Long-term safety and efficacy of a fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis: phase 3 open-label study.

BACKGROUND: The topical corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (TAZ) are effective in psoriasis treatment. To mitigate adverse cutaneous reactions observed with monotherapy, a fixed- combination HP 0.01%/TAZ 0.045% lotion has been developed for the treatment of plaque psoriasis in adults. OBJECTIVES: To investigate the long-term safety, efficacy and maintenance of response with HP/TAZ lotion. METHODS: This was a 1-year, multicentre, open-label study in 555 adults with psoriasis [Investigator's Global Assessment (IGA) score of 3 ('moderate') or 4 ('severe') and body surface area (BSA) of 3-12% at baseline]. HP/TAZ was administered once daily for 8 weeks and then intermittently as needed in 4-week intervals for up to 1 year based on achievement of treatment success [IGA score of 0 ('clear') or 1 ('almost clear')]. Maximum continuous exposure was 24 weeks. RESULTS: Of 550 participants with postbaseline safety data, 318 (57.8%) achieved treatment success during the study. Of those, 54.4% achieved treatment success within the first 8 weeks; retreatment was not required for >4 weeks in over half (55.3%), and 6.6% did not require any retreatment. Among participants enrolled for the full 52 weeks, 77.5% maintained BSA ≤5% on treatment. There were marked improvements in severity of itching, dryness and burning/stinging over the study course. The most common treatment-related adverse events were application site reactions of dermatitis, pruritus, pain and irritation. CONCLUSIONS: Fixed-combination HP/TAZ lotion provided maintained efficacy with a favourable tolerability and safety profile, supporting its use for the long-term treatment and management of moderate-to-severe plaque psoriasis.

Continued treatment with secukinumab is associated with high retention or regain of response.

BACKGROUND: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. OBJECTIVES: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. METHODS: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) ('excellent'), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 ('good') and < PASI 75 ('insufficient'). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in 'insufficient' response. All comparisons are descriptive. RESULTS: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. CONCLUSIONS: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic? Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add? To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.

The 2020 International Alliance for the Control of Scabies Consensus Criteria for the Diagnosis of Scabies.

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study.

BACKGROUND: ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate-to-severe AD. Methods A total of 36 patients with moderate-to-severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28-day period (20 mg, 40 mg and 80 mg once daily). RESULTS: ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg -1·3 ± 2·1, P = 0·81; 40 mg -3·1 ± 2·7, P = 0·27; 80 mg -4·7 ± 2·1, P = 0·01; placebo -1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose-dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis-associated biomarker E selectin/SELE. CONCLUSIONS: In patients with moderate-to-severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.

Itch: an under-recognized problem in psoriasis.

Psoriasis has historically been considered a nonpruritic dermatosis, in contrast with atopic dermatitis. Thus, itch has often been underappreciated and overlooked in psoriasis. However, increasing evidence over the past decade has shown that itch can be one of the most prevalent and burdensome symptoms associated with psoriasis, affecting almost every patient to some degree. Itch can involve the entire body, although it predominantly affects the legs, hands, back, body and especially the scalp. Uncontrolled itch can significantly impact all aspects of the well-being and quality of life of the patient. While there has been some progress in trying to better understand the pathophysiology of itch in psoriasis, more research effort and interest are needed. This under-recognition of itch in psoriasis is clearly reflected in the dearth of treatment options targeting itch despite significant advancement in treating the lesions themselves. Recently, however, clinical studies have begun to include itch as a study outcome. The resulting data have demonstrated concomitant antipruritic benefits and improved Psoriasis Area and Severity Index (PASI) scores with mainstay treatments for psoriasis, such as topical corticosteroids and vitamin D analogs, phototherapies, and various systemics and biologics. This article takes a closer look at this debilitating symptom, reviewing the available epidemiology data for psoriatic itch, presenting the current understanding of psoriatic itch pathophysiology and highlighting important clinical data for various treatment options for itch. Practical considerations for increasing the recognition of itch as well as improving its management in psoriasis are also provided.

Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND: PF-04965842 is an oral Janus kinase 1 inhibitor being investigated for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the efficacy, safety and tolerability of PF-04965842 in patients with moderate-to-severe plaque psoriasis. METHODS: Patients in this phase II, placebo-controlled study (NCT02201524) were randomized to receive placebo, 200 mg once daily (OD), 400 mg OD or 200 mg twice daily (TD) PF-04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities. RESULTS: Fifty-nine patients were randomized and received at least one dose of PF-04965842 or placebo. The estimated treatment effect (active -placebo PASI change from baseline) and 90% confidence interval at week 4 was -5·1 (-9·2 to -1·0), -5·6 (-9·6 to -1·6) and -10·0 (-14·2 to -5·8) for the 200 mg OD, 400 mg OD and 200 mg TD groups, respectively. At week 4, the proportion of patients achieving PASI 75 was 17% for the placebo and 200 mg OD groups, 50% for the 400 mg OD group and 60% for the 200 mg TD group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg TD group compared with the OD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported. CONCLUSIONS: These results suggest that treatment with PF-04965842 improves symptoms and is well tolerated in patients with moderate-to-severe psoriasis.

Apremilast for the treatment of moderate-to-severe palmoplantar psoriasis: results from a double-blind, placebo-controlled, randomized study.

BACKGROUND: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. OBJECTIVES: The main objectives of this double-blind, placebo-controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of apremilast for the treatment of moderate-to-severe palmoplantar psoriasis. METHODS: A total of 100 patients with moderate-to-severe palmoplantar psoriasis were randomized to either apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. RESULTS: There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition, apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (apremilast: -7.4 ± 7.1; placebo: -3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (apremilast: -4.3 ± 5.1; placebo: -0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (apremilast: -11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). CONCLUSION: Despite the absence of a significant difference between apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that apremilast may have a role in the treatment of moderate-to-severe palmoplantar psoriasis.

Photodynamic therapy with methyl aminolaevulinate 80 mg g(-1) for severe facial acne vulgaris: a randomized vehicle-controlled study.

BACKGROUND: Severe acne vulgaris has limited therapeutic options. OBJECTIVES: To evaluate photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL, 80 mg g(-1) ) as the photosensitizer in severe facial acne. METHODS: A double-blind, randomized, vehicle-controlled multicentre trial in 153 patients (aged 12-35 years) with severe facial acne [Investigator's Global Assessment (IGA) score 4; 25-75 inflammatory lesions with ≤ 3 nodules; 20-100 noninflammatory lesions]. Treatment (four treatments 2 weeks apart) involved incubation with MAL (n = 100) or vehicle cream (n = 53) for 1·5 h under occlusion, then illumination (635-nm red light, total dose 37 J cm(-2) ). IGA assessment and standardized lesion counts were performed before each treatment and 12 weeks after the first treatment. Treatment success was defined as improvement from baseline in IGA by ≥ 2 grades at 12 weeks. Safety assessments were for pain (10-cm visual analogue scale, immediately after illumination), erythema (four-point rating scale) and adverse events. RESULTS: At 12 weeks, PDT using MAL 80 mg g(-1) reduced inflammatory lesions vs. vehicle PDT (mean change -15·6 vs. -7·8, P = 0·006; mean percentage change -37·3% vs. -16·2%, P = 0·003). However, noninflammatory lesions did not decrease significantly (mean change -11·8 vs. -10·7, P = 0·85; mean percentage change -28·6% vs. -24·9%, P = 0·72). Treatment success rates were greater with MAL-PDT 80 mg g(-1) (44% vs. 26%, P = 0·013). Pain was low and manageable by briefly pausing illumination. There was similar pain or erythema with successive treatments. CONCLUSIONS: PDT using topical MAL 80 mg g(-1) and red light may offer promise for severe acne vulgaris.

Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. CONCLUSION: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.

Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States.

