Neurogenic Rosacea Treatment: A Literature Review.

Rosacea is a chronic skin disorder involving central facial erythema secondary to vascular instability and cutaneous inflammation. Rosacea is divided into different subtypes based on the morphology of the rash — erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea. A less-known subtype called neurogenic rosacea has been proposed to categorize patients suffering from rosacea with erythematous flushing and burning sensation that is refractory to traditional treatment. There is minimal data on this subgroup of rosacea patients and its potential treatment options. This review aims to explore current medical literature to define characteristics of neurogenic rosacea and its management. We performed a systematic search of PubMed database and identified 6 articles meeting inclusion criteria with a total of 37 patients with suspected neurogenic rosacea. Combination treatments with topicals (eg, metronidazole, brimonidine), as well as oral medications including vascular (eg, beta blockers), psychiatric (eg, diazepam, duloxetine), neurologic (eg, pregabalin, sumatriptan), and antibiotic agents (eg, rifaximin), were often cited to have better outcomes, but this finding was highly variable between patients. There were isolated reports of effective management with onabotulinumtoxinA intradermal injections and endoscopic thoracic sympathectomy treatment. Current literature supports selecting agents aimed at treating the major symptom pattern (eg, erythema, telangiectasias, burning sensation). Neurogenic rosacea treatment: a literature review. Ivanic MG, Oulee A, Norden A, et al. J Drugs Dermatol. 2023;22(6):566-571. doi:10.36849/JDD.7181  .

Phototherapy and DNA Damage: A Systematic Review.

Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.

Real-world dose escalation of biologics for moderate-to-severe psoriasis in the United States.

AIM: To compare real-world dose escalation of risankizumab with other US Food and Drug Administration (FDA)-approved biologic treatments for management of moderate-to-severe psoriasis (PsO) in the United States. METHODS: The Merative® MarketScan® Research Database was used to identify adults with ≥2 medical claims for PsO, ≥3 claims of the index biologic medication in the maintenance period, and ≥6 months continuous enrollment pre-induction and ≥6 months after initiation of the maintenance period. Dose escalation was defined as ≥2 dosing intervals where the average daily dose was ≥30% higher than the expected daily dose (per FDA-approved dosing). Comparisons between risankizumab and other cohorts were made using chi-square tests and logistic regression models. RESULTS: At the 30% threshold, the percentage of patients with dose escalation in the full maintenance period was significantly lower with risankizumab (2.0%) compared with other drug classes (tumor necrosis factor, interleukin (IL)-12/23, IL-17, or other IL-23 inhibitors: 17.6%, 10.0%, 18.3%, or 7.1%, respectively; p < 0.0001 for each) and individual biologics (adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; 17.9%, 10.0%, 15.7%, 18.0%, and 7.2%, respectively; p < 0.0001). CONCLUSION: A significantly lower proportion of risankizumab-treated patients with PsO had dose escalations compared with patients treated with other biologics.

Treatment patterns and healthcare costs among patients with psoriasis initiating apremilast or biologics: a retrospective claims database cohort analysis.

OBJECTIVE: This study aimed to compare treatment patterns and healthcare costs for patients with psoriasis who initiate apremilast, tumor necrosis factor inhibitor, or interleukin inhibitor. METHODS: This retrospective cohort study used Optum Clinformatics® Data Mart to identify propensity score-matched patients initiating apremilast, tumor necrosis factor inhibitors, or interleukin inhibitors, with 12-month baseline and 24-month follow-up data. Switch, discontinuation, persistence, healthcare resource utilization, and total healthcare costs were assessed. RESULTS: Twenty-four-month switch rates were highest for tumor necrosis factor inhibitors (32%), followed by apremilast (21%) then interleukin inhibitors (14%). Mean (SD) per-patient-per-month costs for switchers were lowest for apremilast ($4213 [$2304]), higher for tumor necrosis factor inhibitors ($5274 [$2280]), and highest for interleukin inhibitors ($5539 [$2296]; p < .001), primarily attributable to pharmacy costs: $3466 (apremilast), $4432 (tumor necrosis factor inhibitor), and $4721 (interleukin inhibitor). LIMITATIONS: Psoriasis severity is absent from claims data; cost outcomes may be influenced by more severe psoriasis being more costly. CONCLUSION: Switching psoriasis treatment is common and increases over time. Apremilast initiators had lower switch rates and costs compared with tumor necrosis factor inhibitors, despite lower effectiveness reported in previous studies, perhaps indicating patient preference for oral treatment. Additional oral options may be desirable for this population.

