The efficacy of multiple courses of alefacept in patients with moderate to severe chronic plaque psoriasis

Menter, Alan; Cather, Jennifer Clay; Baker, Diane R.; Farber, Harold F.; Lebwohl, Mark; Darif, Mohamed

doi:10.1016/j.jaad.2005.10.006

Cited by 48 publications

(42 citation statements)

References 9 publications

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“…While a large proportion of cases of AWP have been found in patients with CF, it has also been reported to be associated with marasmus [1] and with certain medications including cyclo-oxygenase 2 (COX-2) inhibitors [14,15,16] and aminoglycoside antibiotics [17]. …”

Section: Introductionmentioning

confidence: 99%

“…More recently it has been hypothesised that the aetiology may be in part due to ineffective regulation of cell volume by the calcium-dependent transient receptor potential (TRP) mechanosensitive receptors. Swelling-activated calcium entry via theTRPV4 channel has been shown to be defective in CF epithelia, and the same channel is postulated to be defective in CF keratinocytes [17]. …”

Section: Introductionmentioning

confidence: 99%

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Aquagenic Wrinkling of the Palms in an Adult Cystic Fibrosis Population

Tolland

Boyle²,

Hall³

et al. 2010

Dermatology

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Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterised by the development of oedema and excessive wrinkling of the palms following exposure to water. It has frequently been associated with cystic fibrosis (CF). Early reports of AWP have only been case reports or small case series; there has only been one reported prevalence study of AWP in a CF population. Objective: To determine the incidence and characteristics of AWP in the adult CF population in Northern Ireland. Methods: 105 CF patients were interviewed. The patients were asked whether they noticed excess wrinkling of the hands when exposed to water. If they answered ‘yes’, further questions were asked regarding clinical characteristics. The atopic status, CF genotype and drug history were recorded for each patient. Formal testing of 7 patients was carried out. Results: Out of the 105 patients who were interviewed, 43 (41%) described AWP. Of the 43 patients with AWP, 20 were male and 23 were female. There was no association of AWP with genotype, atopy or concomitant drug intake. Conclusion: AWP appears to have an equal sex incidence, and the high number of cases in the population studied would suggest that this condition is underreported.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aquagenic Wrinkling of the Palms in an Adult Cystic Fibrosis Population

Tolland

Boyle²,

Hall³

et al. 2010

Dermatology

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“…In addition, alefacept has several advantages as a tool for decreasing HIV reservoir; this biologic can be used transiently to facilitate significant reduction of the CD2 hi CD4 + T cell pool with no impairment of primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen [76]. Moreover, single or multiple dosing regimens can be used safely as was done in psoriasis clinical trials [19,[77][78][79].…”

Section: Proposal: Use Of Alefacept In Reducing Hiv Reservoir By Nk Cmentioning

confidence: 99%

Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

Zaidi¹,

Meng²

2016

Immunother Open Acc

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Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4 + T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cellmediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2 hi memory CD4 + T cells are a significant contributor.

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“…Other studies have been performed to investigate alefacept efficacy and safety in the long-term treatment of plaque psoriasis. Treatment of up to 5 courses provided incremental efficacy in responders, while maintaining the safety profile (Menter et al, 2006;Roberts et al, 2010). Although these studies are limited by the decreasing number of patients over multiple treatment courses or the lack of appropriate controls, but do they suggest that multiple courses of alefacept are well tolerated and maintain clinical improvement in responder patients.…”

Section: Clinical Efficacymentioning

confidence: 99%