BACKGROUND: Psoriasis is associated with risk of malignancy. Some psoriasis treatments may increase the risk of hospitalized infectious events (HIEs). OBJECTIVES: To evaluate rates of malignancies and HIEs in patients with psoriasis. METHODS: This retrospective cohort study utilized data from MarketScan(®) databases. Cohorts included adult general population (GP), patients with psoriasis, and patients with psoriasis treated with nonbiologics, adalimumab, etanercept, infliximab or phototherapy. Outcomes included incidence rates (IRs) per 10 000 person-years observation (PYO) for all malignancies excluding nonmelanoma skin cancer (NMSC), lymphoma, NMSC, and per 10 000 person-years of exposure (PYE) for HIEs. RESULTS: Incidence rates [95% confidence interval (CI)] for all malignancies except NMSC were 129 (127-130) and 142 (135-149) for GP (PYO = 51 071 587) and psoriasis (PYO = 119 432) cohorts, respectively; 10·9 (10·5-11·3) and 12·9 (10·9-14·8) for lymphoma; and 145 (144-147) and 180 (173-188) for NMSC. Rates for all malignancies excluding NMSC were similar among treatments but variable for lymphoma and NMSC. IRs (95% CI) for HIEs were 332 (256-408) for the nonbiologic cohort (PYE = 3528); 288 (206-370) for etanercept (PYE = 6563); 325 (196-455) for adalimumab (PYE = 2772); 521 (278-765) for infliximab (PYE = 1058); and 334 (242-427) for phototherapy (PYE = 1797). IRs for HIEs were lowest for etanercept and higher in patients on baseline systemic corticosteroids across treatment cohorts. CONCLUSIONS: Malignancy rates were higher in patients with psoriasis than the GP, but these treatments did not appear to increase malignancy risk.

A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.

BACKGROUND: Many immune-mediated disorders, including psoriasis, involve cytokine signalling via Janus kinase (JAK) enzymes. ASP015K (also designated JNJ-54781532), a novel oral JAK inhibitor, has shown moderate selectivity for JAK3 over JAK1 and JAK2 in enzyme assays. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of escalating, sequentially grouped, doses of ASP015K vs. placebo in patients with moderate-to-severe psoriasis. METHODS: This phase 2a multicentre, double-blind, randomized, placebo-controlled study (NCT01096862) enrolled 124 patients with moderate-to-severe plaque psoriasis. Five sequential ASP015K cohorts were enrolled, consisting of four twice-daily dosing groups (10, 25, 60, 100 mg) and one once-daily dosing group (50 mg) for 6 weeks. RESULTS: The primary efficacy end point [mean change in Psoriasis Area and Severity Index score from baseline to end of treatment (EOT; day 42)] significantly favoured ASP015K (overall treatment effect; P < 0.001) vs. placebo, with greater improvements at higher doses. By EOT, the secondary end points [Physician Static Global Assessment (PSGA) score, percentage of patients achieving PSGA success, and change in percentage, body surface area (BSA)] also improved with ASP015K vs. placebo (P < 0.001 for PSGA score and BSA; P < 0.01 for PSGA success). Epidermal thickness and proliferation decreased from baseline with ASP015K vs. placebo. ASP015K was generally well tolerated, with no serious adverse events (AEs) reported. CONCLUSIONS: In patients with moderate-to-severe psoriasis, ASP015K demonstrated dose-dependent improvements in clinical and histological measures of severity over 6 weeks of treatment. At all doses, ASP015K was well tolerated, with no reported serious AEs.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the U.S.A.: 2005-09.

BACKGROUND: Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated with the underlying inflammatory state, treatments or both. OBJECTIVES: To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations. METHODS: Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts [non-biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy] to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex. RESULTS: Among 40 987 patients with psoriasis, 11% were prescribed non-biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person-years) was 20% greater than the rate found in the general population (95/10 000 person-years). For NMSC, the psoriasis population rate (129/10 000 person-years) was 65% greater than the general population rate (78/10 000 person-years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person-years for the phototherapy group to 262/10 000 person-years for the other anti-TNF group. CONCLUSIONS: Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

BACKGROUND: Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. OBJECTIVES: To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. METHODS: This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. RESULTS: An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. CONCLUSIONS: In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

Development and validation of the Axillary Sweating Daily Diary: a patient-reported outcome measure to assess axillary sweating severity.

