Canadian Expert Consensus on the Use of Halobetasol Propionate/Tazarotene Lotion for Plaque Psoriasis.

INTRODUCTION: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. METHOD: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. RESULTS: The expert panel reached consensus on 20 statements. CONCLUSION: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.

Maintenance of Investigator's Static Global Assessment Response with Once-Daily Crisaborole in Participants with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control. In the CrisADe CONTROL phase III study (ClinicalTrials.gov: NCT04040192), participants aged ≥ 3 months with mild to moderate AD treated with once-daily (QD) crisaborole, following initial treatment success with crisaborole twice daily (BID), had longer periods of flare-free maintenance, a higher number of flare-free days, and a lower number of flares compared with those who received vehicle. The study was an exploratory analysis of data on the maintenance of response per Investigator's Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear]) during the CrisADe CONTROL study through week 52. METHODS: Exploratory endpoints were the time to ISGA response during the open-label run-in period, and the maintenance of ISGA response and the severity and duration of flares during the double-blind maintenance period. Outcomes were stratified by age (participants aged 3 months to < 12 years and ≥ 12 years) and duration of crisaborole BID treatment (< 4 weeks or ≥ 4 weeks) during the open-label run-in period. RESULTS: During the open-label run-in period, the median time to ISGA response was 41.5 days. From week 4 to week 52 of the double-blind maintenance period, the proportion of participants who maintained ISGA response was greater with crisaborole versus vehicle, and this difference was statistically significant up to week 36 (P < 0.05). Duration of flare periods during the maintenance period were 54.1 and 54.0 days for the vehicle and crisaborole-treated groups, respectively. Numerically fewer crisaborole-treated participants experienced a flare with an ISGA score of ≥ 2 compared with vehicle-treated participants (64.8% vs. 74.4%, respectively). Findings were comparable across most subgroups. CONCLUSIONS: Adult and pediatric participants with mild to moderate AD at baseline who had achieved responder criteria (treatment success) with crisaborole BID during the run-in period maintained response per ISGA with crisaborole QD during the double-blind maintenance period through week 52. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04040192.

Atopic dermatitis is a skin disease that causes itchy, red, and dry patches of skin that can affect a person for a long time. Current treatments for atopic dermatitis often fail to keep the symptoms under control. Some creams and ointments applied to the skin (known as topical treatments) can ease the discomfort of atopic dermatitis. Crisaborole is a steroid-free ointment that has been shown to improve symptoms of atopic dermatitis in clinical studies. In a study called the CrisADe CONTROL trial, crisaborole was tested to see if it can keep atopic dermatitis symptoms under control. People who participated in the study were aged 3 months and older and they had mild-to-moderate atopic dermatitis. Participants were asked to use crisaborole on their itchy, red, and dry skin twice daily for 8 weeks. Patients were called "responders" if their symptoms became nearly clear or completely clear based on a doctor's assessment called the Investigator's Static Global Assessment, which rates atopic dermatitis between clear to severe. Some responders were asked to use crisaborole once daily for 52 weeks and another group of responders was asked to use a control (an ointment with no medicine) once daily for 52 weeks. Investigators looked at how long the skin remained nearly clear or completely clear during the 52 weeks. Results of this study showed that after initial treatment success with crisaborole twice daily, adult and pediatric participants who had mild-to-moderate atopic dermatitis were able to keep their skin nearly clear or completely clear with crisaborole once daily.

Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial.

BACKGROUND: Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. OBJECTIVE: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. METHODS: DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. RESULTS: Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P = .0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. LIMITATIONS: Lack of active-comparator. CONCLUSIONS: Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.

Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Prevention of Shingles in Dermatology Patients on Systemic Medications.

The lifetime risk for herpes zoster (HZ) of approximately 1 in 3 is increased with advancing age, a family history of HZ, diseases with altered immune function, immunosuppression, physical trauma and psychological stress. In dermatology, monotherapy with current biologics does not increase risk, however systemic steroids, Janus kinase inhibitors and combination biologic/conventional disease-modifying antirheumatics do. The recombinant zoster vaccine (RZV, Shingrix®), an adjuvanted non-live subunit vaccine against the glycoprotein E subunit of varicella zoster virus, is approved for prevention of HZ in adults ≥50 years of age, and adults ≥18 years of age who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression due to disease or treatment. It is administered as two 0.5 ml intramuscular injections 2-6 months apart. In immunocompromised individuals, the spacing between injections may be reduced to 1-2 months. Where possible, the first dose should be administered at least 14 days before onset of immunosuppressive treatment. Studies in immunocompetent individuals have shown high efficacy including prevention of HZ, postherpetic neuralgia and other complications, with persistence of effect 10 years after vaccination. The acceptable safety profile and efficacy in five different immunocompromised populations support its use in at-risk adult dermatologic patients.

