Brodalumab: 5-Year US Pharmacovigilance Report.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Brodalumab is an injectable treatment approved for moderate-to-severe plaque psoriasis in adults who lacked response to previous treatments. In the USA, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for increased suicidality risks; however, findings from 5 years of real-world safety data have demonstrated a lack of association. In this report, we discuss safety findings reported by US patients and healthcare providers for 4744 patients treated with brodalumab over 5 years. Joint pain (known as arthralgia) was the most common safety finding, with 122 cases reported over 5 years. Other safety findings of interest across 5 years included 106 serious infections (defined as prolonged infections or infections requiring treatment), 54 cases of depression, 49 cases of cancer (in 42 patients), 40 confirmed cases of COVID-19, and 11 cases of major cardiovascular events (such as stroke or heart attack). No completed suicides occurred throughout 5 years, and no new suicidal attempts were reported in year 5. In indirect comparisons with safety data from patients with psoriasis receiving or eligible to receive similar treatments, brodalumab was not associated with an increased risk of serious infection, cancer, major cardiovascular events, or inflammatory bowel disease. Taken together, these data are consistent with safety findings from long-term clinical trials and previous safety reports of brodalumab.

Integrating Precision Medicine into Medical Dermatology Clinical Practice: An Expert Consensus Panel.

BACKGROUND: Precision medicine utilizes an individual’s genomics to improve diagnosis, prognosis, and therapy. The joint American Academy of Dermatology and National Psoriasis Foundation 2019 guidelines recognized the need to identify biomarkers that can predict the optimal biologic agent for an individual patient. This paper examines the current state of precision medicine in dermatology and how its use can improve outcomes in psoriasis. METHODS: A search of PubMed/MEDLINE using the terms precision medicine, personalized medicine, biomarkers, genomics, and dermatology was performed to identify relevant publications. An expert consensus panel was then convened to assign levels of evidence to each article using strength of recommendation taxonomy and create consensus statements requiring a two-thirds supermajority for agreement utilizing a modified Delphi approach. RESULTS: Thirteen articles met inclusion and exclusion criteria and were assigned levels of evidence. The panel created 10 consensus statements on how precision medicine can improve patient outcomes, all of which received a unanimous (6/6) vote. CONCLUSION: Choosing a biologic medication for psoriasis often relies on patient preference, provider preference, and a trial-and-error approach. Utilizing precision medicine tests such as Mind.Px can help providers identify biomarkers unique to a patient’s pathophysiology and choose the optimal medication through a targeted and evidence-based approach. Zakria D, Brownstone N, Armstrong AW, et al. Integrating precision medicine into medical dermatology clinical practice: an expert consensus panel. J Drugs Dermatol. 2023;22(6):588-593. doi:10.36849/JDD.7432.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy.

INTRODUCTION: Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. METHODS: A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. RESULTS: A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA < 3%; p < .001). Patients with genitalia, nails, face, neck and scalp involvement had higher scores compared to patients without involvement (p < .001). CONCLUSIONS: Patients with more extensive disease and specific anatomical involvement experience a greater impact on intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.

Skin therapies: dermatologic perspective on the rheumatology-dermatology interface.

Psoriasis is a common, chronic, inflammatory skin condition in which up to 42% of patients may develop psoriatic arthritis. Consequently, dermatologists and rheumatologists frequently manage the same patient for psoriasis and psoriatic arthritis, respectively. Hence, it is important for the two specialties to understand one another and work together to optimise care of patients with psoriatic disease. This article discusses several areas of clinical concern in which coordination of care is especially critical. First, when selecting a therapeutic modality, it is best to use treatments that improve both the joints and the skin, and exercise caution while using options that can rarely worsen the skin, such as systemic steroids. Second, a close working relationship between the two specialties is critical in making prompt and early diagnosis of psoriatic arthritis. Dermatologists often are on the frontlines for detecting early signs of joint involvement, and the prevalence of undiagnosed PsA among patients with psoriasis is estimated to be 15.5%. Third, in the rare instance of anti-TNF induced paradoxical worsening of the skin disease, it is highly recommended that these patients be referred to dermatologists as soon as possible for optimal management of the skin manifestations. Lastly, dermatologists in the US have a long history of undertreating generalised psoriasis, especially with regards to the use of systemic agents. Therefore, the consideration of systemic agents by the rheumatologist may greatly benefit the patient by treating both the joint and skin manifestations. In summary, this article highlights the importance of interdisciplinary coordination between rheumatologists and dermatologists for which both specialties offer unique and complementary expertise to the care of patients with psoriatic disease.

