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Article ; Online: Oral therapies for psoriasis and psoriatic arthritis: current knowledge and future perspectives.

Torres, Tiago

Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia

2020 Volume 155, Issue 4, Page(s) 384–385

MeSH term(s)	Administration, Oral ; Arthritis, Psoriatic/drug therapy ; Forecasting ; Humans ; Psoriasis/drug therapy
Language	English
Publishing date	2020-06-15
Publishing country	Italy
Document type	Editorial
ZDB-ID	604114-0
ISSN	1827-1820 ; 0026-4741 ; 0392-0488
ISSN (online)	1827-1820
ISSN	0026-4741 ; 0392-0488
DOI	10.23736/S0392-0488.20.06712-7
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Article ; Online: Difamilast for the treatment of atopic dermatitis.

Freitas, Egídio / Torres, Tiago

The Journal of international medical research

2023 Volume 51, Issue 6, Page(s) 3000605231169445

Abstract: Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is ... ...

Abstract	Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is associated with long-term efficacy and safety issues. Therefore, new topical therapies with different mechanisms of action are required to overcome the limitations of existing treatments. Difamilast is a phosphodiesterase 4 inhibitor currently in phase 3 studies. Difamilast shows antipruritic and anti-inflammatory properties and a rapid onset of action, with significant differences in some parameters from the vehicle within 1 week of treatment. Phase 2 and 3 clinical trials have shown that difamilast ointments are effective and well tolerated in adult and pediatric patients with AD, and are expected to be used for long-term AD treatment. In 2021, difamilast was the first phosphodiesterase 4inhibitor to acquire manufacturing and marketing approval in Japan for the treatment of adult and pediatric patients (2 years of age and older) with AD. This article is a narrative review of the current literature on difamilast in the management of AD.
MeSH term(s)	Adult ; Humans ; Child ; Dermatitis, Atopic/drug therapy ; Skin ; Benzamides ; Commerce
Chemical Substances	difamilast (T3U32GLJ0F) ; Benzamides
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/03000605231169445
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Article ; Online: New molecules for atopic dermatitis treatment beyond biological therapy.

Freitas, Egídio / Torres, Tiago

Current opinion in allergy and clinical immunology

2023 Volume 23, Issue 3, Page(s) 210–215

Abstract: Purpose of review: This review aims to provide a summary of current knowledge on new topical and oral non-biological therapies recently approved for Atopic Dermatitis (AD) treatment.: Recent findings: The immense research carried out in the last ... ...

Abstract	Purpose of review: This review aims to provide a summary of current knowledge on new topical and oral non-biological therapies recently approved for Atopic Dermatitis (AD) treatment. Recent findings: The immense research carried out in the last decade has focused on understanding the molecular basis underlying AD and has allowed the development of new targeted drugs. Despite several biologic therapies are approved or in development, other non-biologic targeted therapies (small molecules) have emerged, such as the Janus kinase (JAK) inhibitors baricitinib, upadacitinib and abrocitinib, expanding the range of therapeutic options. Based on recent available data from head-to-head comparisons and meta-analysis studies, JAK inhibitors showed a faster onset of action and slightly higher efficacy at 16 weeks compared with biologic agents. Concerning topical treatment, presently, corticosteroids and calcineurin inhibitors are the main therapeutic options, but are not recommended for long-term management due to potential safety issues. Currently, two topical JAK inhibitors (ruxolitinib and delgocitinib) and one phosphodiesterase 4 (PDE4) inhibitor (difamilast) are approved and have shown good efficacy results and a favorable safety profile. Summary: These new drugs (systemic and topical) are needed to increase the success of AD treatment, particularly for patients who do not or no longer respond to treatment.
MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Janus Kinase Inhibitors/therapeutic use ; Administration, Topical ; Biological Therapy ; Phosphodiesterase 4 Inhibitors/therapeutic use
Chemical Substances	Janus Kinase Inhibitors ; Phosphodiesterase 4 Inhibitors
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Review ; Meta-Analysis ; Journal Article
ZDB-ID	2088710-3
ISSN	1473-6322 ; 1528-4050
ISSN (online)	1473-6322
ISSN	1528-4050
DOI	10.1097/ACI.0000000000000910
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Article: Emerging Oral Therapies for the Treatment of Psoriasis: A Review of Pipeline Agents.

Drakos, Anastasia / Torres, Tiago / Vender, Ronald

Pharmaceutics

2024 Volume 16, Issue 1

Abstract: The introduction of biologic agents for the treatment of psoriasis has revolutionized the current treatment landscape, targeting cytokines in the interleukin (IL)-23/IL-17 pathway and demonstrating strong efficacy and safety profiles in clinical trials. ... ...

