ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)

Winthrop, Kevin; Mariette, Xavier; Silva, Jose T.; Benamu, Esther; Calabrese, Leonard H.; Dumusc, Alexandre; Smolen, Josef S; Aguado, José María; Fernández‐Ruiz, Mario

doi:10.1016/j.cmi.2018.02.002

Cited by 181 publications

(195 citation statements)

References 250 publications

(239 reference statements)

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“…Among the therapeutic interventions, the CANTOS trial, with 10 061 individuals, recently demonstrated that individuals receiving 150 mg of canakinumab subcutaneously every 3 months had a significant lower rate of recurrent cardiovascular events than placebo . It is important to note that these drugs are shown to moderately increase the risk of infection and there are currently no specific prevention strategies being recommended . It is speculated that further understanding of the inflammasomes will allow targeting of other components more specific to different inflammasomes that could be less immune‐suppressive than a global interleukin‐1 therapy .…”

Section: Therapeutics Targeting the Inflammasomementioning

confidence: 99%

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Marchesan

Girnary

Moss

et al. 2019

Periodontology 2000

104

106

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Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase‐1, which subsequently induces the only known form of secretion of active interleukin‐1β and interleukin‐18. Although the importance of interleukin‐1β in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid‐interleukin‐1β and grouped the participants based on current periodontal disease classifications. We review data on 4910 European‐Americans that correlate 16 polymorphisms in the interleukin‐1B region with high gingival crevicular fluid‐interleukin‐1β levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase‐1 inhibitor, VX‐765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.

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Section: Therapeutics Targeting the Inflammasomementioning

confidence: 99%

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Marchesan

Girnary

Moss

et al. 2019

Periodontology 2000

104

106

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“…However, physicians should be careful and not fully rely on the action of the vaccine. Despite the current precautions, a significant increase in Neisseria infections can be seen in eculizumab-treated individuals [67,84]. It is anticipated that the neutrophil response under eculizumab therapy is less effective since the patient is not able to form C5a, which is crucial to attract neutrophils [85].…”

Section: Eculizumabmentioning

confidence: 99%

“…Vaccine efficacy is further complicated by the fact that eculizumab and MAC-deficient patients can be infected with less invasive meningococcal strains that are not included in current vaccines [67,86]. Also, in acute cases of PNH or aHUS, postponing eculizumab therapy to await the response to vaccination may be detrimental and outweigh the risks of developing a meningococcal infection.…”

Section: Eculizumabmentioning

confidence: 99%

“…It has also been approved for the treatment of aHUS [76] and, more recently, myasthenia gravis [77]. Furthermore, the use of eculizumab in other clinical disorders is currently being explored [67]. Since patients receiving eculizumab are at risk for infections with Neisseria, the FDA has requested the implementation of a risk evaluation and mitigation strategy to minimize these infections.…”

Section: Eculizumabmentioning

confidence: 99%

“…In the past decade, many promising complement inhibitors have been developed; 2 of these (the C5 blocking antibody eculizumab and a C1-inhibitor) have been approved for clinical use, and others are currently being evaluated in clinical trials [66]. Since these inhibitors target essential elements of the host response to bacteria and other pathogens, the use of complement-inhibitory therapies has raised concerns about the increased risk of infections [29,67]. Below, we discuss the associated risks and recommended preventive measures of eculizumab therapy.…”

Section: Therapeutic Complement Inhibitors In Inflammatory Diseasesmentioning

confidence: 99%

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Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

et al. 2018

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Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the development of alternative therapies to treat infections with antibiotic-resistant bacteria. Furthermore, a variety of novel therapeutic complement inhibitors have been developed to prevent unwanted complement activation in autoimmune inflammatory diseases. A better understanding of how such inhibitors may increase the risk of bacterial infections is essential if such therapies are to be successful.

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Association Between Biologics Use and Risk of Serious Infection in Patients With Psoriasis

et al. 2021

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IMPORTANCE Biologics and targeted therapies, such as apremilast, are efficient treatments to manage moderate to severe psoriasis. More information about the risk of serious infection is needed for the newest treatment options in a real-world setting.OBJECTIVE To assess the risk of serious infection among biologics and apremilast used to treat psoriasis, with etanercept as the comparator. DESIGN, SETTING, AND PARTICIPANTSThis nationwide cohort study from France involved data from the National Health Data System covering approximately 99% of the French population. All adults with psoriasis, defined as receiving at least 2 prescriptions of a topical vitamin D derivative within a 2-year period, registered in the database between January 1, 2008, and May 31, 2019, were eligible. The study population included those who were new users of biologic agents or apremilast (ie, without any prescriptions of a biologic or apremilast during the previous year). Patients with HIV infection or a history of cancer, transplant, or serious infection were excluded. End of follow-up was January 31, 2020.MAIN OUTCOME MEASURES The primary end point was a serious infection in a time-to-event analysis using propensity score-weighted Cox proportional hazards regression models, estimating weighted hazard ratios (wHRs) and 95% CIs.RESULTS A total of 44 239 new users of biologic treatment were identified (mean [SD] age, 48.4 [13.8] years; 22 866 [51.7%] men; median follow-up, 12 months [interquartile range, 7-24 months]). A total of 29 618 (66.9%) were prescribed a tumor necrosis factor inhibitor first, 6658 (15.0%) an interleukin (IL) 12/23 inhibitor, 4093 (9.3%) an IL-17 inhibitor, 526 (1.2%) an IL-23 inhibitor, and 3344 (7.6%) apremilast. The total number of serious infections was 1656, and the overall crude incidence rate was 25.0 (95% CI, 23.8-26.2) per 1000 person-years. The most frequent serious infections were gastrointestinal infections (645 patients [38.9%]). After adjusting for time-dependent covariables, risk of serious infections was higher for new users of adalimumab (wHR, 1.22; 95% CI, 1.07-1.38) or infliximab (wHR, 1.79; 95% CI 1.49-2.16) vs etanercept, whereas ustekinumab was associated with a lower risk of having a serious infection (wHR, 0.79; 95% CI, 0.67-0.94). Risk of serious infections was not increased for new users of IL-17 and the IL-23 inhibitor guselkumab or apremilast vs etanercept. Risk of serious infections was increased with concomitant nonsteroidal anti-inflammatory drugs or systemic corticosteroids. CONCLUSIONS AND RELEVANCEIn this cohort study of individuals with moderate to severe psoriasis, risk of serious infections was increased in new users of infliximab and adalimumab vs etanercept, whereas ustekinumab users had lower risk of having a serious infection but not new users of IL-17 and IL-23 inhibitors or apremilast. Other observational studies are needed to confirm results for the most recent drugs.

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ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)

Abstract: Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.

Cited by 181 publications

References 250 publications

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

Association Between Biologics Use and Risk of Serious Infection in Patients With Psoriasis

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