What can U.S. dermatology learn from health care systems abroad? An observation of Taiwan's system of clinical efficiency as a possible model for increased patient access to care and affordability.

BACKGROUND: Difficulty in patient access to care and affordability are major problems faced by our dermatology specialty in the United States. However, Taiwan provides adequate and affordable dermatologic care for all of its citizens. Herein we describe our first-hand observations and findings of the outpatient dermatology experience in Taipei, and contrast it to the experience in the United States. OBSERVATION: In Taipei, Taiwan, we observed patient management, electronic documentation, and billing during outpatient dermatology visits in five settings: one academic hospital outpatient dermatology department, one academic hospital Information Technology department, and three private dermatologists' offices. Through our observations, we found that the dermatology specialty in Taiwan is able to overcome challenges with access to care and affordability through three key system features: (1) short yet frequent patient visits (2) close proximity of ancillary staff, and (3) an integrated and paperless electronic medical record and billing system. CONCLUSIONS: The Taiwan system is attained with some sacrifice, such as shorter time spent with patients and less personalized care. However, because this system can meet the basic dermatological needs of the entire population, possibly better than our current system, it behooves us to study the Taiwan system with respect and care.

Psychodermatology.

Psychodermatology is an underappreciated field that studies psychocutaneous disorders, which are conditions that have both dermatologic and psychiatric characteristics. Underlying psychiatric comorbidity is estimated to occur in up to one-third of dermatologic patients, and psychiatric illness may either be the cause or the consequence of dermatologic disease. Psychodermatologic patients lack insight and often do not recognize a psychiatric etiology for their symptoms and therefore comprise some of the most challenging cases to treat. Herein, we discuss the background and clinical presentation of the most commonly encountered psychodermatologic conditions, including delusional infestation, neurotic excoriations, factitial dermatitis, trichotillomania and body dysmorphic disorder, followed by practical diagnostic and therapeutic recommendations.

Delusions of parasitosis; suggested dialogue between dermatologist and patient.

Delusions of parasitosis (DoP) is a psychocutaneous condition characterized by a fixed false belief that one is infested by skin parasites. Patients afflicted with DoP generally experience sensations of biting, stinging or crawling in the absence of any objective evidence of infestation. The most definitive treatment for DoP is antipsychotic agents. Though the diagnosis and treatment options are rather straightforward, the difficulty lies in the art of building a therapeutic rapport with the patient in order to encourage acceptance of antipsychotic treatment. This article is a practical guide that suggests verbatim how dermatologists might talk to a delusional patient in order to establish a strong therapeutic rapport. Strategies on how to optimize the initial encounter, build rapport and prescribe antipsychotic medications that are likely to be accepted by the patient are discussed.

Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

BACKGROUND: The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. METHODS: In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. RESULTS: To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of "clear" or "almost clear". CONCLUSIONS: Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

Anti-IL-17 phase II data for psoriasis: A review.

UNLABELLED: Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p<0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.

Risk of systemic toxicity with topical lidocaine/prilocaine: a review.

The eutectic mixture of lidocaine and prilocaine (EMLA, APP Pharmaceuticals, LLC.) is an anesthetic cream frequently used by dermatologists. Although side effects of EMLA are usually mild local skin reactions (ie, edema, pallor, erythema), more severe complications can be encountered including methemoglobinemia, central nervous system toxicity, and cardiotoxicity. This article reviewed the literature regarding risk of systemic toxicity associated with use of EMLA in the pediatric and adult population. All 12 clinical trials evaluating the safety of EMLA in either the pediatric or adult population generally followed dosing and administration guidelines set by the manufacturer and reported clinically insignificant plasma levels of methemoglobin, lidocaine, prilocaine, and their respective metabolites. To date, nine pediatric cases and three adult cases of systemic toxicity associated with EMLA have been published. Possible factors that contributed to the development of systemic toxicity include excessive amount of EMLA, large application area, prolonged application time, diseased and/or inflamed skin (eg, vascular malformations, molluscum contagiosum, eczema, previously abraded skin), age less than 3 months, prematurity, and concomitant use of a methemoglobin-inducing agent. Recommendations are provided on how to safely use EMLA to minimize the risk of systemic toxicity.

