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BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.
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BACKGROUND: BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. OBJECTIVES: To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. METHODS: The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320â mg every 4 weeks (Q4W), bimekizumab 320â mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40â mg every 2 weeks to week 24 then bimekizumab 320â mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. RESULTS: Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24-104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. CONCLUSIONS: Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Humans , Adalimumab/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Psoriasis/drug therapy , Treatment Outcome , Double-Blind Method , Severity of Illness IndexABSTRACT
BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.
Subject(s)
Biological Products , Psoriasis , Humans , Etanercept/adverse effects , Injection Site Reaction/epidemiology , Injection Site Reaction/etiology , Biological Factors , Biological Products/adverse effects , Randomized Controlled Trials as TopicABSTRACT
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.
Subject(s)
Arthritis, Psoriatic , Psoriasis , Humans , Male , Prospective Studies , Canada/epidemiology , Psoriasis/epidemiology , Psoriasis/drug therapy , Registries , Severity of Illness IndexABSTRACT
Although topical drugs are the mainstay of treatment for patients with mild-to-moderate psoriasis, the developments observed in this field in the last two decades have been limited. The most commonly used drugs are still vitamin D analogues and corticosteroids, both with several limitations. The aryl hydrocarbon receptor (AhR) plays a role in the pathogenesis of psoriasis, and tapinarof, a novel, first-in-class, small molecule topical therapeutic AhR-modulating agent has been recently approved by the FDA for the topical treatment of plaque psoriasis in adults. Two large, 12-week, phase III trials, PSOARING 1 and 2, showed that 35.4%-40.2% of patients in the tapinarof 1% cream arm achieved the primary endpoint (Physician's Global Assessment [PGA] score of 0 or 1 and a decrease of ≥2-5 points at week 12) compared with 6.0%-6.3% for vehicle arm, respectively. The most common adverse effects were folliculitis, contact dermatitis, headache and pruritus. In the open label, 40-week, extension trial, PSOARING 3, the efficacy and safety results were similar, with 40.9% of patients achieving a PGA = 0 at least one time during the trial and 58.2% of patients with PGA≥2 achieved PGA = 0/1 at least once during the trial, without tachyphylaxis. There were no new safety signals, with most frequent adverse events being folliculitis, contact dermatitis, and upper respiratory tract infection. Tapinarof 1% cream has shown to be effective and to have a favorable safety profile in the treatment of psoriatic patients, representing an alternative to the current therapeutic options, increasing our armamentarium in the topical treatment of psoriasis.
Subject(s)
Dermatitis, Contact , Folliculitis , Psoriasis , Adult , Humans , Double-Blind Method , Psoriasis/diagnosis , Psoriasis/drug therapy , Psoriasis/pathology , Severity of Illness Index , Treatment OutcomeABSTRACT
Treat-to-target (T2T) recommendations for the use of systemic therapies (including biologics) in patients with moderate-to-severe plaque psoriasis have been published by a few groups of experts worldwide. However, there remains considerable variability in the choice of target severity measure and timing of milestones. To develop consensus recommendations for implementing T2T strategies for the management of moderate-to-severe plaque psoriasis using biologics. An expert group of Canadian dermatologists (the Committee) convened to develop a T2T consensus statement. They held a virtual meeting during which a preliminary set of criteria was created. These criteria were then reviewed, modified, and recirculated until unanimous agreement was achieved. The Committee agreed that defining treatment target is multidimensional and should reflect objective severity measures, as well as clinician and patient-reported outcomes. The Committee unanimously proposes a criterion-based system for determining the achievement of treatment target. The proposed T2T approach presented here provides a clinical framework for defining treatment success, measuring progress toward treatment success, recognizing when treatment modifications are warranted, and recommending treatment optimization strategies.