Risk of Skin Cancer with Phototherapy in Moderate-to-Severe Psoriasis: An Updated Systematic Review.

Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to conduct a systematic review of skin cancer risk for psoriasis patients treated with phototherapy. To achieve our goal, we searched Cochrane, PubMed, and Embase databases. We aimed to evaluate existing literature (from July 1, 2010, to December 31, 2020) on phototherapy for all Fitzpatrick skin phototypes (FSP) which includes 71 articles, and eight articles being categorized in this review. Five studies did not report an increased skin cancer risk with narrowband-ultraviolet blue (UVB) and unspecified UVB for FSP II through VI, with one study not reporting FSP. Three studies did report an increased risk of skin cancer with narrowband-UVB and broadband-UVB for FSP I-VI, with one study also not specifying skin phototypes or UVB phototherapy type. Additionally, a study with psoralen and ultraviolet A with and without narrowband-UVB demonstrated an increased risk of skin cancer in phototypes III and IV. The most commonly reported secondary outcomes with phototherapy were actinic keratosis (123) and solar lentigines (10). Numerous patients were also on additional therapies including methotrexate, acitretin, and biologics. Study limitations include publication bias due to limited number of studies published on this topic in the last ten years along with heterogeneity in reporting. The relationship between phototherapy, psoriasis, and cutaneous oncogenic risk remains contradictory. While phototherapy for psoriasis is an efficacious therapy, further studies are needed to understand the cutaneous oncogenic risk based on FSP to help clinicals tailor treatment recommendations based on skin phototypes.

Interleukin-17 Inhibitor Combination Therapies for the Treatment of Psoriasis: A Systematic Review.

Objective: Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis. Methods of Literature Search: By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality. Results: Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases. Limitations: Our results are limited by the lack of data from RCTs. Conclusion: Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.

Review of Apremilast Combination Therapies in the Treatment of Moderate to Severe Psoriasis.

Psoriasis is a chronic inflammatory skin condition resulting from the dysregulation of cytokines. Apremilast, an oral phosphodiesterase-4 inhibitor is approved by the Federal Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in patients who are eligible for phototherapy or systemic therapy. The drug increases cyclic adenosine monophosphate, cAMP, modulating the expression of pro-inflammatory cytokines. This review aims to explore and categorize current literature describing the efficacy and safety profile of the addition of apremilast to existing therapies including topicals, phototherapy, and systemic agents for the treatment of psoriasis. One database was used for the literature search. Seventeen studies with 617 patients met inclusion criteria and were included. Fifteen studies demonstrated beneficial results with excellent safety and efficacy of apremilast combination therapy (CT). Apremilast has been shown to improve the quality of life and reduce symptom severity in moderate to severe psoriasis. The drug’s simple dosing schedule with mild side effect profile makes it a practical option for patients as combination therapy. J Drugs Dermatol. 2021;20(8):837-843. doi:10.36849/JDD.5845.

Comparison of guidelines for the use of Ustekinumab for psoriasis in the United States, Europe, and the United Kingdom: A critical appraisal and comprehensive review.