The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity.

Alopecia areata (AA) is a common inflammatory autoimmune disease of the hair which can have a significant negative impact on quality of life (QoL), mental health and productivity. The aim of this scoping review is to elucidate the burden of AA focusing on these three realms. Inclusion criteria included all original manuscripts with no restriction on study type or statistical method written in English (or having an English abstract). For QoL 40 articles were included, 85 for psychiatric comorbidities, and 9 for work/school absenteeism/presenteeism mostly consisting of cross-sectional and observational cohort studies. QoL impairment was detected in over 75% of patients and up to one-third reported extremely severe QoL impairments. Specific QoL dimensions with the greatest impact were embarrassment, social functioning, as well as shopping and/or housework. Cross-sectional studies assessing the psychological burden of adult patients with AA found that the presence of signs of anxiety and/or depression ranged from 30% to 68% and affected all age groups. Rates of work absenteeism and unemployment were significantly higher in AA patients compared to healthy controls. Up to 62% reported making major life decisions including relationships, education and career based on their AA. Additionally, the extensive camouflage techniques and time lost from work led to a strong financial burden for patients and the numerous physician visits added to the healthcare costs. The overall impact of AA stretches much further than simply being an aesthetic concern and can negatively impact every part of an individual's life. An individualized approach and effective treatments will help reduce the psychosocial consequences and distress and return patients to their normal state of health.

Simultaneous Nail and Skin Clearance in Ixekizumab Head-to-Head Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis.

INTRODUCTION: The lifetime incidence of nail psoriasis in patients with psoriasis is 80-90%, with 23-27% of patients having nail psoriasis at any given time. Nail psoriasis is even more prevalent in patients with comorbid psoriatic arthritis. Complete psoriasis clearance, an achievable therapeutic goal, should ideally include the resolution of nail psoriasis. Here, we assessed simultaneous skin and nail clearance in patients with psoriasis across five head-to-head trials comparing ixekizumab with other biologics. METHODS: Data were assessed in patients with moderate-to-severe psoriasis (with or without psoriatic arthritis) with nail psoriasis at baseline from the IXORA-R, IXORA-S, UNCOVER-2, UNCOVER-3, and SPIRIT-H2H trials. Ixekizumab patients received IXEQ2W to week 12 and IXEQ4W beyond week 12. PASI 100 depicted complete skin clearance, and PGA-F 0 (IXORA-R) or NAPSI 0 (all other trials) depicted complete nail clearance. Treatment comparisons were evaluated using the Cochran-Mantel-Haenszel test. Non-responder imputation was used for missing data. RESULTS: Ixekizumab achieved significantly greater simultaneous skin and nail complete clearance than etanercept (UNCOVER-2: p < 0.001 and UNCOVER-3: p < 0.001) at week 12, demonstrating an efficacious and rapid response. Across all five head-to-head trials, ixekizumab achieved a high rate of simultaneous skin and nail clearance (range: 28.6-45.9% of patients) by week 24 that was maintained up to week 52 (range: 40.5-51.4% of patients). Ixekizumab achieved numerically greater simultaneous complete clearance than guselkumab at week 24 (p = 0.079), but statistically significant greater simultaneous clearance compared to ustekinumab (p < 0.001) and adalimumab (p = 0.006) at week 24 and week 52 (p < 0.001 and p = 0.007, respectively). CONCLUSION: In five head-to-head trials, ixekizumab-treated patients had higher rates of simultaneous complete skin and nail clearance compared to etanercept, guselkumab, ustekinumab, and adalimumab, thereby reinforcing ixekizumab's ability to achieve high levels of efficacy in multiple domains of psoriatic disease. TRIAL REGISTRATION: NCT01474512, NCT01597245, NCT01646177, NCT03573323, NCT02561806, and NCT03151551.

