Abrocitinib efficacy and safety in moderate-to-severe atopic dermatitis by race, ethnicity, and Fitzpatrick skin type.

BACKGROUND: Response to abrocitinib treatment for moderate-to-severe atopic dermatitis (AD) has not been evaluated across racial and ethnic subpopulations. OBJECTIVE: To assess the efficacy and safety of abrocitinib on the basis of patient race, ethnicity, and Fitzpatrick skin type (FST). METHODS: Data were pooled post hoc from patients treated with abrocitinib 200 mg, 100 mg, or placebo in 3 monotherapy trials (NCT02780167, NCT03349060, and NCT03575871). Race and ethnicity were self-reported; FST was determined by study investigators. Evaluations through Week 12 include the following: (1) Investigator's Global Assessment of clear or almost-clear skin; (2) greater than or equal to 75% improvement in Eczema Area and Severity Index or SCORing AD; (3) a greater-than-or-equal-to 4-point improvement in Peak Pruritus Numerical Rating Scale score; (4) least squares mean changes in Dermatology Life Quality Index and Patient-Oriented Eczema Measure scores; and (5) treatment-emergent adverse events. RESULTS: The sample comprised 628 White, 204 Asian, and 83 Black patients; 37 were Hispanic or Latino; 624 had FST I to III and 320 had FST IV to VI. Treatment with either abrocitinib dose was associated with greater proportions of patients achieving Investigator's Global Assessment of clear or almost-clear skin, ≥ 75% improvement in Eczema Area and Severity Index, ≥ 75% improvement in SCORing AD, and a ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale, or greater score changes from baseline in Dermatology Life Quality Index and Patient-Oriented Eczema Measure vs placebo regardless of race, ethnicity, or FST. Dose-response was most prominent in White patients. In Black patients, the effects of the 2 doses were similar. Treatment-emergent adverse events were more common in White and Black than in Asian patients. CONCLUSION: Abrocitinib was more efficacious than placebo across the racial and ethnic groups and ranges of phototypes analyzed. Studies with increased representation of populations of color are warranted to elucidate potential variations in response across diverse populations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02780167 (phase 2b), NCT03349060 (phase 3 MONO-1), and NCT03575871 (phase 3 MONO-2).

Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial.

BACKGROUND: Phase 3 trials have assessed efficacy of abrocitinib versus placebo in moderate-to-severe atopic dermatitis, a common immunoinflammatory skin disease. This study assessed the efficacy and safety of abrocitinib versus dupilumab. METHODS: This randomised, double-blind, double-dummy, active-controlled, parallel-treatment, phase 3 trial enrolled adults with moderate-to-severe atopic dermatitis who requir=ed systemic therapy or had inadequate response to topical medications. Participants were enrolled from 151 sites, located in Australia, Bulgaria, Canada, Chile, Finland, Germany, Hungary, Italy, Latvia, Poland, Slovakia, South Korea, Spain, Taiwan, and the USA. These participants were then randomly assigned (1:1) with block randomisation to receive oral abrocitinib (200 mg per day) or subcutaneous dupilumab (300 mg every 2 weeks) for 26 weeks. Participants were required to apply topical corticosteroids (medium or low potency), topical calcineurin inhibitors, or a topical phosphodiesterase 4 inhibitor to active lesion areas. Primary endpoints were response based on achieving a 4 point or higher improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 2 and a 90% or better improvement in Eczema Area and Severity Index (EASI-90) at week 4. Family-wise type 1 error was controlled via a sequential multiple-testing procedure (two sided, α=0·05). Randomly assigned participants who received at least one dose of study intervention were included in the efficacy and safety analysis sets. This trial was completed on July 13, 2021 (NCT04345367). FINDINGS: Between June 11, 2020, and Dec 16, 2020, 940 patients were screened and 727 were enrolled (362 in the abrocitinib group and 365 in the dupilumab group). Compared with dupilumab, a larger proportion of patients treated with abrocitinib reached the primary outcomes, PP-NRS4 at week 2 (172 [48%] of 357, 95% CI 43·0-53·4 vs 93 [26%] of 364, 21·1-30·0; difference 22·6%, 15·8-29·5; p<0·0001), and EASI-90 at week 4 (101 [29%] of 354, 23·8-33·2 vs 53 [15%] of 364, 10·9-18·2; difference 14·1%, 8·2-20·0; p<0·0001). Treatment-emergent adverse events were reported by 268 (74%) of 362 patients treated with abrocitinib and by 239 (65%) of 365 patients treated with dupilumab. Two non-treatment-related deaths occurred in the abrocitinib group. INTERPRETATION: Abrocitinib 200 mg per day was more efficacious than dupilumab in adults with moderate-to-severe atopic dermatitis on background topical therapy in inducing early reductions of itch and atopic dermatitis disease signs. Both treatments were well tolerated over 26 weeks. FUNDING: Pfizer.