Subject(s)
Biological Products , Psoriasis , Biological Products/adverse effects , Canada , Consensus , Humans , Psoriasis/diagnosis , Psoriasis/drug therapy , Severity of Illness Index , Treatment OutcomeABSTRACT
This review examines the clinical, morphological, and systemic factors related to coronavirus disease 2019 (COVID-19) cutaneous manifestations. The EMBASE, Medline, and Pubmed Central databases were searched from February 1, 2020 until April 25, 2020, using the search words "(COVID-19 OR SARS-CoV-2 OR coronavirus-19) AND (skin OR cutaneous OR dermatologic)". Cutaneous manifestations of COVID-19 were included. The cutaneous manifestations can be classified into 2 types. Patients with inflammatory reactions consisted of morbilliform, varicella-like, urticarial eruptions, and vesiculobullous manifestations. These manifestations were mainly found on the trunk, limbs, and faces of patients and had mainly positive COVID-19 polymerase chain reaction findings (97.7%). Furthermore, there were 516 patients with acral vascular lesions: chilblains, livedo lesions, cutaneous small-vessel vasculitis, and other noninflammatory purpura. These were often nonpruritic (88%) and not seen in severe disease (88.7%). The cutaneous lesions have potential for early diagnosis of COVID-19 and prevention of disease transmission. The implications of COVID-19 in the field of dermatology continue to evolve as more clinical data becomes available.
Subject(s)
COVID-19/complications , Early Diagnosis , Pandemics , SARS-CoV-2 , Skin Diseases, Vascular/diagnosis , COVID-19/epidemiology , Humans , Skin Diseases, Vascular/etiologyABSTRACT
Psoriasis is an immune-mediated inflammatory skin disease that affects about 2% of the population and is associated with many comorbidities. Recent advances have demonstrated interleukin (IL)-17 signaling plays a crucial role in the pathogenesis of psoriasis. Bimekizumab is a novel monoclonal antibody treatment for psoriasis that uses a single binding site to inhibit IL-17A and IL-17F. Here we will discuss the safety and efficacy of bimekizumab in the treatment of moderate-to-severe plaque psoriasis.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Antibodies, Monoclonal/therapeutic use , Humans , Psoriasis/drug therapy , Treatment OutcomeABSTRACT
BACKGROUND: Secukinumab is an anti-IL-17A monoclonal antibody approved for the treatment of moderate-to-severe psoriasis in adult patients. Despite its favourable safety and efficacy profile in clinical trials, some patients in clinical practice fail to respond adequately to the approved maintenance regimen of 300 mg subcutaneous monthly. Some clinicians manage these patients by using off-label high-dose secukinumab regimens, which include shortening the dosing interval to 300 mg every 2 or 3 weeks instead of monthly, or increasing the monthly dose to 450 mg. OBJECTIVE: This study aims to investigate the safety and efficacy of high-dose secukinumab regimens for the treatment of psoriasis to inform real-world clinical practice. METHODS: We performed a retrospective chart review at 5 dermatology clinics for adult patients diagnosed with moderate-to-severe psoriasis treated with an off-label high-dose secukinumab regimen. Efficacy was measured using the Psoriasis Area and Severity Index or a Physician Global Assessment score of 0 or 1 after dose escalation. Adverse events were recorded to assess safety outcomes. RESULTS: Twenty-five patients were included in this case series, and 14 of them achieved efficacy from dose escalation with secukinumab based on our study endpoints. There was 1 case of the common cold and 1 upper respiratory tract infection reported after dose escalation. CONCLUSION: Our study provides evidence that dose escalation with secukinumab results in clinical benefit and is well tolerated among patients with moderate-to-severe psoriasis who failed to respond adequately to the approved regimen. This work necessitates larger studies to fully characterize the efficacy and long-term safety profile of secukinumab dose escalation.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Dermatologic Agents/administration & dosage , Psoriasis/drug therapy , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Dermatologic Agents/adverse effects , Female , Humans , Male , Middle Aged , Off-Label Use , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile. OBJECTIVE: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis. METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis. RESULTS: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative benefits were greater with secukinumab (all P < .05). LIMITATIONS: Analyses were post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients' lives.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Quality of Life , Ustekinumab/therapeutic use , Adult , Antibodies, Monoclonal, Humanized , Dermatologic Agents/adverse effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Severity of Illness Index , Time FactorsABSTRACT
