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.

The Acne Education Project: An educational initiative to improve acne health literacy and promote help-seeking behavior in young adolescents.

BACKGROUND: Acne vulgaris is an inflammatory skin condition that is associated with poor acne health literacy. Diminished acne health literacy leads to delays in the access of health care, resulting in mismanagement, disfigurement, and psychosocial morbidity. This study evaluates the potential role of early acne education in young adolescent populations to improve acne health literacy and facilitate help-seeking behavior. METHODS: The Acne Education Project is a Canadian medical student-led initiative founded to create evidence-based resources to increase acne health literacy. A 45-min interactive Zoom presentation on acne was created and delivered to 2292 students ages 9-13 in British Columbia, Canada. A quality improvement survey was administered pre-intervention, immediate post-intervention, and 1-month post-intervention to evaluate baseline acne knowledge and knowledge retention to guide presentation and resource development. RESULTS: Responses from 676 unique individuals were collected. Analysis using linear mixed-effects models demonstrated that respondents were significantly more confident in their general knowledge of acne, strategies to prevent acne, identification of psychosocial sequelae of acne, and more willing to seek help immediately post-intervention (p < .001). Differences in scores were not fully preserved in magnitude at the 1-month post-intervention assessment. However, students still scored significantly higher in all categories compared to the pre-intervention baseline (p < .001). CONCLUSION: Our findings suggest that early acne education can improve acne health literacy and promote help-seeking behavior. Given the potential long-term implications, further research is needed to explore the long-term impact of early acne education and the benefit of integrating acne education into the public education curriculum in Canada.

INDIVIDUAL ARTICLE: NECOM 3: A Practical Algorithm for the Management of Radiation Therapy-Related Acute Radiation Dermatitis.

BACKGROUND: In the Nordic European countries in 2020, cancer diagnoses accounted for 175,925 patients. About 50% of cancer patients receive radiation therapy (RT), which may lead to radiation dermatitis (RD). Notably, patients with breast, head, neck, and anal cancers may be prone to developing RD. However, few algorithms exist for the prevention and treatment of RD. METHODS: The Nordic European Cutaneous Oncodermatology Management (NECOM) project aims to improve cancer patient outcomes by offering tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm for preventing and managing acute RD (ARD) is intended to promote healthy skin and reduce RT-related ARD, improving cancer patient outcomes.  Results: The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and opinion-based practical algorithm for ARD to support all stakeholders in the Nordic European healthcare setting. The algorithm starts with skin-preserving therapy, followed by skin condition assessment and patient-specific interventions based on the grade of RD present.  Conclusion: ARD may lead to symptoms of pruritus and pain, decreased QoL and morbidity, and treatment interruptions. Patient education on the prevention of RD and treatment recommendations given in the NECOM 3 algorithm may help prevent and manage RD and improve the overall care of patients receiving RT. J Drugs Dermatol. 2023;22:11(Suppl 2):s3-s10.

Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. METHODS: In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points. RESULTS: A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). CONCLUSIONS: Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).

The burden of palmoplantar pustulosis: A Canadian population-based study of inpatient care, emergency departments, and outpatient clinics.

Background: Not much is known about the burden of palmoplantar pustulosis (PPP). Objectives: To document the burden of PPP in Canada, and to compare with psoriasis vulgaris (PV). Methods: Adult Canadians (excluding the province of Quebec) hospitalized or visiting an emergency department (ED) or hospital-/community-based clinic between April 1, 2007, and March 31, 2020, with a diagnostic code indicating PPP (ICD-10-CA: L40.3) or PV (ICD10-CA: L40.9 or L40.0) were identified using Canadian administrative data. 10-year prevalent- and 3-year incident-based approaches were conducted. Costs were determined when the most responsible diagnosis (MRD) for the admission was PPP or PV (MRD costs) and for all reasons (all-cause costs). Results: In the prevalence analysis, the 10-year mean (standard deviation [SD]) and MRD costs were $544 ($1874) for PPP and $222 ($1828) for PV (P < .01). In the incidence analysis, PPP patients had higher 3-year mean (SD) MRD costs ($1078 [$2705]) than PV ($503 [$2267]) (P < .01). All-cause costs were lower for the PPP cohort in the prevalent and incident analyses. There were no differences in all-cause inpatient mortality between PPP and PV. Limitations: Physician and prescription data were not available. Conclusion: PPP patients incurred significantly higher MRD costs than PV patients.

Psoriasis and Skin Barrier Dysfunction: The Role of Gentle Cleansers and Moisturizers in Treating Psoriasis.