The aim of this review is to compare and contrast evidence-based clinical practice guidelines from global dermatological organizations for the use of ustekinumab in psoriasis. Clinical practice guidelines from the American Academy of Dermatology, National Psoriasis Foundation, British Association of Dermatologists, and European S3 were reviewed and compared. Practice guidelines from the three dermatological organizations are similar with regards to treatment dosage and initiation but differ in their recommendations for baseline screening and interval laboratory monitoring, treatment in patients undergoing surgery or receiving live vaccines, and treatment contraindications. Ustekinumab is an effective and well-tolerated systemic treatment for patients with psoriasis and should be considered in the line of therapy that dermatologists discuss with their patients. Consideration should be given to evidence-based practice guidelines of global dermatology organizations to effectively guide treatment decisions in patients with psoriasis.

Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis with Comorbid Conditions and Special Populations: A Review.

The emergence of data from clinical trials of biologics, the approval of new biologics, and our improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for the treatment of moderate-to-severe psoriasis. Biologics currently approved for the treatment of psoriasis include tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors, ustekinumab (an IL-12/23 inhibitor), and IL-23 inhibitors. Data from clinical trials and studies of the safety and efficacy of biologics provide essential information for the personalization of patient care. We discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment recommendations according to current evidence, and propose psoriasis treatment algorithms. Our discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer, lymphoma, and latent tuberculosis. We make evidence-based treatment recommendations for special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and pregnant and breastfeeding patients with psoriasis. Ultimately, individualized recommendations that consider patient preferences, disease severity, comorbid conditions, and additional risk factors should be offered to patients and updated as new trial data emerges.

Two-Year US Pharmacovigilance Report on Brodalumab.

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. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. METHODS: This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. RESULTS: Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn's disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. CONCLUSIONS: This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.

A systematic review of treatment strategies for erythrodermic psoriasis.

Background: Erythrodermic psoriasis (EP) is a severe, rare form of psoriasis that can be life threatening. Treatment of EP is usually based on anecdotal evidence or past clinical experience, which is in part due to the rarity and often emergent nature of this psoriasis subtype.Methods: In December 2018, a keyword search for 'erythrodermic psoriasis' and 'treatment' was conducted. All studies investigating treatment strategies for EP in at least 2 patients were included in this review.Results: The database search yielded 921 results, and 23 studies comprising over 200 patients with EP were included in the final analysis. Biologics including tumor necrosis factor inhibitors (infliximab [n = 4], etanercept [n = 2], and adalimumab [n = 1]), interleukin-17 inhibitors (secukinumab [n = 3], ixekizumab [n = 2], and brodalumab [n = 1]), ustekinumab (n = 4), and guselkumab (n = 1) have been shown to rapidly achieve clinical improvement in patients with EP. The included studies also demonstrated efficacy of systemic agents cyclosporine (n = 4), etretinate (n = 3), and methotrexate (n = 1).Conclusions: A fair number of poor-quality studies support the use of various biologic and systemic therapies in the treatment of EP. Treatment of EP should be based on the severity of the clinical scenario as well as patient comorbidities.

Topical Scar Treatment Products for Wounds: A Systematic Review.

BACKGROUND: There is an increasing number of over-the-counter topical products that are said to prevent pathologic scar formation and improve scar cosmesis. However, robust clinical data are lacking to substantiate these claims and to guide selection of topical products. OBJECTIVE: To determine the effectiveness of topical scar management products, including silicone gel, Allium cepa onion extract, vitamin E, trolamine, and microporous tape. METHODS AND MATERIALS: A PubMed search (2005-2019) was performed to identify studies of topical scar management products. Randomized controlled trials (RCTs), quasi-RCTs, meta-analyses, and controlled clinical trials were included for analysis. RESULTS: A total of 34 trials were included in this study. Of the 16 trials investigating silicone gel sheets, numerous high-quality RCTs found that silicone gel sheets and silicone gels significantly improved scar outcomes. Only a limited number of studies supported the effectiveness of onion extract, vitamin E, trolamine, and microporous tape products. CONCLUSION: Silicone gel products are an effective noninvasive treatment to prevent formation of pathologic scars and improve mature scars. Further high-quality studies are needed to elucidate the long-term effectiveness of these therapies.