Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies

Cabral, Vanderlea Poeys; Andrade, Carlos Augusto Ferreira de; Passos, Sônia Regina Lambert; Martins, Mônica; Hökerberg, Yara Hahr Marques

doi:10.1016/j.rbre.2016.10.001

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…The prospective follow-up of CAPS patients treated with anakinra shows a median yearly rate of 7.7 adverse events per patient, among which most of the severe adverse events are infections ( 193 ). Likewise, a systematic review finds that 129 (5.1%) severe infections were reported in 2,896 patients treated with anakinra ( 194 ). Conversely to its effect in such chronic diseases, the role of anakinra in severe acute infections may be less clear due to concomitant potential beneficial effects in sepsis.…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Inflammasomes in Tissue Damages and Immune Disorders After Trauma

2018

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Trauma remains a leading cause of death worldwide. Hemorrhagic shock and direct injury to vital organs are responsible for early mortality whereas most delayed deaths are secondary to complex pathophysiological processes. These processes result from imbalanced systemic reactions to the multiple aggressions associated with trauma. Trauma results in the uncontrolled local and systemic release of endogenous mediators acting as danger signals [damage-associated molecular patterns (DAMPs)]. Their recognition by the innate immune system triggers a pro-inflammatory immune response paradoxically associated with concomitant immunosuppression. These responses, ranging in intensity from inappropriate to overwhelming, promote the propagation of injuries to remote organs, leading to multiple organ failure and death. Some of the numerous DAMPs released after trauma trigger the assembly of intracellular multiprotein complexes named inflammasomes. Once activated by a ligand, inflammasomes lead to the activation of a caspase. Activated caspases allow the release of mature forms of interleukin-1β and interleukin-18 and trigger a specific pro-inflammatory cell death termed pyroptosis. Accumulating data suggest that inflammasomes, mainly NLRP3, NLRP1, and AIM2, are involved in the generation of tissue damage and immune dysfunction after trauma. Following trauma-induced DAMP(s) recognition, inflammasomes participate in multiple ways in the development of exaggerated systemic and organ-specific inflammatory response, contributing to organ damage. Inflammasomes are involved in the innate responses to traumatic brain injury and contribute to the development of acute respiratory distress syndrome. Inflammasomes may also play a role in post-trauma immunosuppression mediated by dysregulated monocyte functions. Characterizing the involvement of inflammasomes in the pathogenesis of post-trauma syndrome is a key issue as they may be potential therapeutic targets. This review summarizes the current knowledge on the roles of inflammasomes in trauma.

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Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Inflammasomes in Tissue Damages and Immune Disorders After Trauma

2018

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“…The most common adverse effects of these drugs are opportunistic infections and cardiovascular disorders [71]. However, the risk of malignancies is not much prevalent in biologic drugs [72,73]. The opportunistic infections are more common in case of JAK inhibitors especially the herpes zoster infection [71].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Challenges for biosimilars: focus on rheumatoid arthritis

Akram

Pery

Butler

et al. 2020

Critical Reviews in Biotechnology

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Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFa mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFa inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.

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“…While the first cause hormonal changes (leading to suppression of adrenal function and bone loss) and Cushing syndrome [28], the later induces heart failure [29]. Moreover, corticosteroids, immunobiological agents, and opioids are linked with immunosuppression and consequently pathogen spread [30][31][32]. Thus, the search for natural compounds with lower adverse effects on patients has been growing, and over the past years higher attention has been given to the flavonoids.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

et al. 2020

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Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

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Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies

Cited by 27 publications

References 26 publications

Inflammasomes in Tissue Damages and Immune Disorders After Trauma

Inflammasomes in Tissue Damages and Immune Disorders After Trauma

Challenges for biosimilars: focus on rheumatoid arthritis

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

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