BACKGROUND: Psoriasis is a chronic immune-mediated dermatologic disorder with multisystemic comorbidities, which is effectively treated with a range of prescription therapies. Studies have reported epidermal barrier abnormalities in the lesional skin of psoriasis patients; however, there is currently insufficient information about skin barrier function in psoriasis patients. This review discusses the potential role of gentle cleansers and moisturizers in the management of psoriasis and in promoting a healthy skin barrier. METHODS: A literature review was followed by the authors' discussions and agreement on 5 statements to provide expert guidance for gentle cleansers and moisturizer use in psoriasis patients. RESULTS: In a workshop, the authors provided feedback on 15 draft statements created prior to the meeting, and agreed upon 5 statements. The authors agreed that guidelines rarely mention skincare for psoriasis patients, demonstrating a potential knowledge gap. Skincare may play a role in managing psoriasis as an adjuvant treatment of acute psoriasis and for maintenance treatment of healing skin during asymptomatic periods. Studies of patients with psoriasis applying topical moisturizers (such as those containing salicylic acid or ceramides) showed softened plaques, enhancing the absorption of topical treatments such as corticosteroids. Studies applying ceramide-containing skincare showed an overall improvement in the appearance of the skin and provided relief for psoriasis. CONCLUSION: The authors agreed that skincare and barrier restoration in treating psoriasis is a relatively new concept for most dermatologists. There is a need to develop a more robust body of evidence on skincare for psoriasis to influence clinical practice in a meaningful way. Kircik L, Alexis AF, Andriessen A, et al. Psoriasis and skin barrier dysfunction: the role of gentle cleansers and moisturizers in treating psoriasis. J Drugs Dermatol. 2023;22(8):773-778. doi:10.36849/JDD.7411.

A plain language summary on ritlecitinib treatment for adults and adolescents with alopecia areata.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in The Lancet. ALLEGRO-2b/3 looked at how well and safely the study medicine, ritlecitinib, works in treating people with alopecia areata ('AA' for short). The immune system protects your body from outside invaders such as bacteria and viruses. AA is an autoimmune disease, meaning a disease in which one's immune system attacks healthy cells of the body by mistake. In AA, the immune system attacks hair follicles, causing hair to fall out. AA causes hair loss ranging from small bald patches to complete hair loss on the scalp, face, and/or body. Ritlecitinib is a medicine taken as a pill every day, by mouth, that is approved for the treatment of severe AA. It blocks processes that are known to play a role in causing hair loss in patients with AA. WHAT WERE THE RESULTS OF THE STUDY?: Adults and adolescents (12 years and older) took part in the ALLEGRO-2b/3 study. They either took ritlecitinib for 48 weeks or took a placebo (a pill with no medicine) for 24 weeks. Participants taking placebo later switched to taking ritlecitinib for 24 weeks. The study showed that participants taking ritlecitinib had more hair regrowth on their scalp after 24 weeks than those taking the placebo. Hair regrowth was also seen on the eyebrows and eyelashes in participants taking ritlecitinib. Hair regrowth continued to improve to week 48 with continued ritlecitinib treatment. In addition, more participants taking ritlecitinib reported that their AA had 'moderately' or 'greatly' improved after 24 weeks than those taking the placebo. Similar numbers of participants taking ritlecitinib or placebo had side effects after 24 weeks. Most side effects were mild or moderate. WHAT DO THE RESULTS OF THE STUDY MEAN?: Ritlecitinib was an effective and well-tolerated treatment over 48 weeks for people with AA. Clinical Trial Registration: NCT03732807 (phase 2b/3 ALLEGRO study).

The burden associated with generalized pustular psoriasis: A Canadian population-based study of inpatient care, emergency departments, and hospital- or community-based outpatient clinics.

Background: Not much is known about the burden of generalized pustular psoriasis (GPP). Objectives: To document the burden of GPP in Canada and to compare it with psoriasis vulgaris (PV). Methods: National data were used to identify Canadian adult patients with GPP or PV hospitalized or visiting an emergency department (ED) or hospital-/community-based clinic between April 1, 2007, and March 31, 2020. Analyses of 10-year prevalence and 3-year incidence were conducted. Costs were determined when the most responsible diagnosis (MRD) was GPP or PV (MRD costs) and for all reasons (all-cause costs). Results: In the prevalence analysis, 10-year mean (SD) MRD costs were $2393 ($11,410) for patients with GPP and $222 ($1828) for those with PV (P < .01). In the incidence analysis, patients with GPP had higher 3-year mean (SD) MRD costs ($3477 [$14,979] vs $503 [$2267] for PV; P < .01). Higher all-cause costs were also associated with patients with GPP. Inpatient/ED mortality was higher in the GPP group in our 10-year prevalence (9.2% for patients with GPP vs 7.3% for those with PV; P = .01) and 3-year incidence (5.2% for patients with GPP and 2.1% for those with PV; P = .03) analyses. Limitations: Physician and prescription drug data were not available. Conclusion: Patients with GPP incurred higher costs and mortality than patients with PV.

Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial.

Importance: Current topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety. Objective: To assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk. Design, Setting, and Participants: This multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020. Interventions: Once-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks. Main Outcomes and Measures: The main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed. Results: A total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P < .001). Roflumilast-treated patients had statistically significantly higher rates of IGA success vs vehicle at week 2, the first time point assessed. Mean (SD) reductions (improvements) on the WI-NRS at week 8 were 59.3% (52.5%) vs 36.6% (42.2%) in the roflumilast and vehicle groups, respectively (P < .001). Roflumilast was well tolerated, with the rate of adverse events similar to that of the vehicle foam. Conclusions and Relevance: The results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04091646.

