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Oral Janus kinase inhibitors (JAKi), a class of advanced targeted systemic therapy, have demonstrated efficacy and safety in the treatment of moderate-to-severe atopic dermatitis (AD). Like other small molecules, oral JAKi have the potential for off-target effects including laboratory-related adverse events (AEs). Product labels for oral JAKi recommend an initial laboratory assessment and follow-up 4-12 weeks later to monitor for potential changes, based on evidence from clinical trials across therapeutic indications for oral JAKi, which may not reflect a population of moderate-to-severe AD patients typically seen in routine clinical practice. To address this gap, a panel of eight dermatologists with clinical and research experience with oral JAKi for the management of AD conducted a targeted review of the literature focused on key laboratory-related AEs associated with oral JAKi in the moderate-to-severe AD population. Based on the synthesis of evidence and informed opinion, a set of best practice statements related to fundamental standards of care and consensus recommendations on laboratory monitoring were suggested, and level of agreement was ascertained using a Likert scale from 0 to 100. There was a high level of agreement on three of the four suggested recommendations related to assessment and monitoring of key laboratory parameters and to dose reduction or switching in response to laboratory changes; there was a lower level of agreement related to the frequency of ongoing laboratory monitoring. Appropriate patient selection and laboratory assessment is an important strategy to mitigate the potential risks associated with oral JAKi when treating AD.
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BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.
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INTRODUCTION: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. METHOD: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. RESULTS: The expert panel reached consensus on 20 statements. CONCLUSION: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.
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Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Sistema de Registros , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Sistema de Registros/estadística & datos numéricos , Adulto , Canadá , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , América Latina , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunologíaRESUMEN
INTRODUCTION: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. METHODS: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). RESULTS: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16. CONCLUSIONS: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422.
Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 12 weeks. The extent of the improvements increased through weeks 46 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Insuficiencia del Tratamiento , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , AncianoRESUMEN
Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials.
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Exantema , Psoriasis , Enfermedades Cutáneas Vesiculoampollosas , Adulto , Humanos , Inhibidores de Interleucina , Psoriasis/tratamiento farmacológico , Interleucinas/genética , Interleucinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Aguda , Enfermedad CrónicaRESUMEN
BACKGROUND: Dupilumab is approved for moderate-severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real-world data because providers have limited practical experience with this recently approved therapy. OBJECTIVES: To describe the real-world effectiveness and safety in patients aged <12 years with moderate-severe AD currently receiving or previously having received dupilumab. METHODS: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off-label for dupilumab due to their age. RESULTS: Sixty three pediatric patients (37 males) with moderate-to-severe AD were included; the mean age was 6.4 years old (range: 2-11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI-75% and 71% (34/48) achieved EASI-90. EASI-75 and EASI-90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. CONCLUSIONS: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.
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Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Niño , Preescolar , Humanos , Masculino , Canadá , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Calidad de Vida , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Femenino , LactanteRESUMEN
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.
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BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.
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Artritis Psoriásica , Psoriasis , Humanos , Masculino , Estudios Prospectivos , Canadá/epidemiología , Psoriasis/epidemiología , Psoriasis/tratamiento farmacológico , Sistema de Registros , Índice de Severidad de la EnfermedadRESUMEN
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.