCP, invasive mold infections,
histoplasmosis, cryptococcosis, PTLD, bacterial meningitis, toxoplasmosis, PML, parvovirus
infection, nocardiosis, TB, NTM infection, acanthamebiasis, and Balamuthia mandrillaris infection
Muromonab CD3 Bacterial infections; listeriosis; nocardiosis; aspergillosis; candidiasis; cryptococcosis;
toxoplasmosis; infections with CMV, HSV, VZV, adenovirus, RSV, and enteroviruses; and PCP
Basiliximab CD25 Bacterial infections; infections with CMV and HSV; EBV-associated PTLD; infections with RSV,
Daclizumab adenovirus, influenza, and BK virus; invasive mold infections; candidiasis; nocardiosis; TB; NTM
infection; toxoplasmosis
Natalizumab α-4 Integrin PML, respiratory viral and bacterial infections, UTI, viral meningitis and encephalitis, CMV
infection, IA, PCP, VZV infection, NTM infection, cryptosporidiosis
Abatacept T-cell costimulation blockade Bacterial infections, EBV-associated PTLD
Belatacept
Alefacept Inhibits T-cell activation 1 case of Mycobacterium avium intracellulare (MAI) bursitis, 1 case of nocardiosis when
coadministered with infliximab
Brodalumab IL 17 receptor A Mucocutaneous candidiasis
Bortezomib Proteasome inhibitor Herpes zoster
Gemtuzumab CD33 Bacteremia, bacterial pneumonia, and HSV reactivation.
*TNF-α, tumor necrosis factor-α; IL-1, interleukin-1; TB, tuberculosis; NTM, nontuberculous mycobacteria; VZV, varicella-zoster virus; HBV, hepatitis B virus; PML, progressive
multifocal leukoencephalopathy; PCP, Pneumocystis jiroveci pneumonia; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HHV-6, human herpes virus 6; RSV, respiratory syncytial
virus; PTLD, posttransplantation lymphoproliferative disease; HSV, herpes simplex virus; UTI, urinary tract infection; IA, invasive aspergillosis.