Effects of Apremilast on Pruritus and Skin Discomfort/Pain Correlate With Improvements in Quality of Life in Patients With Moderate to Severe Plaque Psoriasis

Sobell, Jeffrey M.; Foley, Peter; Toth, Darryl; Mrowietz, Ulrich; Girolomoni, Giampiero; Gonçalves, Joana; Day, Robert M.; Chen, Rongdean; Yosipovitch, Gil

doi:10.2340/00015555-2360

Cited by 55 publications

(34 citation statements)

References 33 publications

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“…Such clinical data may form an important foundation to support the evidence‐based care of psoriasis patients with itch symptoms. The following discussion reviews the itch effect of topical agents, systemics and biologics, and phototherapy, as revealed in recent studies (Table ) . Itch relief remains a significant gap in the treatment landscape for psoriasis, as not all patients are able to achieve control of this symptom, even with cleared or markedly improved skin.…”

Section: Management Of Itch In Psoriasismentioning

confidence: 99%

Itch: an under‐recognized problem in psoriasis

Elewski

Alexis

Lebwohl

et al. 2019

Acad Dermatol Venereol

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Psoriasis has historically been considered a nonpruritic dermatosis, in contrast with atopic dermatitis. Thus, itch has often been underappreciated and overlooked in psoriasis. However, increasing evidence over the past decade has shown that itch can be one of the most prevalent and burdensome symptoms associated with psoriasis, affecting almost every patient to some degree. Itch can involve the entire body, although it predominantly affects the legs, hands, back, body and especially the scalp. Uncontrolled itch can significantly impact all aspects of the well‐being and quality of life of the patient. While there has been some progress in trying to better understand the pathophysiology of itch in psoriasis, more research effort and interest are needed. This under‐recognition of itch in psoriasis is clearly reflected in the dearth of treatment options targeting itch despite significant advancement in treating the lesions themselves. Recently, however, clinical studies have begun to include itch as a study outcome. The resulting data have demonstrated concomitant antipruritic benefits and improved Psoriasis Area and Severity Index (PASI) scores with mainstay treatments for psoriasis, such as topical corticosteroids and vitamin D analogs, phototherapies, and various systemics and biologics. This article takes a closer look at this debilitating symptom, reviewing the available epidemiology data for psoriatic itch, presenting the current understanding of psoriatic itch pathophysiology and highlighting important clinical data for various treatment options for itch. Practical considerations for increasing the recognition of itch as well as improving its management in psoriasis are also provided.

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Section: Management Of Itch In Psoriasismentioning

confidence: 99%

Itch: an under‐recognized problem in psoriasis

Elewski

Alexis

Lebwohl

et al. 2019

Acad Dermatol Venereol

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“…The key underlying motor manifestation is caused by a slow and progressive degeneration of dopamine‐producing neurons in the substantia nigra . Parkinson's disease affects 7 to 10 million persons worldwide, making it the second most prevalent neurodegenerative disorder after Alzheimer's disease . Parkinson's disease is also associated with significant economic burden; in 2010, in the United States, medical expenses related to Parkinson's disease were approximately 2‐fold higher than they were for an age‐matched population without Parkinson's disease …”

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confidence: 99%

First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers

et al. 2016

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Background: α‐Synuclein is a major component of pathologic inclusions that characterize Parkinson's disease. PRX002 is an antibody that targets α‐synuclein, and its murine parent antibody 9E4 has been shown in preclinical studies to reduce α‐synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration in human α‐synuclein transgenic mice. Methods: This first‐in‐human, randomized, double‐blind, placebo‐controlled, phase 1 study assessed the impact of PRX002 administered to 40 healthy participants in 5 ascending‐dose cohorts (n = 8/cohort) in which participants were randomly assigned to receive a single intravenous infusion of study drug (0.3, 1, 3, 10, or 30 mg/kg; n = 6/cohort) or placebo (n = 2/cohort). Results: PRX002 demonstrated favorable safety, tolerability, and pharmacokinetic profiles at all doses tested, with no immunogenicity. No serious adverse events, discontinuations as a result of adverse events, or dose‐limiting toxicities were reported. Serum PRX002 exposure was dose proportional; the average terminal half‐life across all doses was 18.2 days. A significant dose‐dependent reduction in free serum α‐synuclein (unbound to PRX002) was apparent within 1 hour after PRX002 administration, whereas total α‐synuclein (free plus bound) increased dose‐dependently, presumably because of the expected change in kinetics following antibody binding. Conclusions: This study demonstrates that serum α‐synuclein can be safely modulated in a dose‐dependent manner after single intravenous infusions of an anti–α‐synuclein antibody. These findings support continued development of PRX002, including further characterization of its safety, tolerability, pharmacokinetics, and pharmacodynamic effects in the central nervous system in patients with Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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“…A recent analysis of the ESTEEM 1 and 2 studies found that apremilast provided rapid and sustained improvement in pruritus and skin discomfort/pain, symptoms not typically captured in psoriasis assessments (e.g. PASI) that contribute significantly to patients’ disease severity and HRQOL perceptions . For example, a significant ( P < 0.001) positive correlation existed between mean changes from baseline in pruritus VAS and DLQI total scores among patients receiving apremilast at Week 16, which was maintained at Week 32 …”

Section: Discussionmentioning

confidence: 99%

Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient‐reported outcomes in the treatment of moderate to severe psoriasis: results of two phase III randomized, controlled trials

Thaçi

Kimball

Foley

et al. 2016

Acad Dermatol Venereol

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BackgroundApremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis.ObjectivesTo evaluate the impact of apremilast on health‐related quality of life (HRQOL), general functioning and mental health using patient‐reported outcome (PRO) assessments among patients with moderate to severe plaque psoriasis in the ESTEEM 1 and 2 trials.MethodsA total of 1255 patients were randomized (2 : 1) to apremilast 30 mg BID or placebo for 16 weeks; all received apremilast through Week 32. PRO assessments included the Dermatology Life Quality Index (DLQI), 36‐Item Short‐Form Health Survey version 2 mental/physical component summary scores (SF‐36v2 MCS/PCS), Patient Health Questionnaire‐8 (PHQ‐8), EuroQol‐5D (EQ‐5D) and Work Limitations Questionnaire‐25 (WLQ‐25). Post hoc analyses examined relationships between Psoriasis Area and Severity Index (PASI) scores and PHQ‐8 in the apremilast‐treated population at Week 16.ResultsTreatment with apremilast improved all HRQOL PROs at Week 16 (vs. placebo), except the SF‐36v2 PCS, and improvements were sustained through Week 32. Mean DLQI and SF‐36v2 MCS improvements exceeded minimal clinically important differences. Changes at Week 16 in PHQ‐8 and PASI were weakly correlated, and only 35.8% of patients who achieved a ≥75% reduction from baseline in PASI score (PASI‐75) with apremilast treatment also achieved PHQ‐8 scores of 0–4.ConclusionsApremilast led to improvements in HRQOL PROs vs. placebo in patients with moderate to severe plaque psoriasis.

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Effects of Apremilast on Pruritus and Skin Discomfort/Pain Correlate With Improvements in Quality of Life in Patients With Moderate to Severe Plaque Psoriasis

Cited by 55 publications

References 33 publications

Itch: an under‐recognized problem in psoriasis

Itch: an under‐recognized problem in psoriasis

First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers

Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient‐reported outcomes in the treatment of moderate to severe psoriasis: results of two phase III randomized, controlled trials

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