Measuring h-index and scholarly productivity in academic dermatology in Canada.

Promotion in academia heavily relies on research productivity. The h-index is a standardized metric used to quantify research productivity at the individual level. We evaluated factors associated with h -index in dermatology across select Canadian academic centers with special focus on sex and academic rank. Medical academic centers throughout Canada with dermatology training programs were included. For each faculty member, we extracted the following data from public sources: sex, graduate degree, academic rank, years since the Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) certification or equivalent, recent Canadian Institutes of Health Research (CIHR) funding and H-index (based on Scopus author profile). Log-linear univariate and multivariate regression analyses were performed to evaluate the association between h-index and these factors. An ordinal logistic regression was performed to explore sex differences in academic ranking. Our results showed that out of 300 faculty members across Canada, 155 were females (51.67%) and 145 were male (48.33%). H-index was available for 279 dermatologists. The average h-index was 8.35 (SD 11.53) and the median was 4.00 (1st quartile = 2.00, 3rd quartile = 10.00). Higher h-index was associated with more years since dermatology certification, successive academic rank, graduate degree and recent CIHR funding, but not with sex. In conclusion, h-index was not associated with sex when controlling for potential confounders. These results could reflect recent demographic changes in the field with an increase in newly appointed female dermatologists. Longitudinal assessment of academic productivity in dermatology is needed to assess the impact of continued efforts to promote equal opportunities in the field.

Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel.

BACKGROUND: Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. OBJECTIVES: We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?" METHODS: We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. RESULTS: We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. CONCLUSIONS: Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.

Patients with previously treated cancer have a higher chance of cancer recurrence compared with the general population. With cancer incidence rising worldwide, doctors across medical specialities will need to treat other medical conditions, including inflammatory diseases such as psoriasis, in these patients. Effective systemic therapies for psoriasis reduce immune cell activity. Accordingly, there are concerns that treatments for psoriasis could worsen cancer recurrence/progression and infectious complications. There is not enough quality evidence to make broad recommendations for treating other inflammatory conditions in patients with a history of cancer. To guide patient and doctor discussions, we asked: what are effective and safe treatments when patients with treated solid tumours need systemic therapy (pills or injections) for their psoriasis? We focused on patients with solid tumours and excluded blood and skin cancers. Our panel of experts, including 12 dermatologists and 3 medical oncologists, reviewed direct and indirect evidence to answer this question. Considering the totality of evidence reviewed, the expert panel drafted and rated their level of support for opinion statements on important considerations in treating patients with psoriasis who have a history of solid tumours. By making inferences on systemic psoriasis therapies in this heterogeneous population, we take the onus off individual physicians to review the indirect data. This process may help answer questions in other disease populations where direct evidence is scarce or absent. To support treatment decisions, doctors should have a guided conversation with the patient and their family on a case-by-case basis about the risks and benefits of treatment.

Sleep Disturbances in Children With Atopic Dermatitis: A Scoping Review.

Atopic dermatitis (AD) is associated with various quality of life concerns including poor sleep. Sleep impairments in children with AD are associated with increased risk of short stature, metabolic syndrome, mental illness and neurocognitive dysfunction. Although the association between AD and sleep disturbance is well established, the specific types of sleep disturbance in pediatric AD patients and their underlying mechanisms are not fully understood. A scoping literature review was performed to characterize and summarize the types of sleep disturbance in children (less than 18 years of age) with AD. 31 papers met inclusion criteria and extracted data were analyzed in an iterative manner. Two types of sleep disturbances were found to be more prevalent in pediatric AD patients in comparison to controls. One category was related to loss of sleep (increased frequency or duration of awakenings, increased sleep fragmentation, delayed sleep onset, decreased total sleep duration, and decreased sleep efficiency). Another category was associated with unusual behaviors during sleep (restlessness/limb movement/scratching, sleep-disordered breathing including obstructive sleep apnea and snoring, nightmares, nocturnal enuresis and nocturnal hyperhidrosis). Some mechanisms underlying these sleep disturbances include pruritus and induced scratching and increased proinflammatory markers induced by sleep loss. Sleep disturbance appears to be associated with AD. We recommend clinicians to consider interventions that may reduce sleep disturbances in children with AD. Further investigation of these sleep disturbances is needed to elucidate pathophysiology, develop additional treatments, and reduce negative impacts on the health outcomes and quality of life in pediatric AD patients.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

BACKGROUND: Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. OBJECTIVE: The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. METHODS: Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (< 60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. RESULTS: In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. LIMITATIONS: There were fewer patients in the ≥ 60-year-old group; post hoc analyses. CONCLUSION: Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged < 60 years. Safety was consistent with the known dupilumab safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).