A Novel Halobetasol Propionate 0.01%/Tazarotene 0.045% Fixed Combination Treatment for Psoriasis

Radonjic, Aleksandar; Evans, Emily L

doi:10.1111/dth.12979

“…For instance, the topical agent Tazarotene, and oral agent Acitretin (and its predecessor Etretinate), are compounds largely used in the treatment of psoriatic plaques 59,60 . Tazarotene is a retinoid drug which has been approved in 2019 from Food and Drug Administration (FDA) in combination with Halobetasol in PSO affected adults 61 . On the other hand, Acitretin is used in severe psoriatic manifestations, but due to its high lipophilic capacity shows teratogenic effects and it is contra-indicated in pregnancy and for 3 years prior to conception 62 .…”

Section: Discussionmentioning

confidence: 99%

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

Federico

¹

,

Pavel

²

,

Moebus

³

et al. 2021

Preprint

1

0

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In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we collected, curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks. The integrated transcriptomics analysis of public datasets shed light on a number of genes which are frequently deregulated in the psoriatic lesion compared with the unaffected skin in a large number of studies. In particular, CRABP2, LCN2, S100A12 and PDZK1IP1 were found to be deregulated in all of the datasets analyzed. Furthermore, the analysis of co-expression networks highlights genes showing aberrant patterns of connectivity in the lesional network as compared to the network inferred from unaffected skin samples. For instance, we identified co-expression patterns of SERPINB4, KYNU and S100A12 as being the most affected by the disease. Network analysis allowed us to identify YPEL1 and HUS1 as plausible, previously unknown, actors in the expression of the psoriasis phenotype. In addition, by exploiting topological properties of the network models, we highlighted a set of 250 non-deregulated genes, 223 of which have never been associated with the disease before, including CACNA1A, HADH, ATP5MC1 and CBARP among others. Finally, we characterized specific communities of co-expressed genes sustaining relevant molecular functions and specific immune cell types expression signatures playing a role in the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.

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“…In longer-term studies, however, HP/TAZ discontinuation rates resulting from adverse events were similar to those of retinoid-only treatment groups. 12,23 Additional side effects of the HP/TAZ combination include increased risk of photosensitivity, subcapsular cataracts, and glaucoma, reflecting previously established side effects of corticosteroids and retinoids. 27 Contraindications HP/TAZ contains a vitamin A derivative from the TAZ component and is contraindicated in pregnant patients and women of reproductive age not on adequate birth control.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…Its side effects include skin atrophy, leukoderma, folliculitis, telangiectasias, and possible suppression of the hypothalamic-pituitary-adrenal (HPA) axis. 12 TAZ, on the other hand, is a vitamin A derivative that improves psoriasis primarily via effects on keratinocyte differentiation. TAZ side effects include application site irritation.…”

Section: Introductionmentioning

confidence: 99%

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials

Ramachandran

¹

,

Bertus

²

,

Bashyam

³

et al. 2020

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Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.

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The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

Federico

¹

,

Pavel

²

,

Möbus

³

et al. 2022

View full text Add to dashboard Cite

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks. The integrated analysis of transcriptomics data and co-expression networks highlighted genes that are frequently dysregulated and show aberrant patterns of connectivity in the psoriatic lesion compared with the unaffected skin. Our approach allowed us to also identify plausible, previously unknown, actors in the expression of the psoriasis phenotype. Finally, we characterized communities of co-expressed genes associated with relevant molecular functions and expression signatures of specific immune cell types associated with the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.

show abstract

A Novel Halobetasol Propionate 0.01%/Tazarotene 0.045% Fixed Combination Treatment for Psoriasis

Cited by 3 publications

References 2 publications

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

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