Ian Landells

Etanercept treatment for children and adolescents with plaque psoriasis.

BACKGROUND Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis. METHODS In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physicians global assessment of clear or almost clear of disease, and safety assessments. RESULTS At week 12, 57% of patients receiving etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physicians global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001). At week 36, after 24 weeks of open-label etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label etanercept; all resolved without sequelae. CONCLUSIONS Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819 [ClinicalTrials.gov].).

Web-based continuing medical education (II): Evaluation study of computer-mediated continuing medical education

Background: Over the years, various distance learning technologies and methods have been applied to the continuing medical education needs of rural and remote physicians. They have included audio teleconferencing, slow scan imaging, correspondence study, and compressed videoconferencing. The recent emergence and growth of Internet, World Wide Web (Web), and compact disk read‐only‐memory (CD‐ROM) technologies have introduced new opportunities for providing continuing education to the rural medical practitioner. This evaluation study assessed the instructional effectiveness of a hybrid computer‐mediated courseware delivery system on dermatologic office procedures. Methods: A hybrid delivery system merges Web documents, multimedia, computer‐mediated communications, and CD‐ROMs to enable self‐paced instruction and collaborative learning. Using a modified pretest to post‐test control group study design, several evaluative criteria (participant reaction, learning achievement, self‐reported performance change, and instructional transactions) were assessed by various qualitative and quantitative data collection methods. Results: This evaluation revealed that a hybrid computer‐mediated courseware system was an effective means for increasing knowledge (p <.05) and improving self‐reported competency (p <.05) in dermatologic office procedures, and that participants were very satisfied with the self‐paced instruction and use of asynchronous computer conferencing for collaborative information sharing among colleagues.

Web-based continuing medical education (I): Field test of a hybrid computer-mediated instructional delivery system

Background: The Internet and the World Wide Web (the Web) present exciting new possibilities for distributing educational materials at a distance and facilitating collaborative learning among geographically isolated physicians. This article provides a brief overview of the Web as an instructional delivery platform and discusses its strengths and weaknesses as a potential medium for enhancing distance learning opportunities for rural and remote physicians. It also describes an innovative hybrid instructional delivery model that was field tested by the Telemedicine Centre to determine its efficiency and effectiveness for providing Web‐based instruction. A hybrid model merges the Web and CD‐ROMs (compact disk read‐only memory) to use several of the more valuable instructional components of Web‐based education (i.e., multimedia, interactive forms, hypermedia, and computer‐mediated communications). The results of the field test indicate that the hybrid delivery model was an efficient means for delivering computer‐mediated continuing medical education instruction on dermatologic office procedures to a group of rural physicians in low telecommunication bandwidth regions.

High prevalence of psoriatic arthritis in a cohort of patients with psoriasis seen in a dermatology practice.

Background/Objectives: The prevalence of psoriatic arthritis (PsA) is expected to range from 5 to 40% in individuals with psoriasis. The objective of this study was to quantify the prevalence of PsA in psoriasis patients seen in a dermatology practice and to define their characteristics using the validated Psoriatic Arthritis Screening Questionnaire (PASQ). Methods: Patients with definite plaque psoriasis (as determined by a dermatologist) completed the self-administered PASQ tool, and patients with a score ≥ 7 or ≥ 9 were assessed by a rheumatologist to ascertain the diagnosis of PsA according to the CASPAR (Classification Criteria for Psoriatic Arthritis) criteria. Results: Using a PASQ cutoff of 7, the estimated prevalence (95% CI) of PsA was 40.9% (29.0–52.8%), whereas a prevalence (95% CI) of 36.4% (24.8–48.0%) was estimated when a PASQ cutoff of 9 was used. Conclusion: Our estimated prevalence of PsA in psoriasis patients from a population of patients drawn from a dermatology practice is greater than most previous estimates. This finding illustrates the importance of screening for PsA in psoriasis patients as this comorbidity may affect the course of treatment and, if left untreated, may have a profound effect on the disability and quality of life of a large number of psoriasis patients.

The electronic Psoriasis and Arthritis Screening Questionnaire (ePASQ): a sensitive and specific tool to diagnose psoriatic arthritis patients.