Efficacy of guselkumab versus secukinumab in subpopulations of patients with moderate-to-severe plaque psoriasis: results from the ECLIPSE study.

PURPOSE: Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age (<45, 45 to <65, and ≥65 years old), body weight, body mass index (BMI), psoriasis disease severity (body surface area, disease duration, PASI, and IGA), psoriasis by body regions (head, trunk, upper and lower extremities), and prior psoriasis medication history at week 48. RESULTS: Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. CONCLUSIONS: Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

Efficacy and safety of proactive treatment with twice-weekly topical Cal/BD foam in patients with plaque psoriasis undergoing HPA-axis testing: a PSO-LONG subgroup analysis.

OBJECTIVE: In PSO-LONG, long-term proactive management (PAM) of psoriasis with fixed-dose combination calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) aerosol foam was superior to conventional reactive management. This post-hoc analysis investigated long-term PAM with Cal/BD foam in PSO-LONG patients who could be more susceptible to corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression. METHODS: Efficacy and safety of PAM with Cal/BD foam (twice-weekly) versus reactive management (twice-weekly vehicle foam), with once-daily rescue Cal/BD foam for four weeks following relapse, was assessed in the HPA subgroup (n = 66); patients had moderate-to-severe psoriasis (physician global assessment score ≥3; 10-30% body surface area affected). Primary endpoint was time to first relapse. RESULTS: PAM with Cal/BD foam was associated with longer median time to first relapse (111 versus 31 days), reduced risk of first relapse (hazard ratio: 0.49; p = .029), greater proportion of days in remission (17%; p = .001) and reduced rate of relapse (60% reduction; p < .001) than reactive management. Adverse events occurred in 37.5% (PAM) and 47.1% (reactive management) of patients, with no new safety signals. No clinically significant HPA-axis suppression was observed. CONCLUSION: Efficacy of PAM with Cal/BD foam is maintained in patients with moderate-to-severe psoriasis, with no new safety signals.

Skin care and hygiene among healthcare professionals during and after the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 pandemic has necessitated enhanced protection against viral transmission among healthcare professionals, particularly relating to handwashing and personal protective equipment. Some of these requirements may persist for years to come. They bring associated concerns around skin hygiene and general care, with damage to the face and hands now a well-documented consequence among healthcare professionals. This review assesses optimal skin care during the severe acute respiratory syndrome coronavirus 2 pandemic and in the "new normal" that will follow, identifies current knowledge gaps, and provides practical advice for the clinical setting. Regular, systematic hand cleaning with soap and water or an alcohol-based hand rub (containing 60%-90% ethanol or isopropyl alcohol) remains essential, although the optimal quantity and duration is unclear. Gloves are a useful additional barrier; further studies are needed on preferred materials. Moisturization is typically helpful and has proven benefits in mitigating damage from frequent handwashing. It may be best practiced using an alcohol-based hand rub with added moisturizer and could be particularly important among individuals with pre-existing hand dermatoses, such as psoriasis and eczema. Face moisturization immediately prior to donning a mask, and the use of dressings under the mask to reduce friction, can be helpful dermatologically, but more work is required to prove that these actions do not affect seal integrity. Nonetheless, such measures could play a role in institutional plans for mitigating the dermatologic impact of transmission control measures as we exit the pandemic.

Fixed Combination Halobetasol Propionate and Tazarotene Lotion for Plaque Psoriasis.

A novel fixed combination lotion containing the super-potent corticosteroid halobetasol propionate 0.01% and retinoid tazarotene 0.045% (Duobrii™) has recently been introduced and indicated for the treatment of moderate to severe plaque psoriasis in adults. Studies have shown that there is synergy between the ingredients and that the product can be safely used intermittently for up to 1 year. Treatment success (i.e., Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] and at least a 2-grade improvement from baseline) occurred in 58.8% of participants at some point in a 1-year clinical trial. Persistence of treatment success is common after treatment discontinuation. Most treatment-emergent adverse events are application site reactions, mild to moderate in intensity, and occur primarily during the first 12 weeks. Counselling should be considered to optimize treatment outcomes.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

Emerging paradigm shift toward proactive topical treatment of psoriasis: A narrative review.

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D3 analogs. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift toward proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety.