Regression of diffuse B-cell lymphoma of the leg with intralesional gentian violet.

In this case report, a patient of primary cutaneous diffuse B-cell lymphoma, leg type was treated with intralesional gentian violet as she was judged to be too medically fragile for conventional chemotherapy due to advanced age and multiple serious comorbidities. Gentian violet (crystal violet/hexamethyl pararosaniline) is a triphenylmethane dye. It has been shown to have an inhibitory effect on NADPH oxidase, an enzyme family which is found in abundance in reactive oxygen-driven tumors such as melanoma and lymphoma. We hypothesize that intralesional gentian violet treatment caused signalling changes in the lymphoma which allowed for immune clearance of the lymphoma. Complete resolution of the patient's lesion was noted on a follow-up visit.

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Atopic dermatitis (AD, also called atopic eczema) is a skin disease that that can affect a person for a long time and causes red or flaky skin that can be itchy and uncomfortable. Healthcare providers can prescribe medicated creams and ointments to reduce the visible signs and symptoms of AD, but these treatments are not always enough to keep it under control. A new medicine called abrocitinib is taken every day as a tablet. Abrocitinib works by slowing a part of the body's defense mechanism, called immune response, that is not functioning properly in AD. The clinical study described in this plain language summary, called JADE DARE, investigated how well and how safely 26 weeks of treatment with abrocitinib worked in adults with AD compared to an injected medicine, called dupilumab, that is also approved for AD. WHAT WERE THE RESULTS?: The study showed that abrocitinib was more effective than dupilumab in providing itch relief after 2 weeks. In addition, people who were taking abrocitinib for 4 and 16 weeks experienced greater improvement in the visible skin signs of AD than people who were taking dupilumab. The number of people who had health complaints while taking abrocitinib was similar to the number of people who had health complaints while taking dupilumab. Most of these complaints were minor. WHAT DO THE RESULTS MEAN?: Abrocitinib was more effective than dupilumab in quickly improving the signs and symptoms of moderate or severe AD in people who did not show improvement with prescribed medications like creams or ointments. Clinical Trial Registration: NCT04345367 (ClinicalTrials.gov).

Resource utilization and quality of life associated with congenital ichthyoses.

We explored resource utilization (ResUtil) and quality of life (QOL) associated with congenital ichthyoses (CI). Subjects completed an online survey related to clinical severity, demographics, ResUtil, and QOL as measured according to the Dermatology Life Quality Index (DLQI). Validated Likert scales were used to evaluate severity of hyperkeratosis, erythema, and alopecia. ResUtil was determined according to time spent daily treating CI symptoms (TimeTx) and number of ichthyosis-related dermatology visits (DermVisits) per year. We used linear regression to investigate predictors of a transformed DLQI (sqrtDLQI) and logistic regression for ResUtil. Of 235 subjects, 60.2% were female, 83.8% were Caucasian, 42.3% had a family history (FamHx) of CI, and the mean age was 28.7 years (SD 20.3). Predictors for worse QOL were hyperkeratosis severity (ß = 0.27, p < 0.01), erythema (ß = 0.27, p < 0.01), TimeTx (ß = 0.21, p < 0.01), ichthyosis type (ß = 0.09, p < 0.01), and age (ß = 0.01, p = 0.02). Predictors for DermVisits were hyperkeratosis severity (odds ratio [OR] = 1.38, 95% confidence limit [CL] = 1.01, 1.87), FamHx (OR = 0.28, 95% CL = 0.09, 0.85), age (OR = 0.97, 95% CI = 0.96, 0.99), and alopecia severity (OR = 1.43, 95% CL = 1.12, 1.82). Predictors for treatment duration were erythema (OR = 1.35, 95% CL = 1.02, 1.78), age (OR = 0.98, 95% CL = 0.96, 0.99), and DLQI (OR = 1.09, 95% CL = 1.03, 1.15). Increased hyperkeratosis severity and erythema negatively impact QOL in the CI. Furthermore, increased disease severity predicted greater ResUtil, whereas increased age and FamHx predicted less ResUtil. Our findings suggest that better therapies and increased patient education may improve QOL and decrease ResUtil.