BACKGROUND: Hyperhidrosis is estimated to affect ~ 4.8% of the US population, and most patients experience a negative psychological impact. Here, we describe development and psychometric evaluation of a patient-reported outcome (PRO) measure to assess severity of axillary hyperhidrosis in clinical trials that meets current U.S. regulatory standards to support product approvals. METHODS: Three rounds of hybrid concept-elicitation/cognitive-debriefing qualitative interviews were conducted in adults with clinician-diagnosed primary axillary hyperhidrosis, followed by similar interviews in children/adolescents. The draft measure included diary items for presence, severity, impact and bothersomeness (basis of the Axillary Sweating Daily Diary [ASDD]), exploratory weekly impact items, and a single-item Patient Global Impression of Change (PGIC). Phase 2 (adults only) and phase 3 (adults and children ≥9 years) clinical trial data were utilized to evaluate measurement properties of the resulting draft measure: floor/ceiling effects, nonresponse bias, test-retest reliability, construct validity, and responsiveness were assessed. The primary concept of interest was axillary sweating severity (ASDD Item 2); however, additional supportive concepts were explored to allow for development of a comprehensive hyperhidrosis measure. RESULTS: Twenty-nine patient interviews were conducted (N = 21 adult and N = 8 children/adolescents), resulting in the ASDD (4 items, patients ≥16y) and child-specific ASDD-C (2 items ≥9y to <16y), as well as 6 Weekly Impact items and the PGIC (patients ≥16y). No floor/ceiling effects or response biases were identified. Consistency between hypothesized and observed correlation patterns between ASDD/ASDD-C items and other efficacy measures supported construct validity. Intraclass correlation coefficients supported test-retest reliability (0.91-0.93; Item 2). Large effect sizes (- 2.2 to - 2.4) demonstrated that the ASDD/ASDD-C Item 2 could detect changes in hyperhidrosis severity, supporting the measure's responsiveness. Patients perceiving a moderate improvement in symptoms on the PGIC experienced an average 3.8-point improvement on ASDD axillary sweating severity (Item 2); thus, a 4-point responder threshold was defined as a clinically meaningful change. CONCLUSIONS: Qualitative and quantitative evidence support the reliability and validity of the ASDD/ASDD-C and its use in the clinical evaluation of axillary hyperhidrosis treatments. Further evaluation of this measure in future research studies is warranted to demonstrate consistent performance across different axillary hyperhidrosis populations and in different study contexts.

A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.