Abstract	The introduction of biologic agents for the treatment of psoriasis has revolutionized the current treatment landscape, targeting cytokines in the interleukin (IL)-23/IL-17 pathway and demonstrating strong efficacy and safety profiles in clinical trials. These agents however are costly, are associated with a risk of immunogenicity, and require administration by intravenous or subcutaneous injection, limiting their use among patients. Oral therapies, specifically small molecule and microbiome therapeutics, have the potential to be more convenient and cost-effective agents for patients and have been a focus of development in recent years, with few targeted oral medications available for the disease. In this manuscript, we review pipeline oral therapies for psoriasis identified through a search of ClinicalTrials.gov (30 June 2022-1 October 2023). Available preclinical and clinical trial data on each therapeutic agent are discussed. Small molecules under development include tumor necrosis factor inhibitors, IL-23 inhibitors, IL-17 inhibitors, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, A3 adenosine receptor agonists, and sphingosine-1-phosphate receptor 1 agonists, several of which are entering phase III trials. Oral microbials have also demonstrated success in early phase studies. As new oral therapies emerge for the treatment of psoriasis, real-world data and comparative trials are needed to better inform their use among patients.
Language	English
Publishing date	2024-01-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics16010111
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Article ; Online: Risankizumab, a therapeutic alternative for psoriasis in people living with HIV.

Estevinho, Tomás / Freitas, Egídio / Torres, Tiago

The Journal of international medical research

2024 Volume 52, Issue 3, Page(s) 3000605241229324

Abstract: The management of psoriasis in individuals with human immunodeficiency virus (HIV) presents a unique challenge, marked by a more severe progression and limited efficacy of first- and second-line treatments. Although conventional systemic therapies might ... ...

Abstract	The management of psoriasis in individuals with human immunodeficiency virus (HIV) presents a unique challenge, marked by a more severe progression and limited efficacy of first- and second-line treatments. Although conventional systemic therapies might be considered, these agents are immunosuppressants, making their use challenging in people living with HIV (PLHIV). Biologic agents are frequently used in individuals with moderate-to-severe psoriasis, but their efficacy and safety data in PLHIV are very limited, as this patient group tends to be excluded from clinical trials. Risankizumab is a selective interleukin-23 (IL-23) inhibitor that has demonstrated a favourable safety profile and high efficacy in long-term studies and clinical practice. This current case report presents two clinical cases of PLHIV with plaque psoriasis who were effectively treated with the biologic agent risankizumab, with no reported safety issues. Although there are limited data on the use of biologics in PLHIV, this case series suggests that IL-23 inhibitors, namely risankizumab, might be a valuable therapeutic option for this population. Additional research and larger studies are needed to gain a more comprehensive understanding of the long-term safety and efficacy of IL-23 inhibitors in individuals affected by HIV.
MeSH term(s)	Humans ; HIV ; Interleukin-23 ; Psoriasis/complications ; Psoriasis/drug therapy ; HIV Infections/complications ; HIV Infections/drug therapy ; Antibodies, Monoclonal
Chemical Substances	risankizumab (90ZX3Q3FR7) ; Interleukin-23 ; Antibodies, Monoclonal
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/03000605241229324
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Article ; Online: Correction to: New Topical Therapies for Psoriasis.

Lé, Ana Maria / Torres, Tiago

American journal of clinical dermatology

2022 Volume 23, Issue 1, Page(s) 25

Language	English
Publishing date	2022-01-18
Publishing country	New Zealand
Document type	Published Erratum
ZDB-ID	1502476-3
ISSN	1179-1888 ; 1175-0561
ISSN (online)	1179-1888
ISSN	1175-0561
DOI	10.1007/s40257-021-00657-w
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Article: OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis-Focus on Rocatinlimab and Amlitelimab.

Lé, Ana Maria / Torres, Tiago

Pharmaceutics

2022 Volume 14, Issue 12

Abstract: Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic ... ...

Abstract	Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic dermatitis. OX40 and OX40L are two checkpoint molecules that bind to potentiate pro-inflammatory T-cell responses that are pivotal to atopic dermatitis pathogenesis. Two OX40-OX40L inhibitors, rocatinlimab and amlitelimab, are being developed for the treatment of atopic dermatitis. Rocatinlimab, an anti-OX40 antibody, was evaluated in phase 2b, a randomized, placebo-controlled clinical trial. At week 16, rocatinlimab groups achieved a greater reduction in the EASI percentage change from the baseline (−48.3% to −61.1%) against the placebo (−15.0%; p < 0.001), and clinical response was maintained 20 weeks after the treatment had ceased. Amlitelimab, an anti-OX40L antibody, was studied in a 12-week treatment phase 2a clinical trial, with a significant efficacy response observed within 2 weeks. At week 16, amlitelimab groups reached the EASI mean percentage change from the baseline of −69.9% and −80.1% versus the placebo (−49.4%; p = 0.072 and p = 0.009). Among the responders, 68% of amlitelimab patients were sustained 24 weeks following the last dose. Both treatments were shown to be safe and well tolerated. Current evidence points to OX40-OX40L inhibitors as future options for atopic dermatitis treatment with potential disease-modifying effects.
Language	English
Publishing date	2022-12-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14122753
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Article: Upadacitinib for the treatment of psoriatic arthritis.

