Potential New Indications of Topical Calcineurin Inhibitors

Luger, Thomas A.; Paul, C.

doi:10.1159/000102119

Cited by 74 publications

(57 citation statements)

References 102 publications

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“…The therapeutic effectiveness of the Cn inhibitors (CnIs)-principally cyclosporin A (CsA) and tacrolimus-widely in use for the prevention of allograft rejection in transplantation patients (9 ) and for the treatment of inflammatory skin conditions (10,11 ) is based on their ability to suppress the immune system by inhibiting the synthesis of these proinflammatory and T cell-recruiting cytokines (12 ). Complexes of CsA and tacrolimus with carrier proteins known as "immunophilins" bind to Cn in such a man-ner that docking and dephosphorylation of NFAT is severely hampered (1 ).…”

confidence: 99%

Molecular Diagnostics of Calcineurin-Related Pathologies

Musson

Cobbaert²,

Smit³

2012

Clinical Chemistry

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BACKGROUND The Ca2+-dependent protein phosphatase enzyme calcineurin (Cn) (protein phosphatase 3) is best known for its role as director of the adaptive immune response. One of its principal substrates is the nuclear factor of activated T cells (NFAT), which translocates to the nucleus after dephosphorylation to mediate gene transcription. Drugs targeting Cn (the Cn inhibitors tacrolimus and cyclosporin A) have revolutionized posttransplantation therapy in allograft recipients by considerably reducing rejection rates. CONTENT Owing primarily to intensive study of the side effects of the Cn inhibitors, the unique importance of Cn and Cn/NFAT signaling in the normal physiological processes of many other cell and tissue types is becoming more evident. During the last decade, it has become clear that an extensive and diverse array of clinical conditions can be traced back, at least in part, to a disturbed Cn-signaling axis. Hence, both diagnostics and therapeutic monitoring could benefit from a technique that conveniently reads out Cn/NFAT operative status. SUMMARY This review outlines the current knowledge on the pathologic conditions that have calcineurin as a common denominator and reports on the progress that has been made toward successfully applying Cn and Cn/NFAT activity markers in molecular diagnostics.

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confidence: 99%

Molecular Diagnostics of Calcineurin-Related Pathologies

Musson

Cobbaert²,

Smit³

2012

Clinical Chemistry

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“…L'indication principale du tacrolimus est la prévention du rejet des allogreffes de rein, foie et coeur [6,7]. En dehors de cette indication figurant dans son autorisation de mise sur le marché, le tacrolimus topique a démontré son efficacité dans le traitement de nombreuses maladies inflammatoires dermatologiques cutanées et muqueuses comme l'eczéma ou la dermatite atopique [6,8].…”

Section: Discussionunclassified

Étude rétrospective de l’efficacité du Protopic® (tacrolimus) dans le traitement de la langue géographique algique

Haddad¹,

Boralévi

Catros³

et al. 2015

Med Buccale Chir Buccale

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Résumé -Introduction :La langue géographique (LG) est le plus souvent asymptomatique. Quand elle est douloureuse, le traitement est mal codifié. L'objectif de cette étude est d'évaluer l'efficacité du tacrolimus topique appliqué sur les LG algiques. Matériels et méthodes : Il s'agit d'une étude de cohorte descriptive, rétrospective, menée dans le service d'odontologie du CHU de Bordeaux de janvier 2012 à novembre 2013. Les patients sont traités par tacrolimus 0,1 % en application locale 2 fois par jour pendant 1 mois. Le critère de jugement principal est une évaluation de la douleur avec une échelle numérique verbale (ENV) de 0 à 10 à J0 et à 1 mois. Résultats : Trente et un patients ont consulté pour une langue géographique (LG). Sur ces 31 patients, 17 avaient des brûlures de la langue. Sur ces 17, 12 avaient une douleur imputable à la LG. Sur ces 12, 10 ont été traités par tacrolimus. Lors de la consultation initiale, l'ENV était de 5,9 +/-1,87. L'évaluation à un mois a montré une amélioration significative de l'ENV, 1,6 +/-1,5 (p < 0,001). Aucun événement indésirable grave n'est rapporté, seule une douleur oesophagienne est mentionnée chez trois patients. Conclusion : L'utilisation du tacrolimus topique semble efficace et bien tolérée dans l'indication d'une LG algique. Cependant, un essai randomisé versus placebo serait nécessaire afin de pouvoir conclure avec certitude. Abstract -Introduction:Geographic tongue is usually an asymptomatic disorder. There is no symptomatic treatment evaluated with clinical trials. Our objective was to evaluate the efficiency of tacrolimus in painful Geographic Tongue (GT). Methods: A retrospective descriptive cohort study was performed in the Department of Odontology PQR at the CHU in Bordeaux from January 2012 to November 2013. Patients with painful GT were treated with 0.1% tacrolimus (Protopic) topically twice a day for one month. The primary endpoint was the evaluation of pain with a numerical pain scale (NPS) from 0 to 10 the first day and one month later. The secondary endpoints were the improvement of the quality of life and of eating . Results: Thirty-one patients with GT consulted during the period studied. Seventeen had a burned tongue sensation, five patients presented primitive glossodynia and twelve had painful GT. Ten patients were treated with tacrolimus topically. The average value of the NPS was 5,9 (+/-1.87) at the first consultation. The GT lesions were present in all cases. Eating difficulties or a burned tongue sensation were described by patients. The evaluation one month after the prescription of Protopic showed a significant improvement of the NPS, with an average of 1,6 (+/-1.5) (t-test, p<0.001%). An improvement of the quality of life was noted for all patients. No serious adverse events were reported except esophagus pain for three patients. Conclusions: The utilization of topical tacrolimus seems to be efficient and well-tolerated in painful GT. However, randomized trials versus placebo are necessary to conclude with certitude.

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“…Hence, these agents have potential for treatment of skin diseases mediated by calcineurin phosphatase (Luger & Paul 2007). Currently these calcineurin inhibitors are approved for use in mild to moderate atopic dermatitis only, any use in psoriasis is off-label, and therefore not within approved US-FDA prescribing information.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

“…Tacrolimus ointment was approved in the United States in 2000, and Europe in 2001 for atopic dermatitis. However, new research has proven the potential use of tacrolimus in psoriasis (Luger & Paul 2007;Beck 2005). The introduction of tacrolimus ointment marked the advent of a new, nonsteroidal drug class, topical immunomodulators, for the management of inflammatory dermatoses.…”

Section: Tacrolimusmentioning

confidence: 99%