Emerging systemic drugs in the treatment of plaque psoriasis

Balogh, Esther A.; Bashyam, Arjun M.; Ghamrawi, Rima I.; Feldman, Steven R.

doi:10.1080/14728214.2020.1745773

Cited by 33 publications

(32 citation statements)

References 46 publications

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“…Plaque psoriasis clinically manifests with erythematous, asymmetric and thick plaques, mostly affecting the arms, trunk, and scalp. A smaller percentage of patients shows additional clinical forms of the disease, including erythrodermic, pustular, guttate, inverse, and palmoplantar psoriasis [105]. An increased risk of cardiovascular diseases has been also described.…”

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

“…Thus, psoriasis bears a significant personal and social burden and, despite the current availability of several oral and topic treatments, many patients have not found a real relief yet. This is mostly due to side effects, the high cost of the therapy, and poor patient compliance due to the route of administration [105]. More than 40 genetic mutations have been correlated with psoriasis, and it is now currently recognized that the pathology becomes manifested when a genetically predisposed individual is exposed to environmental triggers (e.g., stress, infection, trauma, or even some medications).…”

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

“…Based on current knowledge, activated dendritic cells in the dermis act as triggers for the pathology through the increased production of IL-23, which in turn promotes IL-17 production by dysregulated CD4+ T cells (Th17 cells), innate lymphoid cells, and γδ T cells. Pathological T cells migrate to the epidermis and modify keratinocytes functions leading to the appearance of the classical psoriasis lesions [105]. Based on the key role played by A 3 ARs in controlling immune cell function and on the positive results in RA (see above), CF101 has been proposed as an innovative anti-psoriasis treatment.…”

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

“…Based on the key role played by A 3 ARs in controlling immune cell function and on the positive results in RA (see above), CF101 has been proposed as an innovative anti-psoriasis treatment. Results from Phase II clinical trials have been so encouraging (with 35.3% of patients reaching an amelioration of the Psoriasis Area and Severity Index, PASI, of 50%, and two additional subjects of 73% and 100%), and side effects so limited (with an incidence of 17.6% in the group treated with the most effective dose of the drug, i.e., 2 mg, compared to 21.1% in the placebo group), that the drug has entered a currently ongoing Phase III clinical study [105].…”

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

“…Closely related to psoriasis, psoriatic arthritis is an inflammatory musculoskeletal disease that affects approximately one-third of patients who already have psoriasis, and which can present as oligoarthritis, enthesitis, and dactylitis, as well as psoriatic nail disease [105]. In recent years, it has been demonstrated that TNF-α represents one crucial element in the development of psoriatic arthritis, and both direct and receptor TNF-α inhibitors are currently utilized as well-tolerated pharmacological treatments [106].…”

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

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Adenosine Signaling in Autoimmune Disorders

Magni

Ceruti

2020

Pharmaceuticals

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The molecular components of the purinergic system (i.e., receptors, metabolizing enzymes and membrane transporters) are widely expressed in the cells of the immune system. Additionally, high concentrations of adenosine are generated from the hydrolysis of ATP in any “danger” condition, when oxygen and energy availability dramatically drops. Therefore, adenosine acts as a retaliatory metabolite to counteract the nucleotide-mediated boost of the immune reaction. Based on this observation, it can be foreseen that the recruitment with selective agonists of the receptors involved in the immunomodulatory effect of adenosine might represent an innovative anti-inflammatory approach with potential exploitation in autoimmune disorders. Quite surprisingly, pro-inflammatory activity exerted by some adenosine receptors has been also identified, thus paving the way for the hypothesis that at least some autoimmune disorders may be caused by a derailment of adenosine signaling. In this review article, we provide a general overview of the roles played by adenosine on immune cells with a specific focus on the development of adenosine-based therapies for autoimmune disorders, as demonstrated by the exciting data from concluded and ongoing clinical trials.