Fonseca, Diogo / Nogueira, Miguel / Torres, Tiago

Drugs in context

2023 Volume 12

Abstract: Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of ... ...

Abstract	Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules. The results obtained in the phase III clinical trials (SELECT-PsA 1 and SELEC-PsA 2) demonstrated that upadacitinib was highly effective over placebo and non-inferior to adalimumab in several important domains of the disease. Improvements were observed in dactylitis, enthesitis and spondylitis as well as in physical function, pain, fatigue and overall quality of life. The safety profile of these results resembled that of adalimumab, apart from a slightly higher rate of herpes zoster infection, an increase of creatine kinase and an incidence of lymphopenia. However, none of these events was considered a serious adverse advent. Additionally, another analysis demonstrated that combining upadacitinib with methotrexate was associated with a similar efficacy to upadacitinib in monotherapy, both for patients that are naive to biologics treatment and for those previously treated with biologics. Therefore, upadacitinib is a new option for the treatment of psoriatic arthritis, presenting a series of beneficial characteristics. At this stage, it is important to collect long-term data to confirm the efficacy and safety profiles shown in clinical trials.
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2719560-0
ISSN	1740-4398 ; 1745-1981
ISSN (online)	1740-4398
ISSN	1745-1981
DOI	10.7573/dic.2022-11-6
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Article: Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.

Martins, Ana / Lé, Ana Maria / Torres, Tiago

Drugs in context

2023 Volume 12

Abstract: Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay ... ...

Abstract	Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay between an individual's genotype and environmental factors that triggers an immune response and leads to the production of a cytokine cascade. Even though there are about 17 targeted therapies for PsA, a significant percentage of patients fail to respond to such treatments, have a partial response or develop side-effects. This article aims to review the current knowledge on deucravacitinib, a new oral small molecule that selectively inhibits tyrosine kinase 2 (TYK2), for the treatment of PsA. TYK2, a member of the Janus kinase (JAK) family, is responsible for mediating intracellular signalling of cytokines involved in the pathogenesis of PsA and psoriasis, namely IL-12, IL-23, and type I interferons. Recently, deucravacitinib was approved by the FDA for the treatment of moderate-to-severe plaque psoriasis and is currently being evaluated in phase III clinical trials in PsA. In a phase II clinical trial, deucravacitinib showed sustained effectiveness in several domains of PsA, namely arthritis, enthesitis and dactylitis, was well tolerated, and had a favourable safety profile. In patients with psoriasis, deucravacitinib had shown a higher efficacy than placebo and apremilast. Deucravacitinib is a promising therapy, with a unique mechanism of action. Results from the phase III programme and studies evaluating long-term response and head-to-head comparisons with other targeted agents will be important to establishing the position of deucravacitinib in the management of PsA.
Language	English
Publishing date	2023-05-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2719560-0
ISSN	1740-4398 ; 1745-1981
ISSN (online)	1740-4398
ISSN	1745-1981
DOI	10.7573/dic.2023-2-7
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Article: Efficacy and safety of baricitinib in patients with alopecia areata: evidence to date.

Faria, Sofia / Freitas, Egídio / Torres, Tiago

Drugs in context

2023 Volume 12

Abstract: Alopecia areata (AA) is a chronic, tissue-specific autoimmune disorder, characterized by non-scaring hair loss, with a global prevalence of approximately 2%. Typically, it affects a young population, with initial onset frequently occurring before the age ...

Abstract	Alopecia areata (AA) is a chronic, tissue-specific autoimmune disorder, characterized by non-scaring hair loss, with a global prevalence of approximately 2%. Typically, it affects a young population, with initial onset frequently occurring before the age of 30 years. Even though the exact pathogenesis of AA remains unclear, the predominant hypothesis is the breakdown of immune privilege of the hair follicle, resulting in increased self-antigen and major histocompatibility complex expression in the follicular epithelium. The relapsing nature of the disease negatively impacts patients' quality of life and makes them more susceptible to developing psychiatric comorbidities. Although many treatment modalities have been proposed, there are no currently available treatments able to induce and sustain disease remission. Traditional treatment modalities, despite being widely used, present limited results and a high risk of adverse effects. Hence, there exists an unfulfilled requirement for treatments that are both more efficient and safer. The latest understanding of the pathophysiology of AA and its connection to the JAK-STAT pathway has prompted the advancement of JAK inhibitors. These small-molecule agents function by obstructing the JAK-STAT intracellular signalling pathway. Baricitinib an orally administered, selective JAK1 and JAK2 inhibitor is a promising alternative to the available treatments, and is already approved for the treatment of AA.
Language	English
Publishing date	2023-09-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2719560-0
ISSN	1740-4398 ; 1745-1981
ISSN (online)	1740-4398
ISSN	1745-1981
DOI	10.7573/dic.2023-6-2
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