Prolonged treatment with Tadekinig alfa in adult-onset Still’s disease

Kiltz, Uta; Kiefer, David; Braun, Jürgen; Schiffrin, Eduardo J.; Girard‐Guyonvarc’h, Charlotte; Gabay, Cem

doi:10.1136/annrheumdis-2018-214496

Cited by 45 publications

(26 citation statements)

References 4 publications

(3 reference statements)

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“…Very few reagents are available to block IL‐18 in humans. In a recent clinical trial, the use of tadekinig alfa, a recombinant IL‐18 binding protein, showed positive results in adult‐onset Still's disease, supporting the assumption that IL‐18 may contribute to inflammation and immune deregulation in inflammasomopathies.…”

Section: Inflammasome‐targeted Therapies In Arthritic Diseasesmentioning

confidence: 90%

Inflammasomes contributing to inflammation in arthritis

Spel

Martinon

2020

Immunological Reviews

117

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Inflammasomes are intracellular multiprotein signaling platforms that initiate inflammatory responses in response to pathogens and cellular damage. Active inflammasomes induce the enzymatic activity of caspase‐1, resulting in the induction of inflammatory cell death, pyroptosis, and the maturation and secretion of inflammatory cytokines IL‐1β and IL‐18. Inflammasomes are activated in many inflammatory diseases, including autoinflammatory disorders and arthritis, and inflammasome‐specific therapies are under development for the treatment of inflammatory conditions. In this review, we outline the different inflammasome platforms and recent findings contributing to our knowledge about inflammasome biology in health and disease. In particular, we discuss the role of the inflammasome in the pathogenesis of arthritic diseases, including rheumatoid arthritis, gout, ankylosing spondylitis, and juvenile idiopathic arthritis, and the potential of newly developed therapies that specifically target the inflammasome or its products for the treatment of inflammatory diseases.

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Section: Inflammasome‐targeted Therapies In Arthritic Diseasesmentioning

confidence: 90%

Inflammasomes contributing to inflammation in arthritis

Spel

Martinon

2020

Immunological Reviews

117

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“…Several reports have demonstrated that levels of ‘free’ and total IL‐18 are elevated in many sHLH patients, while it has recently been reported that levels of ‘free’ IL‐18 are also significantly elevated among patients with sJIA and AOSD . These observations provided a sound rationale for an investigation of recombinant IL‐18BP as a treatment for AOSD patients in a phase II study, which demonstrated that targeting IL‐18 represents an effective therapeutic strategy . Although the studies described above have clearly established a therapeutic benefit of targeting IL‐18 activity in human disease, it is as yet unclear whether these effects can completely be ascribed to the inhibition of its IFNγ inducing activity.…”

Section: Targeting Il‐18 In Human Diseasementioning

confidence: 99%

Current perspectives on the interleukin‐1 family as targets for inflammatory disease

et al. 2019

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Since the first description of interleukin-1 (IL-1) and the genesis of the field of cytokine biology, the understanding of how IL-1 and related cytokines play central orchestrating roles in the inflammatory response has been an area of intense investigation. As a consequence of these endeavours, specific strategies have been developed to target the function of the IL-1 family in human disease realizing significant impacts for patients. While the most significant advances to date have been associated with inhibition of the prototypical family members IL-1α/β, approaches to target more recently identified family members such as IL-18, IL-33 and the IL-36 subfamily are now beginning to come to fruition. This review summarizes current knowledge surrounding the roles of the IL-1 family in human disease and describes the rationale and strategies which have been developed to target these cytokines to inhibit the pathogenesis of a wide range of diseases in which inflammation plays a centrally important role.Keywords: Canakinumab r Inflammation r Inflammatory disease r Interleukin-1 family r Therapy

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“…Tadekinig alfa has been investigated in a phase II, open-label study on patients with adult-onset Still’s disease (AOSD) showing a favorable safety profile and early signs of clinical efficacy [ 40 ]. In addition, in a recent report, prolonged administration of Tadekinig alfa was safe and shown to be associated with a marked decrease in circulating levels of free IL-18 and improvement of AOSD disease manifestations [ 41 ]. The results presented here may provide a rationale for clinical studies exploring the efficacy of Tadekinig alfa in the setting of alloSCT.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

Radujkovic

Kordelas

Bogdanov

et al. 2020

Cancers

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Interleukin-18 (IL-18) is an immunoregulatory cytokine and a context-dependent regulator of hematopoietic stem/progenitor cell (HSPC) quiescence in murine models. In a previous study, high pre-conditioning levels of IL-18 were associated with increased non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). To investigate the clinical impact of IL-18 status on hematopoietic function, the associations of pre-conditioning and day 0–3 cytokine levels with platelet and neutrophil recovery were analyzed in a training cohort of 714 allografted patients. In adjusted logistic regression analyses, both increasing pre-conditioning and day 0–3 IL-18 levels had a significantly higher adjusted odds ratio (aOR) of delayed platelet and neutrophil recovery on day +28 post-transplant (aOR per two-fold increase: 1.6–2.0). The adverse impact of high pre-conditioning IL-18 on day +28 platelet recovery was verified in an independent cohort of 673 allografted patients (aOR per two-fold increase: 1.8 and 1.7 for total and free IL-18, respectively). In both cohorts, a platelet count ≤20/nL on day +28 was associated with a significantly increased hazard of NRM (hazard ratio 2.13 and 2.94, respectively). Our findings support the hypothesis that elevated peritransplant IL-18 levels affect post-transplant HSPC function and may provide a rationale to explore modulation of IL-18 for improving alloSCT outcomes.

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Prolonged treatment with Tadekinig alfa in adult-onset Still’s disease

Cited by 45 publications

References 4 publications

Inflammasomes contributing to inflammation in arthritis

Inflammasomes contributing to inflammation in arthritis

Current perspectives on the interleukin‐1 family as targets for inflammatory disease

Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

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