Background: We report on an electronic version of the Psoriatic Arthritis Screening Questionnaire (ePASQ), a sensitive and specific tool for diagnosis of psoriatic arthritis (PsA) in patients with plaque psoriasis. Objective: To validate the ePASQ against the original paper version. Method: The ePASQ scores 15 points on 10 weighted questions and a 68-joint diagram. Data were collected from a prospective cohort of 42 patients with early PsA meeting the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria and from 12 plaque psoriasis patients without PsA. Results: The receiver operating characteristic curves for the ePASQ group yielded an optimal 97.62% sensitivity and 75.00% specificity, for a cutoff score of 7. A cutoff point of 8 yielded 88.10% sensitivity and 75.00% specificity. Concordance of the paper and electronic scores was very high. Conclusion: The ePASQ is a sensitive and specific tool to screen for PsA. The simple electronic administration and automatic scoring minimize clinician involvement and increase the potential for wider distribution.

Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial

BACKGROUND Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis. METHODS This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries. Patients (aged ≥4 to <18 years) with severe plaque psoriasis who had not responded to topical therapy were randomly assigned with an interactive voice or web-response system (1:1:1) to receive adalimumab 0·8 mg/kg or 0·4 mg/kg subcutaneously at week 0, then every other week starting at week 1, or oral methotrexate once weekly (0·1-0·4 mg/kg) for 16 weeks. Randomisation was stratified by history of etanercept treatment, with a block size of three. Responders were withdrawn from treatment (for up to 36 weeks) and re-treated with adalimumab (for 16 weeks) if disease became uncontrolled. Ranked primary efficacy endpoints were the proportion of patients who achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75) score and clear or minimal physician global assessment (PGA) score at week 16, comparing adalimumab 0·8 mg/kg with methotrexate. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01251614, and has been completed. FINDINGS Between Dec 14, 2010, and Feb 5, 2015, 114 patients were randomly assigned to adalimumab 0·8 mg/kg (n=38), adalimumab 0·4 mg/kg (n=39) or methotrexate (n=37). At week 16, PASI75 was achieved in 22 (58%) of 38 patients in the adalimumab 0·8 mg/kg group compared with 12 (32%) of 37 patients in the methotrexate group (p=0·027). 23 (61%) of 38 patients in the adalimumab 0·8 mg/kg group and 15 (41%) of 37 in the methotrexate group achieved clear or minimal PGA (p=0·083). In the adalimumab 0·4 mg/kg group, 17 (44%) of 39 patients achieved PASI75 and 16 (41%) achieved clear or minimal PGA. The most frequent adverse events were infections (17 [45%] of 38 in the adalimumab 0·8 mg/kg group during initial treatment; 22 [56%] of 39 in the adalimumab 0·4 mg/kg group; 21 [57%] of 37 in the methotrexate group). Three serious adverse events were reported, all in patients in the adalimumab 0·4 mg/kg group, and were not judged to be related to study drug. INTERPRETATION Treatment with adalimumab 0·8 mg/kg in children and adolescents with severe plaque psoriasis provided significant improvements in PASI75 and a non-significant increase in the proportion of patients who achieved clear or minimal PGA compared with methotrexate. No new safety risks were identified. FUNDING AbbVie.

Efficacy and safety of etanercept in children and adolescents aged ≥ 8 years with severe plaque psoriasis

Etanercept, a fully human soluble tumor necrosis factor (TNF)-alpha receptor, is approved in Europe for treatment of severe plaque psoriasis in children > or = 8 years. The efficacy and safety of etanercept for this population was evaluated in a retrospective analysis of a previous study, which included 211 children (4-17 years) with psoriasis involving > or = 10% body surface area and Psoriasis Area and Severity Index (PASI) > or = 12. In this subanalysis, subjects aged 8-17 years received once-weekly subcutaneous etanercept 0.8 mg/kg (< or = 50 mg) or placebo in double-blind fashion for 12 weeks, followed by 24 weeks of open-label etanercept. Baseline demographics and disease characteristics were similar across treatment arms (etanercept n = 95, placebo n = 97). At week 12, 54.7% subjects receiving etanercept versus 11.3% receiving placebo achieved 75% or greater improvement in PASI (PASI 75) compared with baseline (p < 0.001). PASI 50, PASI 90, and static Physician Global Assessment of psoriasis followed a similar pattern (p < 0.001). Efficacy during the open-label phase was sustained through Week 36. Exposure-adjusted rates of adverse events for etanercept were similar or lower than those for placebo. No appreciable differences were noted in the efficacy and safety profiles between the subjects aged > or = 8 years in this analysis and those in the original study population aged 4-17 years. In conclusion, etanercept provided significant, sustained improvement in disease severity and was well tolerated in children > or = 8 years with severe plaque psoriasis.