Reliable methods to evaluate the clinical severity of ichthyosis.

A reliable method for assessing ichthyosis severity has not been uniformly agreed upon. The objective of our study was to develop and validate a tool to measure the clinical severity of the congenital ichthyoses, the Congenital Ichthyoses Severity Index. A prospective study was performed to determine reliability of three Likert scales to evaluate clinical severity of ichthyosis. Thirty-eight subjects recruited from the Foundation for Ichthyosis and Related Skin Types National Conference were evaluated separately by two blinded investigators using the Likert scales. Subjects were then asked to evaluate themselves using these scales. Inter-rater reliability was determined between ratings provided by all three raters. Test-retest validation was conducted with 21 subjects who completed follow-up surveys 4 weeks later. Our severity scales had excellent inter-rater and test-retest reliability as determined by intraclass correlation coefficients (ICC >0.7), with the exception of our hyperkeratosis scale, which demonstrated moderate test-retest reliability (ICC = 0.4). This pilot study provides a promising method for evaluating clinical severity of the congenital ichthyoses, one easily employed by both physicians and patients. Future epidemiologic studies may benefit from use of this instrument, as well as studies evaluating emerging therapies for ichthyosis.

Annual direct and indirect health costs of the congenital ichthyoses.

The aim of this study is to estimate annual, per patient, health care costs for congenital ichthyoses (CI). We conducted a cost analysis through an online survey posted on the Foundation for Ichthyosis and Related Skin Types Website. We assessed cutaneous disease severity, via the previously validated Congenital Ichthyosis Severity Index (CISI), demographics, and CI type. We estimated direct health care costs: prescription and over-the-counter medications, outpatient visits, and emergency department and hospital visit costs; and indirect costs: earnings lost owing to absences from work because of CI-related illness. The CI subjects of our study (n=224) consumed a mean (SD) of $3,192 ($7,915) annually. Direct costs accounted for 90%, whereas indirect costs accounted for 10%. These costs resulted in an estimated annual cost of $37 MM/year (excluding ichthyosis vulgaris) of which $17 MM is borne out-of-pocket by patients. Depending on the CI diagnosis, patients were responsible for 30-51 cents of every dollar of mean annual medical care costs. Our estimated annual CI costs are comparable to cutaneous lymphoma. More effective treatments for CI would help minimize this burden. Traditional insurance products do not appear to substantially alleviate the financial burden of disease, as a significant amount is from out-of-pocket expenses.

Quality of life of cutaneous disease in the ectodermal dysplasias.

The ectodermal dysplasias are a complex, heritable group of syndromes that affect derivatives of ectoderm. The dermatologist plays an important role in ectodermal dysplasias as the visible defects of skin, hair, and nails are often recognized first. Our objective was to examine how quality of life relates to the degree of skin involvement in ectodermal dysplasias. Subjects (n = 42) with ectodermal dysplasias were surveyed at national and regional conferences hosted by National Foundation for Ectodermal Dysplasias on July 26 to 28, 2007 and November 17, 2007. Severity of hypohidrosis, alopecia, and fingernail involvement were measured using validated Likert scales. The quality of life was measured using the Children's Dermatology Life Quality Index in children, and the Skindex-29 and RAND Short Form-36 in adults. The severity for all subjects (n = 42) was greatest for hypohidrosis, which clinically translated into "little ability to sweat." We found that the greatest impact on quality of life was related to the actual symptoms of ectodermal dysplasias, which is not surprising as almost all participants reported skin involvement (93%), most likely related to hypohidrosis, atopic dermatitis, skin erosions and infections. The symptoms of ectodermal dysplasias may also be related to the nail involvement, as manifested by dystrophic or fragmented nails. Alopecia did not play a significant role in the quality of life burden. The challenge of providing proper skin care emphasizes the benefit of dermatologic involvement, and the need for increased recognition and enhanced awareness of the cutaneous burden in ectodermal dysplasias.

Hyperhidrosis and its impact on those living with it.