BACKGROUND: Canadian dermatology curriculum was reviewed in 1983, 1987, 1996, and 2008. All these surveys highlighted the disproportionately low level of dermatology teaching in relation to the significant amount of skin disease seen by physicians. Since the official adoption and dissemination of the Canadian Professors of Dermatology (CPD) core curriculum and competencies, there has been no assessment of how these changes have influenced dermatology curriculum. OBJECTIVE: This survey gathered information on the current status of undergraduate dermatology education across Canadian medical schools. METHODS: A survey was sent electronically to all undergraduate dermatology directors at each of the 17 Canadian medical schools. RESULTS: Between 2008 and 2017, dermatology teaching has increased 25% to 25.6 ± 17.2 hours of teaching. However, 75% of this teaching is delivered in preclinical years. The number of faculty members, both dermatologists and nondermatologists, has also increased. A growing number of schools are now using electronic formats of teaching. Most schools (59%) are covering all the CPD core curriculum topics. CONCLUSION: Dermatology education is demonstrating positive trends with regards to teaching hours and faculty members. Nevertheless, a more even distribution of content so that students have increased clinical exposure should be achieved. Furthermore, an online atlas of resources would be helpful in standardising curriculum.
Subject(s)
Dermatology/education , Education, Medical/methods , Students, Medical/statistics & numerical data , Canada , HumansSubject(s)
Betacoronavirus/immunology , Biological Products/adverse effects , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Psoriasis/immunology , Withholding Treatment , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , Canada/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Susceptibility/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Psoriasis/complications , Psoriasis/drug therapy , Retrospective Studies , Risk Factors , SARS-CoV-2Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Medication Adherence , Pneumonia, Viral/epidemiology , Psoriasis/drug therapy , Thalidomide/analogs & derivatives , COVID-19 , Canada , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Thalidomide/therapeutic useABSTRACT
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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INTRODUCTION: New non-steroidal topical agents are needed for the treatment of psoriasis. Roflumilast cream 0.3% is a once daily phosphodiesterase-4 inhibitor that was recently approved by the FDA for the treatment of plaque psoriasis in adolescents and adults. It is indicated for use on all body surfaces including intertriginous areas. AREAS COVERED: In this review, we summarize the current knowledge about roflumilast cream for the treatment of psoriasis, highlighting its efficacy and safety profile from published clinical trials. Roflumilast's mechanism of action and pharmacokinetic profile are also discussed. EXPERT OPINION: Positive results were reported across trials with 48% of patients treated with roflumilast achieving an Investigator Global Assessment score of clear or almost clear at 8 weeks in phase III studies. Most adverse events were mild or moderate in severity and few application-site reactions were reported among participants. Unique advantages of the cream are its success in treating intertriginous areas and its ability to reduce symptoms of itch, results of which may significantly improve quality of life for patients. In the future, real-world data and active comparator trials with existing non-steroidal agents are needed to better understand roflumilast's place in the current treatment landscape.
Subject(s)
Psoriasis , Quality of Life , Adult , Adolescent , Humans , Psoriasis/drug therapy , Aminopyridines/therapeutic use , Aminopyridines/adverse effects , Benzamides/therapeutic use , Benzamides/adverse effects , Treatment Outcome , Severity of Illness IndexABSTRACT
BACKGROUND: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. OBJECTIVE: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. METHODS: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. CONCLUSION: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.