BACKGROUND: Both tazarotene (a retinoid prodrug) and calcipotriene (a synthetic analog of vitamin D3) are effective in the treatment of plaque psoriasis, but no reports in the literature directly compare the efficacy and tolerability of these 2 drugs. Tazarotene is commonly used in conjunction with a topical corticosteroid. In this study, tazarotene was used with mometasone furoate (a synthetic corticosteroid), and the 2-drug regimen was compared with calcipotriene monotherapy. OBJECTIVE: This study was conducted to compare the efficacy and tolerability of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily with those of calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. METHODS: In this multicenter, investigator-blinded, parallel-group study, adult patients with chronic, stable plaque psoriasis affecting 5% to 20% of their body surface area were randomly allocated to receive up to 8 weeks of treatment with either tazarotene 0.1% gel once daily (in the evening) plus mometasone furoate 0.1% cream once daily (in the morning) or calcipotriene 0.005% ointment twice daily. Patients were assessed at baseline and at weeks 2, 4, and 8 of treatment. Patients who demonstrated complete clearance of plaque psoriasis after 2 or 4 weeks of treatment and those whose psoriasis had improved > or = 50% after 8 weeks of treatment entered a 12-week posttreatment follow-up phase during which they applied only moisturizer. Patients were reassessed after 4, 8, and 12 weeks of posttreatment follow-up. Physician-rated measures of efficacy included global improvement, plaque elevation, scaling, erythema, and percentage of body surface area involvement. Patient-rated assessments included efficacy of study treatment compared with previous therapies, comfort of treated skin, outlook for long-term control of psoriasis, and overall impression of treatment. RESULTS: Of 120 patients with moderate to severe psoriasis enrolled from 3 centers, 106 (88%) completed the study. No significant differences in baseline clinical variables were observed between the 2 groups. Twenty-seven patients (45%) in the tazarotene plus cortico-steroid group achieved marked improvement (> or = 75% global improvement) after 2 weeks of treatment compared with 15 patients (26%) in the calcipotriene group (P < or = 0.05). Between-group comparisons of the percentage of patients achieving complete or almost complete clearance (> or = 90% global improvement) did not reach statistical significance at any time point. When compared with the calcipotriene regimen, the tazarotene plus corticosteroid regimen resulted in significantly greater efficacy on trunk lesions in reducing plaque elevation (at the end of treatment and at week 4 of the posttreatment phase, P < or = 0.05), scaling (week 4 of treatment and week 4 of the posttreatment phase, P < or = 0.05), erythema (week 4 of treatment and at the end of treatment, P < or = 0.05), and percentage of body surface area involvement (weeks 2 and 4 of treatment, P < or = 0.01). In addition, the tazarotene plus corticosteroid regimen was significantly more effective in reducing the percentage of body surface area involvement in upper limb lesions (weeks 2 [P < or = 0.05] and 4 [P < or = 0.01] of treatment). Forty-two of 55 patients (76%) in the tazarotene plus corticosteroid group rated their medication as more or much more effective than previous therapies compared with 30 of 52 patients (58%) in the calcipotriene group (P < or = 0.05). Although adverse events (burning, pruritus, irritation, and erythema) occurred in a significantly greater proportion of patients who received tazarotene plus corticosteroid than in those who received calcipotriene (P < or = 0.05), 47 of 55 patients (85%) in both groups rated the comfort of their treated skin as "somewhat comfortable" or better and both groups had similar discontinuation rates due to treatment-related adverse events (3% and 5%, respectively). CONCL

Efficacy and safety of twice-daily augmented betamethasone dipropionate lotion versus clobetasol propionate solution in patients with moderate-to-severe scalp psoriasis.

This 2-week, randomized, multicenter, investigator-blinded, parallel-group study was conducted to compare the efficacy and safety of augmented betamethasone dipropionate 0.05% lotion and clobetasol propionate 0.05% solution in the treatment of moderate-to-severe scalp psoriasis among 197 (193 assessable) healthy adult patients with at least 20% scalp-surface involvement. The patients received one of two treatments applied twice a day for 2 weeks. Signs and symptoms were evaluated at baseline, after 3 days (day 4), and after weeks 1 (day 8) and 2 (day 15) of treatment. As early as 3 days after treatment, scaling and induration were improved significantly faster by betamethasone dipropionate than by clobetasol propionate. Both treatments also reduced erythema and pruritus. Patients receiving betamethasone dipropionate had a significantly greater mean percent improvement in total sign/symptom scores (P < or = 0.015) at all visits and better mean global clinical response scores at the early visits (days 4 and 8) (P < or = 0.017). At the end of the study, only mild disease was present in both groups. Adverse events were reported by 34.0% and 36.4% of patients receiving betamethasone dipropionate and clobetasol propionate, respectively. All events were transient, most were mild and local, and no discontinuations resulted. The effects of treatment on the hypothalamic-pituitary-adrenal axis were not measured. In conclusion, augmented betamethasone dipropionate lotion and clobetasol propionate solution were equally effective, but betamethasone dipropionate lotion provided a faster onset of relief for scaling and induration, which may enhance patient compliance and patient satisfaction with treatment.