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Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

Section: A 3 Ar Agonists: Clinical Trials Are Already On Their Way Tomentioning

confidence: 99%

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Adenosine Signaling in Autoimmune Disorders

Magni

Ceruti

2020

Pharmaceuticals

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Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors

Chimalakonda

Burke

Cheng

et al. 2021

Dermatol Ther (Heidelb)

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Introduction: Deucravacitinib, a novel, oral, selective inhibitor of tyrosine kinase 2 (TYK2) signaling, acts via an allosteric mechanism by binding to the enzyme's regulatory domain instead of the catalytic domain. This unique binding provides high functional selectivity for TYK2 versus the closely related Janus kinases (JAKs) 1/2/3. Deucravacitinib was efficacious in phase 2 and 3 psoriasis trials, without clinical or laboratory parameters indicative of JAK 1/2/3 inhibition being observed. This analysis compared the kinase specificities of deucravacitinib versus JAK 1/2/3 inhibitors at therapeutic exposures.Methods: Signaling via JAK 1/3, JAK 2/2, and TYK2/JAK 2 dimers was measured in in vitro whole blood assays. Concentrations providing half-maximal inhibition (IC 50 ) in these assays were determined for deucravacitinib and the JAK 1/2/3 inhibitors tofacitinib, upadacitinib, and baricitinib. Newly derived whole blood IC 50 values were plotted against available pharmacokinetic profiles using doses evaluated in phase 2/3 trials. Simulated average daily inhibition and durations over which concentrations exceeded IC 50 were evaluated. Results: At clinically relevant exposures, projected steady-state deucravacitinib plasma concentrations were higher than TYK2 IC 50 for approximately 9-18 h. Maximal plasma concentrations (C max ) of deucravacitinib were 8-to James Burke: employee at the time the analysis was conducted.

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Dimethyl Fumarate's Effectiveness and Safety in Psoriasis: A Real-Life Experience During the COVID-19 Pandemic

Esposito

Campanati

Giunta

et al. 2022

Dermatol Ther (Heidelb)

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Introduction Dimethyl fumarate (DMF) is approved as oral systemic treatment for moderate-to-severe psoriasis. Scarce evidence is available for DMF treatment in psoriatic patients at the time of COVID-19 pandemic. The objective of this study was to assess the long-term effectiveness and safety of DMF monotherapy in moderate-to-severe psoriasis during the COVID-19 pandemic period. Methods This multicenter, retrospective study included patients with moderate-to-severe psoriasis who had received a 48-week DMF treatment during the COVID-19 pandemic. Selected outcomes were: variation of mean PASI, proportion of patients achieving PASI50 and PASI75, variation of mean PGA and face PGA, genital PGA, scalp PGA, mean itch VAS and mean DLQI. Results Forty-four patients were enrolled, and four patients became COVID-19 positive during the observation period but did not discontinue DMF therapy. DMF produced a significant improvement of signs and symptoms of psoriasis as expressed by mean PASI variation from 13.07 at baseline to 6.11 at week 48 ( p < 0.0001), itch VAS from 3.22 at baseline to 1.18 at week 48 ( p < 0.001), PGA from 2.84 at baseline to 1.30 at week 48 ( p < 0.0001) and DLQI from 13.09 at baseline to 6.07 at week 48 ( p < 0.0001). The percentage of patients who achieved PASI50 and PASI75 was 4.55% at week 4 and 59.09% at week 48 and 0% at week 4 and 22.73% at week 48, respectively. A clinical important decrease of mean PGA score was observed in all subgroups, face psoriasis, genital psoriasis and scalp psoriasis. Adverse events were predictable and manageable. Conclusions DMF monotherapy is an effective and safe treatment option in moderate-to-severe psoriasis also in patients who develop SARS-CoV-2 infection.

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Emerging systemic drugs in the treatment of plaque psoriasis

Cited by 33 publications

References 46 publications

Adenosine Signaling in Autoimmune Disorders

Adenosine Signaling in Autoimmune Disorders

Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors

Dimethyl Fumarate's Effectiveness and Safety in Psoriasis: A Real-Life Experience During the COVID-19 Pandemic

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