Topical steroid risk analysis: differentiating between physiologic and pathologic adrenal suppression.

BACKGROUND: Topical corticosteroids are a mainstay of therapy for inflammatory skin disorders. Hypothalamic-pituitary-adrenal (HPA) axis suppression is a potential systemic risk of topical steroid use. Our aim was to review available data on the risk of HPA axis suppression associated with long-term topical steroid use and to distinguish between pathologic and physiologic adrenal suppression. METHODS: We performed a PubMed search for literature that evaluated the risk of HPA axis suppression associated with topical steroid use. RESULTS: Fifteen of sixteen clinical trials reviewed did not report any pathologic adrenal suppression. In the single clinical trial that reported pathologic adrenal suppression, the patients used twice the maximum recommended amount of clobetasol propionate continuously for as long as 18 months. Physiologic adrenal suppression was seen as early as 1-2 weeks after treatment with class I-IV topical corticosteroids. In about half of these patients, cortisol levels spontaneously returned to normal within a few weeks, despite continuous therapy. CONCLUSION: Even when adrenal suppression occurs, topical corticosteroids are unlikely to be associated with clinical signs or symptoms of HPA axis suppression and are extremely safe as long as they are used within the current safety guidelines.

Research gaps in psoriasis: opportunities for future studies.

Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.

Methotrexate toxicity induced by ciprofloxacin leading to psoriatic plaque ulceration: a case report.

We present the case of a 90-year-old woman with psoriasis vulgaris who had been treated with methotrexate for many years. The patient presented with psoriatic plaque ulcerations uniquely limited to the active border as well as acute oral ulcerations and severe gastrointestinal upset after undergoing a course of ciprofloxacin for treatment of a bacterial infection.

Psychodermatology: an overview.

Psychodermatology is an interface between dermatology and psychiatry. The different disorders within psychodermatology can be categorized in 2 ways: by the type of psychodermatologic disorder or by the underlying psychiatric disorder. The types of psychodermatologic disorders include psychophysiological, primary psychiatric, secondary psychiatric, and cutaneous sensory disorder. The psychiatric disorders include anxiety, depression, obsessive-compulsive disorder, and psychosis. This manuscript gives an overview of the different psychodermatologic disorders, underlying psychiatric disorders, and how to manage psychodermatology cases.

Emotional stress as a trigger for inflammatory skin disorders.

Dermatologic disorders comprise 15% to 20% of complaints seen in general practice. Skin disorders result in a negative impact to the patient not only physically but also psychologically, socially, and occupationally. The most common trigger for several inflammatory skin disorders, including psoriasis, is emotional stress. Understanding the significance of emotional triggers to common inflammatory dermatologic disorders is critical to the optimal management of these conditions. This article will provide an overview of the effects of emotional stress on skin disorders and psychotherapeutic options.

Psychopharmacological therapies in dermatology.

When patients with psychodermatologic disorders present in clinic, the dermatologist can refer them to psychiatrists or other mental health care professionals. However, it is often the case that these patients will refuse a psychiatric referral because they either do not believe they have a disorder of psychiatric nature or they feel there is societal stigma associated with psychiatric illness. Therefore, it is essential for dermatologists to understand the common classifications for psychodermatological cases and to know how to optimally treat these patients with pharmacotherapy. The intent of this article is to help guide physicians in understanding the classifications of psychodermatological cases and in managing these conditions with pharmacotherapies. In this article, two classifications for psychodermatological cases are presented, followed by a discussion of medical therapies used to treat the main categories of psychopathologies that are more frequently encountered in dermatology. These include depression, anxiety, delusions, and obsessive-compulsive disorder.