Subject(s)
Interleukin-17 , Psoriasis , Adult , Humans , Interleukin Inhibitors , Interleukin-23 , Psoriasis/drug therapy , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
INTRODUCTION: An estimated 2-4% of Western populations are thought to have psoriasis, with a regional incidence ranging from 0.09% to 11.43%. Variance in estimates is a result of differences in study populations, methodology, regional differences, and definitions of disease. Reliable prevalence estimates of plaque psoriasis are challenging to establish. Further, the distribution of psoriasis severity in the population is unknown. This study aims to establish the utility of expert elicitation (EE) as a method for estimating unknown parameters in dermatology by (1) estimating the prevalence of psoriasis in the adult population, and (2) estimating previously unknown disease severity distribution. METHODS: An expert panel of 11 Canadian dermatologists with demonstrated expertise in psoriasis was formed. A proof-of-concept EE exercise estimated psoriasis prevalence in the general population in Canada, followed by estimation of psoriasis disease severity distribution by body surface area (BSA). Expert estimates were consolidated using Bayesian methods to statistically model the data and represent uncertainty. RESULTS: The median prevalence of psoriasis in the adult population using the Bayesian estimate was 3.0% (95% credibility interval, 2.7-3.3%), compared with the estimated mean prevalence of 3.4% (95% confidence interval, 2.2-4.9%). By EE, the estimated cumulative distribution of disease severity assessed by BSA suggests that approximately 50% of patients have a BSA of < 3% and 78% of patients have a BSA of < 10%, with only 2% having a BSA of > 50%. CONCLUSION: The EE approach resulted in prevalence estimates that had a narrow distribution and were consistent with published literature, supporting its value in dermatology as a complementary method to help guide decision-making in areas where evidence is scarce or uncertain.
Psoriasis is a common skin disease that affects 24% of the population. Prevalence estimates vary depending on factors such as study type and population studied. The distribution of disease severity (what proportion of patients have mild, moderate, or severe psoriasis) is not known. In this study, 11 dermatologists with expertise in psoriasis used an approach called expert elicitation to make educated guesses about prevalence and disease severity distribution in the real world. Using a statistical approach called Bayesian estimation, experts can represent the level of certainty in what they know and do not know and make inferences or assumptions about a population. Bayesian estimates are not based on the amount of data; rather, each datum contributes to a statistically meaningful result. The median prevalence of psoriasis in the adult population using the Bayesian estimate was 3.0%, which is in the expected range based on prior literature and supports the use of this expert elicitation method. This study provides the first expert estimate of disease severity distribution in the population assessed by body surface area affected by psoriasis. Approximately 50% of psoriasis patients have mild disease (< 3% body surface area involved) and 78% of patients have mild or moderate disease (< 10% body surface area involved). Only 2% of patients have more than 50% body surface area involved. This expert elicitation approach can be used to help guide decision-making in areas of dermatology where evidence is lacking or uncertain.
ABSTRACT
BACKGROUND: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. METHODS: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. RESULTS: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418-0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257-1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. CONCLUSION: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower.
Subject(s)
Biological Products/therapeutic use , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Adult , Aged , Biological Products/pharmacology , Dermatologic Agents/pharmacology , Female , Follow-Up Studies , Humans , Interleukin-12/antagonists & inhibitors , Interleukin-12/immunology , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Interleukin-23/antagonists & inhibitors , Interleukin-23/immunology , Male , Middle Aged , Psoriasis/immunology , Remission Induction/methods , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The pandemic known as coronavirus disease-19 (COVID-19) has quickly spread worldwide, with a significant impact on lives all over the world. The complexity related to the new coronavirus and the clinical syndrome it causes is not yet fully understood. The impact of COVID-19 on patients with psoriasis under biologic agents is continuously being observed in this rapidly changing pandemic. A case-by-case evaluation must be made by dermatologists, and the final decision should be discussed and decided by both the patient and the specialist. Observations reveal that immunosuppressive therapy may have a role in the treatment of this virus, placing emphasis on the scenario of safety through maintenance of therapy with biologic agents, especially when there are no signs or symptoms related to the infection or contact with an infected patient.