Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome

Lachmann, HJ; Koné‐Paut, Isabelle; Kuemmerle‐Deschner, Jasmin; Leslie, Kieron; Hachulla, É.; Quartier, Pierre; Gitton, Xavier; Widmer, A.; Patel, Neha; Hawkins, Philip N.

doi:10.1056/nejmoa0810787

Cited by 779 publications

(638 citation statements)

References 14 publications

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“…4,17,18 Importantly, the presence of other family members with similar symptoms should always be ruled out in patients with ACU, because specific treatments (eg, antieinterleukin-1) have demonstrated effectiveness in the management of familial cold-induced urticaria syndromes. [19][20][21] Moreover, regardless of the prescribed treatment, self-limited evolution can be seen in some patients with ACU. In the present study, almost 26% of the patients experienced complete symptom resolution (and therefore no need for treatment) during the surveillance period, with a mean disease duration until resolution of 5.1 years.…”

Section: Discussionmentioning

confidence: 99%

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

Deza

Brasileiro

Bertolín‐Colilla

et al. 2016

Journal of the American Academy of Dermatology

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Section: Discussionmentioning

confidence: 99%

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

Deza

Brasileiro

Bertolín‐Colilla

et al. 2016

Journal of the American Academy of Dermatology

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“…Children with severe CAPS show manifestations of elevated intracranial pressure and are believed to be mentally slow or even retarded. However, both mental and hearing impairment are reversed on treatment with anakinra (23,102,104-107) but also with specific neutralization of IL-1β with canakinumab (103,(108)(109)(110)(111). Meniere disease can also be characterized by progressive sensorineural hearing loss and is also associated with dysregulation of IL-1β (98,99,112).…”

Section: Autoimmune Hearing Lossmentioning

confidence: 99%

An Expanding Role for Interleukin-1 Blockade from Gout to Cancer

Dinarello

2014

Mol Med

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There is an expanding role for interleukin (IL)-1 in diseases from gout to cancer. More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed "toll IL-1 receptor (TIR) domain," signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory disease. However, a role for IL-1α in disease is being validated because of the availability of a neutralizing monoclonal antibody to human IL-1α. There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist, which binds to the IL-1 receptor and prevents the binding of IL-1β as well as IL-1α. Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1β but also IL-1α. Canakinumab is a human monoclonal antibody that neutralizes only IL-1β. Thus, a causal or significant contributing role can be established for IL-1β and IL-1α in human disease.

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“…20 Not surprisingly therefore, IL-1R antagonist and anti-IL-1 monoclonal antibodies (mAbs) have transformed the previously poor historical prognostic outcome of these diseases. 23,24 Although NALP3 is functionally similar to other PRRs, including the NOD-like receptor, NOD2, in humans, a rare point mutation in NOD2 results in granulomatous inflammation in the eye, joints, and skin called Blau's syndrome. 25 Additionally, polymorphic variations in NOD2 increase susceptibility to Crohn's disease, which is not infrequently associated with uveitis.…”

Section: Understanding Immunopathologymentioning

confidence: 99%

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Lee

Dick

2011

Eye

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The blockbuster drug paradigm is under increasing scrutiny across the biopharmaceutical industry. Intraocular inflammation poses particular challenges to this, given the heterogeneity of conditions in the uveitis spectrum, and the increasing acknowledgement of individual patient and disease variance in underlying immune responses. This need has triggered a drive towards personalised and stratified medicine, supported and enabled as a result of continued development of both experimental models and molecular biological techniques and improved clinical classification. As such we have the ability now to systematically appraise at a genomic, transcriptomic, and proteomic level individual immunophenotype, and the promise that in the eye this can be augmented by in vivo immune imaging to identify individual immunopathology. With such advances all running in parallel, we are entering an era of experimental medicine that will facilitate early diagnosis, generate biomarkers for accurate prognostication, and enable the development of individualised and targeted therapies, which can progress rapidly into clinical practice.

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Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome

Abstract: Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS. (ClinicalTrials.gov number, NCT00465985.)

Cited by 779 publications

References 14 publications

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

An Expanding Role for Interleukin-1 Blockade from Gout to Cancer

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

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