Pregnancy Outcomes in Women With Moderate-to-Severe Psoriasis From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Importance: Prospective data are limited on pregnancy outcomes among women with psoriasis who may be receiving biologic or conventional systemic therapy. Objective: To report pregnancy outcomes observed in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Design, Setting, and Participants: This cohort study used data from PSOLAR, a multicenter, disease-based, observational registry evaluating long-term safety and clinical outcomes for patients receiving or eligible to receive treatment for psoriasis with biologics and/or conventional systemic therapies. Of 12 090 enrollees, 5456 were women (45.1%), and 2224 women were of childbearing age (18-45 years). Participants had a total of 12 929 patient-years of follow-up (median, 7.2 [range, 3.3-8.0] years per patient). Data were collected from June 20, 2007, to August 23, 2019, and analyzed from April 23 to June 23, 2020. Exposures: Exposure to biologics within the prenatal period (≤1 year before birth or ≤6 months before spontaneous abortion) or at any other time. Main Outcomes and Measures: Descriptive summaries of pregnancies and pregnancy-related outcomes were self-reported in PSOLAR, including births, stillbirths, spontaneous abortions, and elective terminations. Live birth characteristics collected in PSOLAR include whether a birth was full-term (≥37 weeks) or premature (<37 weeks) and whether neonatal adverse events or congenital anomalies occurred. Results: A total of 298 pregnancies occurred among 220 women (mean [SD] age, 27.8 [5.2] years), and the general fertility rate was 18.9 per 1000 women aged 18 to 45 years. Of the 298 pregnancies, 244 (81.9%) resulted in birth, 41 (13.8%) ended in spontaneous abortion, and 13 (4.4%) were electively terminated. Gestational age was available for 243 births; 221 infants (90.9%) were full-term, and 22 (9.1%) were born prematurely. Birth outcomes included 231 healthy newborns, 10 infants with a neonatal problem, 2 infants with a congenital anomaly, and 1 stillbirth. Of the 298 pregnancies, 252 were associated with biologic exposure before or during pregnancy. Pregnancy outcomes for women exposed to biologics were similar to those for women exposed to nonbiologics. Among women who became pregnant, mean (SD) age at the time of pregnancy outcome was 30.9 (4.8) years; at enrollment into the registry, 74 of 219 (33.8%) had obesity, and 121 of 220 (55.0%) were past or current smokers. Conclusions and Relevance: The findings of this cohort study suggest that pregnancy outcomes in PSOLAR have remained consistent with previous reports. Overall and live birth outcomes were similar to those for the general population.

Leveraging Blockchain Technology for Informed Consent Process and Patient Engagement in a Clinical Trial Pilot.

Objective: Despite the implementation of quality assurance procedures, current clinical trial management processes are time-consuming, costly, and often susceptible to error. This can result in limited trust, transparency, and process inefficiencies, without true patient empowerment. The objective of this study was to determine whether blockchain technology could enforce trust, transparency, and patient empowerment in the clinical trial data management process, while reducing trial cost. Design: In this proof of concept pilot, we deployed a Hyperledger Fabric-based blockchain system in an active clinical trial setting to assess the impact of blockchain technology on mean monitoring visit time and cost, non-compliances, and user experience. Using a parallel study design, we compared differences between blockchain technology and standard methodology. Results: A total of 12 trial participants, seven study coordinators and three clinical research associates across five sites participated in the pilot. Blockchain technology significantly reduces total mean monitoring visit time and cost versus standard trial management (475 to 7 min; P = 0.001; €722 to €10; P = 0.001 per participant/visit, respectively), while enhancing patient trust, transparency, and empowerment in 91, 82 and 63% of the patients, respectively. No difference in non-compliances as a marker of trial quality was detected. Conclusion: Blockchain technology holds promise to improve patient-centricity and to reduce trial cost compared to conventional clinical trial management. The ability of this technology to improve trial quality warrants further investigation.