Sweating plays a vital role for humans. However, excessive sweating, also called hyperhidrosis, is a condition resulting in sweating beyond what is physiologically necessary. The increased rate of sweating is not caused by external stimuli or temperature fluctuations, as with an individual without hyperhidrosis. Hyperhidrosis affects approximately 4.8% of Americans. Primary hyperhidrosis, a specific classification of the disease, primarily affects younger adults aged 18 to 39 years, and it often has a genetic component. Living with hyperhidrosis presents many challenges and impacts numerous aspects of daily life. Patients with hyperhidrosis are impacted in their social and professional lifestyles, as well as their mental and emotional health. These negative effects, which have been studied, lead to a lower quality of life (QOL) in this population. Additionally, constant moisture from sweating can lead to skin maceration. This increases the risk of skin conditions such as athlete's foot and more severe conditions such as bacterial infections or pitted keratolysis. Study results report a nearly 30% greater risk of skin infections in patients with hyperhidrosis compared with healthy controls. This section of the continuing education supplement will examine the pathophysiology and clinical severity of hyperhidrosis and identify the comorbidities and QOL challenges associated with this condition.

Effects of total-body digital photography on cancer worry in patients with atypical mole syndrome.

IMPORTANCE: Cancer worry about developing melanoma in at-risk patients may affect one's quality of life and adherence to screening. Little is known about melanoma-related worry in patients with atypical mole syndrome (AMS). OBJECTIVES: To quantify levels and elucidate predictors of worry related to developing melanoma in patients with AMS and to determine whether total-body digital photography (TBDP) in pigmented lesion clinics (PLCs) reduces worry. DESIGN, SETTING, AND PARTICIPANTS: In this pretest-posttest study, patients with AMS from PLCs at 2 academic medical centers were recruited from June 1, 2005, through October 31, 2008, to answer questions about cancer worry before and after undergoing TBDP. Questionnaires used included the new melanoma and recurrent melanoma Revised Impact of Event Scale (RIES), the Melanoma Worry Scale (MWS), the Hospital Anxiety and Depression Scale, and the Life Orientation Test. INTERVENTIONS: All patients underwent TBDP. MAIN OUTCOMES AND MEASURES: Changes in the MWS and new melanoma RIES scores. RESULTS: A total of 138 patients completed baseline questionnaires; 108 patients (78.3%) completed questionnaires after TBDP. Baseline levels of worry were low and reduced further after TBDP. In patients with a personal history of melanoma, worry was reduced on all scales. In patients without a personal history of melanoma, only the new melanoma RIES score was significantly decreased. Predictors of baseline MWS scores include female sex, personal history of melanoma, and higher Hospital Anxiety and Depression Scale scores, adjusted for demographics, family history of melanoma, and Life Orientation Test scores. Adjusted predictors of the baseline new melanoma RIES score were similar but also included lower educational level and did not include sex. CONCLUSIONS AND RELEVANCE: Patients with AMS have low levels of melanoma-related worry, which is similar to data from other populations at high risk of cancers. We found that TBDP is a clinically useful tool that can be used in PLCs to help decrease worry about developing melanoma in at-risk patients.

Utilization and rationale for the implementation of total body (digital) photography as an adjunct screening measure for melanoma.

The primary objective of our study was to update the prevalence of total body photography (TBP) utilization and the rationale for its implementation as an adjunctive screening measure by academic dermatologists across the USA, and investigate the emergence of total body digital photography (TBDP). Our secondary objective was to further examine how TBP/TBDP is being incorporated into the dermatology screening examination in academic pigmented lesion clinics. A questionnaire was mailed to 113 dermatology departments across the USA. About 43% (49/113) of surveyed departments responded. TBP was used by 67% (33/49) of the respondents. Of these respondents, 33% (11/33) used TBDP alone, 33% (11/33) used TBDP in combination with nondigitally based TBP, and 33% (11/33) used nondigital TBP with print photos. The three most frequently cited reasons for the use of full-body baseline photographs were that they reduced patient anxiety, led to fewer biopsies, and helped to find melanoma early in the curable stage. Respondents who did not use full body baseline photographs cited logistical constraints as the number one reason, followed by perceived lack of utility. In conclusion, our study shows that there is a significant number of academic dermatologists using TBP/TBDP. However, this study also shows that there are conflicting beliefs among academic dermatologists concerning the efficacy of TBP/TBDP. At this point with a documented growing trend in utilization of TBP, more studies are needed to evaluate the efficacy of this screening adjunct to diagnose melanoma early and positively impact survival because of early diagnosis.