Update on alefacept safety.

Background: Alefacept has been demonstrated in clinical trials to be an effective, safe, and well-tolerated treatment strategy when used alone or in combination with other antipsoriatic therapies in patients with chronic plaque psoriasis. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, Canadian phase IV registry evaluating the efficacy and safety of alefacept, alone or in combination with other antipsoriatic therapies, in patients with psoriasis. Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept followed by an off-treatment period, typically lasting 12 or more weeks. Prospective follow-up was at least 60 weeks, depending on when patients presented for retreatment. Safety data collected throughout the study included the incidence of serious adverse events (SAEs), dosing suspensions, and withdrawals owing to adverse events. Results: Twelve SAEs were reported in psoriasis patients treated with at least one course of alefacept, with only one considered to be possibly related to the study drug. Approximately one-quarter of patients missed at least one dose of alefacept during the course of the study. A total of 291 doses of alefacept were missed, representing almost 4% of the total doses administered in this group of patients. Low CD4+ count was the most frequent reason for missed doses; however, no patient had persistently low CD4+ counts requiring permanent discontinuation of alefacept treatment. Seven patients in the AWARE registry discontinued treatment with alefacept, with the most common reason being patient request. Conclusion: The AWARE study supports the safety of alefacept used alone or in combination with other antipsoriatic therapies, in a broad population of real-world chronic plaque psoriasis patients in Canada.

Patterns of Combination Therapy with Alefacept for the Treatment of Psoriasis in Canada in the AWARE Study

Background: Evidence from clinical trials supports the use of alefacept for the treatment of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept. Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept treatment followed by a period of at least 12 weeks off-treatment. The use of combination therapy with alefacept in a real-world population of psoriasis patients is presented here, including the types of psoriasis therapies received by patients at the time of enrolment, reasons for initiating alefacept, and discontinuation or dosage reduction of concomitant therapy. Results: The majority of patients were receiving other antipsoriatic therapies at the time of enrolment into the AWARE study, most commonly topical therapy, systemic agents, or phototherapy. Most patients were receiving monotherapy prior to the initiation of alefacept. There was little change in the use of topical therapies with alefacept at 24 weeks, whereas a substantial proportion of patients were able to reduce or discontinue concomitant systemic therapies and/or phototherapy. The use of combination therapy regimens was relatively consistent across the country and by age groups, although younger patients were prescribed systemic agents more often than older patients. Conclusion: Alefacept is commonly added to other antipsoriatic therapies in a broad population of real-world chronic plaque psoriasis patients in Canada and may allow for dosage reduction or discontinuation of concomitant systemic agents or phototherapy.

The AWARE Study: Methodology and Baseline Characteristics

Background: Alefacept was the first biologic therapy approved by Health Canada for the treatment of moderate to severe chronic plaque psoriasis and is used either alone or as part of combination therapy. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational phase IV Canadian study of psoriasis patients treated with alefacept. This studys main goals were to develop a shared, real-time, national clinical database to support best practice and optimize the care of patients receiving alefacept and to gain an understanding of how alefacept is used in Canadian clinical practice. Baseline patient demographic data are described herein. Methods: Patients with chronic plaque psoriasis were enrolled from 37 clinics across Canada. Subjects received at least one course of alefacept treatment followed by a period of at least 12 weeks off treatment and were prospectively followed for at least 60 weeks. Baseline assessments included patient demographics, relevant medical history, psoriasis and treatment history, reasons for initiating alefacept, enrolling physicians initial alefacept treatment plan and strategy, percent body surface area (BSA) involvement with psoriasis, and physicians baseline assessment of disease control. Subsequent assessments at each follow-up visit included the patients response and the physicians assessment. Results: A total of 426 adult patients with predominantly chronic plaque psoriasis, with or without other types of psoriasis, were enrolled into the AWARE registry. Patients generally had moderate to severe psoriasis, with more than half (55.8%) having little or no disease control at baseline as assessed by their clinician, and 77% had > 10% BSA involvement with psoriasis. All patients in the AWARE patient population were receiving one or more treatments for psoriasis prior to or at the time of enrolment, and the majority continued to receive concomitant treatments at the time of study enrolment. Conclusion: The AWARE registry enrolled a broad group of real-world patients with chronic plaque psoriasis treated with alefacept in clinical practices across Canada.