Multidisciplinary Real-World Experience With Bilastine, a Second Generation Antihistamine

Introduction: Allergic conditions frequently require treatment with antihistamines. First-generation antihistamines can potentially interfere with restful sleep, cause "morning after" effects, impair learning and memory, and reduce work efficiency. Second-generation antihistamines, such as bilastine, have been demonstrated to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events. Method: A real-world case project was developed to help optimize patient care by recognizing the role bilastine can play for allergic conditions where antihistamine treatment is needed. The presented real-world patient cases conducted by the panel members are supported with evidence from the literature, where available. Any discussion concerning off-label use should be considered an expert opinion only. Results: The real-world cases presented here used bilastine in conditions such as perennial and seasonal allergic rhinitis, chronic urticaria, as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions. The treated patients were between 9 and 76-years old providing information on a full spectrum of patients that require treatment with antihistamines. Conclusions: The presented real-world cases using the second-generation antihistamine, bilastine, demonstrated favorable outcomes for the treated patients. While effectively relieving symptoms, the antihistamine was reported to be safe and well-tolerated. J Drugs Dermatol. 2020;19(2)145-154. doi:10.36849/JDD.2020.4835

Efficacy and Safety of Ixekizumab Through 5 Years in Moderate-to-Severe Psoriasis: Long-Term Results from the UNCOVER-1 and UNCOVER-2 Phase-3 Randomized Controlled Trials.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years. METHODS: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported. RESULTS: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted. CONCLUSIONS: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.

Comparison of topical antiaging creams in the management of lateral canthal lines.

OBJECTIVE: This study compared an antiaging treatment with two currently marketed cosmetic antiaging products for the treatment of lateral canthal lines ("crow's feet"). METHODS: Healthy female volunteers (72) aged of 54.6 years (mean) having fine-to-moderate wrinkles in the lateral canthal areas were randomized to one of three treatments applied daily over 28 days: Group A (Purgenesis™ Day Cream, Purgenesis™ Eye Cream, and Purgenesis™ Night Cream); Group B (Prevage® Eye Lotion, Prevage® Day Cream, and Prevage® Night Cream); or Group C (La Mer® Eye Balm, Crème de La Mer® , and La Mer® Night Cream). The effects on anti-wrinkle properties and for sensory attributes and general performance were evaluated on Days 1, 7, and 28. RESULTS: Skin hydration improved significantly at all time points in Groups A and B, and at Day 28 in Group C. Group A patients experienced significant improvements in measured skin elasticity parameters at Day 28; extensibility and maximum amplitude were significantly better at Day 28 in Groups B and C. Benefits were also seen in profilometric parameters with statistical significance only in Group A Volunteer tolerance was good with all three treatments, although moderate and high levels of adverse events were numerically higher in Group B than in Groups A or C, and levels of slight discomfort were significantly more prevalent in Group B. CONCLUSION: The Purgenesis™ antiaging treatment significantly improved skin hydration, elasticity, and profilometry parameters during a 28-day study. This therapy was found to be well tolerated and effective in countering the cutaneous signs of aging.

Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial.

Ixekizumab was efficacious in treating moderate-to-severe genital psoriasis over 12 weeks. We evaluated the long-term efficacy and safety of ixekizumab for up to 52 weeks. Patients were randomized to 80 mg ixekizumab every 2 weeks or to placebo through Week 12, then received 80 mg open-label ixekizumab every 4 weeks through Week 52. In patients initially randomized to ixekizumab, clear or almost clear genital skin was achieved for 73% of patients at Week 12 and 75% at Week 52. Persistent improvements were also observed for overall psoriasis, genital itch, and the impact of genital psoriasis on the frequency of sexual activity. The safety profile was consistent with studies of ixekizumab in patients with moderate-to-severe plaque psoriasis. Ixekizumab provided rapid and persistent improvements in the signs and symptoms of genital psoriasis for up to 52 weeks of treatment.

Off-Label Use of Topical Calcineurin Inhibitors in Dermatologic Disorders.

Off-label prescribing is a common practice in dermatology, particularly when uncommon dermatologic diseases have limited or no approved treatment options. Topical calcineurin inhibitors are approved for the treatment of eczema, and their anti-inflammatory, immunomodulatory, and steroid-sparing effects make them an attractive therapeutic option for a wide variety of other dermatologic diseases. This review summarizes and qualifies the available evidence supporting the clinical effectiveness of tacrolimus ointment and pimecrolimus cream in non-eczema indications. There is high-quality evidence supporting the effectiveness of topical calcineurin inhibitors in multiple dermatological disorders including vitiligo; psoriasis of the face, folds, and genitals; seborrheic dermatitis; chronic hand dermatitis; contact dermatitis; oral lichen planus; lichen sclerosus; morphea; and cutaneous lupus erythematosus. Lower-quality evidence suggests they may be considered as an option in many other cutaneous disorders.