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Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months...

The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory...

The clearance of both tumors and microbes depends on highly coordinated immune responses that are sufficiently potent to kill malignant or microbial cells while avoiding immunopathology from an overly exuberant inflammatory response. A molecular understanding of the immune pathways that regulate these responses paved the way for the development of checkpoint inhibitors (CPIs) as a therapeutic strategy to boost endogenous antitumor immunity. CPIs have demonstrated survival benefits across a...

The recognition of the role of complement and Janus kinase (JAK)–dependent cytokines in the pathogenesis of inflammatory and immune-mediated disorders has revolutionized the treatment of a myriad of rheumatological and inflammatory diseases. C5 inhibitors and Janus kinase inhibitors have emerged as attractive therapeutic options. Because of the blockage of immune pathways, these targeted therapies carry an increased risk of infection. This article reviews the mechanism of action and the...

Biologic therapies have revolutionized the treatment of immune-mediated inflammatory diseases but are associated with an increased risk of serious and opportunistic infections, including tuberculosis and nontuberculous mycobacterial disease. Despite this increased risk, the overall risk-benefit ratio remains favorable with appropriate screening and risk assessment. Further population-based studies are needed to establish the risk of tuberculosis and nontuberculous mycobacterial disease with...

Biologic therapies including monoclonal antibodies, tyrosine kinase inhibitors, and other agents represent a notable expansion in the pharmacotherapy armamentarium in treatment of a variety of diseases. Many of these therapies possess direct or indirect immunosuppressive and immunomodulatory effects, which have been associated with bacterial, viral, and fungal opportunistic infections. Careful screening of baseline risk factors before initiation, targeted preventive measures, and vigilant...

Lymphocyte depletion and blockade of T-cell activation and trafficking serve as therapeutic strategies for an enlarging number of immune-mediated diseases and malignancies. This review summarizes the infection risks associated to monoclonal antibodies that bind to the α chain of the interleukin-2 receptor, the cell surface glycoprotein CD52, and members of α4- and β2-integrin families acting as cell-adhesion molecules. An outline of the mechanisms of action, approved indications and...

Herpesviruses such as herpes simplex virus (HSV) type 1 and 2, varicella-zoster virus (VZV), and cytomegalovirus (CMV) maintain lifelong latency in the host after primary infection and can reactivate periodically either as asymptomatic viral shedding or as clinical disease. Immunosuppression, including biologic therapy, may increase frequency and severity of herpesvirus reactivation and infection. Licensed biologics are reviewed regarding their risks of potentiating HSV, VZV, and CMV...

The emergence of biologics has revolutionized the way physicians treat many autoimmune inflammatory conditions. Although biologics have become a vital component of the treatment approach to many inflammatory diseases, these agents may potentially disrupt the natural immune response against pathogens, thereby increasing the risk for infections. Some infections may be preventable or have a lessened risk through appropriate vaccinations; thus, vaccination history should be taken carefully in...

Tyrosine kinase inhibitors represent the standard of care for several diseases and drug targets in hematologic malignancies. Infectious complications vary by disease status and prior therapy, but overall incidence of infections generally is low. In chronic diseases, such as chronic myeloid leukemia and chronic lymphocytic leukemia, patients can remain on tyrosine kinase inhibitor therapy for many years, with few infectious complications from therapy. Bruton tyrosine kinase inhibitors overall...

Targeting interleukins that drive innate inflammation has expanded treatments of autoinflammatory and autoimmune disorders. Interleukin (IL)-1 inhibition has proven useful for monogenic autoinflammatory syndromes, and IL-6 inhibition for autoimmune arthritides. Biological therapies impeding these pathways impair detection and containment of pathogens, particularly invasive bacteria, reflecting the importance of IL-1 and IL-6 in communicating danger throughout the immune system. Biologics...

The risk of JC polyomavirus encephalopathy varies among biologic classes and among agents within the same class. Of currently used biologics, the highest risk is seen with natalizumab followed by rituximab. Multiple other agents have also been implicated. Drug-specific causality is difficult to establish because many patients receive multiple immunomodulatory medications concomitantly or sequentially, and have other immunocompromising factors related to their underlying disease. As use of...

Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic...

This article analyzes the risk of infection associated with small molecule kinase inhibitors used to treat solid organ malignancies and establishes specific recommendations. Most of these drugs are orally administered and have the ability to inhibit distinct kinases, which play a major role in cancer initiation and progression. Although the true extent of adverse events is not yet known, risk of infection does not seem to be a major problem with these drugs. Because of the limited clinical...

Co-stimulatory T-cell inhibitors are used in the treatment of rheumatoid arthritis and to prevent rejection of renal transplants. Inhibitors of the intereukin (IL-17) cytokine are indicated for psoriasis, psoriatic arthritis and ankylosing spondylitis and anti- IL-23 drugs for psoriasis. Serious infections occur in 4.2% to 25.0% of co-stimulatory inhibitors and 1.0% to 2.0% with IL-17 or IL-23 inhibitors. Underlying disease, steroid dose greater than 7.5 to 10.0 mg, and comorbidities...

There are only scattered case reports documenting belatacept use in HIV + kidney transplant recipients. We performed a retrospective review to describe short-term outcomes following conversion to belatacept in a cohort of HIV + patients. Patients were included if they were converted to belatacept between May 2015 and May 2019, had an HIV- donor, and received ≥4 doses of belatacept. All patients were treated with non-depleting induction and triple maintenance immunosuppression. Allograft and...

Background: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies.

Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-a (TNF-a) and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: Preclinical and clinical...

Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: The risk and...

Background: The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians.