Publications by authors named "Wayne Gulliver"

87 Publications

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

JAMA Dermatol 2022 05;158(5):561-572

Centro Dermatologico "Dr. Ladislao de la Pascua," Mexico City, Mexico.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.

Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.

Design, Setting, And Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).

Main Outcomes And Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.

Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.

Conclusions And Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
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http://dx.doi.org/10.1001/jamadermatol.2022.0434DOI Listing
May 2022

Real-World Moderate-to-Severe Hidradenitis Suppurativa: Decrease in Disease Burden With Adalimumab.

J Cutan Med Surg 2022 Mar 24:12034754221088584. Epub 2022 Mar 24.

370608 AbbVie Corporation, Saint-Laurent, QC, Canada.

Background: Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited.

Objectives: To measure the impact of adalimumab on moderate-to-severe HS patients' health-related quality of life (HRQoL) and work productivity.

Methods: In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician's practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6-10, medium; ≥11, high).

Results: From baseline to weeks 24 and 52, all PRO overall scores improved significantly ( ≤ .0023). The number of patients reporting "good disease control" and "complete disease control" increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin "tenderness" and "itchiness" improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders.

Conclusion: At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients.
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http://dx.doi.org/10.1177/12034754221088584DOI Listing
March 2022

The Incidence of Cutaneous Malignant Melanoma in Eastern Newfoundland and Labrador, Canada, from 2007 to 2015.

Dermatology 2022 5;238(3):527-533. Epub 2021 Oct 5.

Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

Background: The incidence of cutaneous malignant melanoma continues to increase worldwide and in Canada. It is unclear whether the increase in incidence and clinical characteristic trends of cutaneous malignant melanoma are similar in the province of Newfoundland and Labrador.

Objective: The objective of this study is to examine the incidence and trends of cutaneous malignant melanoma in Eastern Newfoundland and Labrador.

Methods: Patients aged 18 years or older diagnosed with cutaneous malignant melanoma were identified from the Eastern Health Authority's Cancer Registry. The diagnosis was confirmed by a pathologist via histological subtype. Patients were excluded if the diagnosis was unspecified, a nonmelanoma skin cancer or if there was a recurrence in the same lesion location. In total 298 patients diagnosed with cutaneous malignant melanoma from 2007 to 2015 were included in the analysis.

Results: The total incidence increased from 4.1 to 15.6 cases/100,000 person-years, which represents a 283.0% increase from 2007 to 2015. The largest increases in incidence were seen in males and patients aged from 60 to 79 years. The most common lesion anatomical locations were the trunk in males and the lower extremity in females. The majority of cases had a Breslow thickness below 1.0 mm.

Conclusion: The incidence of cutaneous malignant melanoma in Eastern Newfoundland and Labrador is increasing at a faster rate than in any other region in Canada. Health care providers should work to be aware of the clinical trends and risk factors associated with this disease to facilitate early detection and prevent morbidity.
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http://dx.doi.org/10.1159/000519193DOI Listing
May 2022

Prevalence of Hidradenitis Suppurativa: A Systematic Review and Meta-regression Analysis.

JAMA Dermatol 2021 Aug;157(8):924-931

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany.

Importance: Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.

Objective: To estimate overall HS prevalence.

Data Sources: This review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil's disease). No language restriction was applied.

Study Selection: Original investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.

Data Extraction And Measures: Two reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.

Main Outcomes And Measures: Hidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).

Results: In 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).

Conclusions And Relevance: The findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
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http://dx.doi.org/10.1001/jamadermatol.2021.1677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156162PMC
August 2021

Investigation of prevalence of biologic use and discontinuation rates in moderate-to-severe psoriasis patients in Newfoundland and Labrador using real-world data.

Dermatol Ther 2021 05 22;34(3):e14944. Epub 2021 Mar 22.

Newlab Clinical Research Inc, St. John's, Newfoundland and Labrador, Canada.

Real-world data for psoriasis includes registries, and meta-analyses could help guide biologic therapy choice. The objective was to determine the prevalence and reason for discontinuation of biologic or PD4 inhibitor therapy in patients with moderate-to-severe psoriasis in Newfoundland and Labrador, Canada from 2001 to 2017. A retrospective cohort study was conducted on data collected between 2001 and 2017, to determine the type of biologic therapy or PD4 inhibitor, length of treatment, prevalence of and reason for discontinuation. As multiple patients have been on more than one therapy (ie, an average of 1.8), the 459 patients included in the registry have had a total of 913 exposures to biologic or PD4 inhibitors. The treatment mean time was 37 months (SD 39.95). A total of 180 patients remained on their first biologic of which 75% were male. The average number of biologics per patient was 1.99. The reasons for discontinuation were primary failure (28.5%), adverse events (26.4%), secondary failure (24.3%), patient choice (4.4%), other/unknown in (6.6%), drug withdrawal from market (6.8%), and drug coverage issues (3%). The most common reasons for discontinuation of biologics or PD4 inhibitors include primary failure, adverse events, and secondary failures. Males were more likely to remain on their first biologic.
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http://dx.doi.org/10.1111/dth.14944DOI Listing
May 2021

Comorbidity screening in hidradenitis suppurativa: Evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.

J Am Acad Dermatol 2022 05 23;86(5):1092-1101. Epub 2021 Jan 23.

Department of Dermatology, University of California, San Francisco, California.

Background: Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk.

Objective: To provide evidence-based screening recommendations for comorbidities linked to HS.

Methods: Systematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria.

Results: Screening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity.

Limitations: Screening recommendations represent one component of a comprehensive care strategy.

Conclusions: Dermatologists should support screening efforts to identify comorbid conditions in HS.
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http://dx.doi.org/10.1016/j.jaad.2021.01.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298595PMC
May 2022

What causes hidradenitis suppurativa ?-15 years after.

Exp Dermatol 2020 12;29(12):1154-1170

European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany.

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as "the only inflammatory skin disease than can be healed". This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.
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http://dx.doi.org/10.1111/exd.14214DOI Listing
December 2020

Moderate-to-severe plaque psoriasis patients treated with ixekizumab: early real-world outcomes and adverse events.

J Dermatolog Treat 2022 Feb 22;33(1):354-360. Epub 2020 Apr 22.

Eli Lilly and Company, Indianapolis, IN, USA.

Introduction: Data on real-world experiences for patients treated with ixekizumab is currently limited.

Objectives: Describe characteristics of ixekizumab-treated psoriasis patients and provide evidence of clinical outcomes using disease severity scores Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) in the real world.

Methods: Chart review was performed for adult patients treated with ixekizumab at a single Canadian dermatology clinic (February 2017-August 2018). The cohort was stratified into responders (patients who remained on ixekizumab) and non-responders (patients who discontinued ixekizumab). Subgroup analyses were performed for responders to assess clinical improvement stratified by previous biologic exposure.

Results: Thirty-eight patients were included (mean observational time 32 weeks). At baseline, mean PASI and BSA were 10.8 and 11.6%, respectively. Mean changes in PASI and BSA were -7.8 and -6.7%, respectively, at week 4. PASI 100 was achieved in 70% of patients. Significant differences in mean change of BSA were seen between bio-naïve and bio-experienced patients.

Conclusion: This analysis represents the first investigation of early clinical outcomes in a small cohort of Canadian patients treated with ixekizumab. Overall, complete and rapid skin clearance was observed. Future studies including more patients and longer follow-up time are crucial to confirm these findings.
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http://dx.doi.org/10.1080/09546634.2020.1755009DOI Listing
February 2022

Omalizumab Re-Treatment and Step-Up in Patients with Chronic Spontaneous Urticaria: OPTIMA Trial.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2372-2378.e5. Epub 2020 Apr 6.

Novartis Pharmaceuticals Canada Inc, Dorval, QC, Canada.

Background: Omalizumab shows greater clinical benefit with 300 mg dose than with the 150 mg dose.

Objective: To determine outcomes postwithdrawal, relapse, and re-treatment in omalizumab responders, and from stepping up to 300 mg after insufficient symptom control with 150 mg.

Methods: This was a prospective, randomized (3:4), open-label, noncomparator study (clinicaltrials.gov: NCT02161562). A total of 314 adult patients with chronic spontaneous urticaria and symptomatic on H-antihistamines were enrolled between August 1, 2014, and November 6, 2015. Patients received 150 mg/300 mg omalizumab, every 4 weeks for 24 weeks. Omalizumab 150 mg dose could be stepped up to 300 mg between week 8 and week 24, if the 7-day sum of the daily Urticaria Activity Score (UAS7) was more than 6. If patients relapsed after treatment withdrawal at week 24, they could be re-treated with the same dose on which omalizumab was started. Patients on 300 mg could extend treatment by 12 weeks if they did not achieve symptom control on 300 mg in the initial dosing phase. The primary end point was the proportion of well-controlled patients who relapsed postwithdrawal, and achieved symptom control at the end of re-treatment. Symptom control was assessed using UAS7 (UAS7 ≤ 6 = well controlled).

Results: Overall, 115 of 314 patients had adequate symptom control at week 24 (end of the initial dosing period) and 56 were re-treated after relapse postwithdrawal; 87.8% (95% CI, 78.6%-96.9%) regained symptomatic control (UAS7 ≤ 6). Most (141 of 178) patients initially treated with 150 mg required step-up to 300 mg, which resulted in a 9.5-point (95% CI, 7.6-11.3) improvement in UAS7 over the mean change observed initially on 150 mg.

Conclusions: Step-up to 300 mg helps a greater proportion of patients achieve symptom control, and re-treatment with omalizumab is as effective as initial therapy.
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http://dx.doi.org/10.1016/j.jaip.2020.03.022DOI Listing
May 2021

Weight Loss and Dietary Interventions for Hidradenitis Suppurativa: A Systematic Review.

J Cutan Med Surg 2020 Jan/Feb;24(1):64-72. Epub 2019 Sep 10.

210484 Division of Dermatology, University of Toronto, Canada.

Hidradenitis suppurativa (HS) is a common inflammatory disorder characterized by recurrent, painful, and malodorous abscesses and nodules predominantly in skin folds. HS is associated with substantial morbidity and poor quality of life. There are no curative therapies, and the only approved biologic drug has variable efficacy and requires high doses, making adjunct treatments crucial. An important risk factor for disease severity is obesity. Our primary objective was to conduct a systematic review examining weight loss and dietary interventions, in HS. Our secondary objective was to examine nutritional supplements in HS.A systematic literature search was conducted using Medline, EMBASE, and the Cochrane Database. We included all study types in adults (>18 years), with a minimum sample size of 5, examining the effects of any dietary or weight loss intervention on HS severity. Two authors screened = 1279 articles of which 9 met inclusion criteria. All included studies were observational and all interventions were associated with various measures of decreased HS severity. Patient-controlled weight loss and bariatric surgery were associated with HS regression, though a subset of patients with significant increase in panniculi experienced exacerbations and required excision of excess skin. Diets demonstrating benefit eliminated dairy and brewer's yeast. Nutritional supplements including zinc gluconate, vitamin D, and riboflavin had a suppressive, rather than curative, effect on HS lesions in single studies. Overall, the reviewed interventions show promise as potential adjunct treatments in a HS management plan. Prospective randomized controlled trials should validate these findings.
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http://dx.doi.org/10.1177/1203475419874412DOI Listing
November 2020

Checklist for the Systemic Treatment of Psoriasis Using Biologics: A Delphi Study.

J Cutan Med Surg 2019 May/Jun;23(3):282-288. Epub 2019 Mar 10.

2 Department of Medicine, University of Ottawa, Canada.

Background: Despite the complexity of psoriasis treatment using biologic therapy, there does not exist a standardized synoptic reporting form for the initiation of this population. The purpose of this study was to use a modified Delphi approach to develop a standard checklist for the standardized documentation of patients receiving systemic biologic therapy for psoriasis.

Methods: A modified Delphi survey was conducted over 3 rounds (February 2017 through January 2018). An expert panel generated a 51-item checklist that was proposed to participants. Items were rated on an anchored 1-7 Likert scale. Consensus was defined apriori as ≥ 70% agreement by respondents.

Results: A total of 58, 17, and 18 dermatologists participated in 3 consecutive Delphi rounds, respectively. Only half of the dermatologists surveyed reported using a checklist for the management of psoriasis. The final checklist comprised 19, 5, 6, and 9 items pertaining to patient history; physical exam and history of systemic therapy; vaccinations; and lab investigations and bloodwork, respectively.

Conclusions: Given the increasing availability and complexity of biologic agents for psoriasis treatment, there is a need to promote standardized documentation for this population. The Checklist for the Systemic Treatment of Psoriasis presents 38 items that should be considered when initiating patients with psoriasis on biologic therapy.
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http://dx.doi.org/10.1177/1203475419833605DOI Listing
December 2019

Treating to Target(s) With Interleukin-17 Inhibitors.

J Cutan Med Surg 2019 Mar/Apr;23(2_suppl):3S-34S. Epub 2019 Feb 11.

12 University of Alberta, Edmonton, AB, Canada.

Background:: The treat-to-target (T2T) strategy has become established in several medical specialties as a key guidance to optimal therapeutic decision making. T2T may be effective in the assessment of the biologic class of agents called interleukin (IL)-17 inhibitors, which are emerging as a safe and effective treatment option for autoimmune inflammatory conditions such as plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Objective:: The objective of this article is to use a T2T approach for the evaluation of the effectiveness and safety of IL-17 inhibitors in the management of patients with plaque psoriasis, PsA, and AS.

Methods:: Following a comprehensive literature search, a full-day meeting was convened to discuss and identify the T2T targets for psoriasis, PsA, and AS. Clinical trial evidence was presented for the approved IL-17 inhibitors-secukinumab, ixekizumab, and brodalumab-to assess whether these data meet T2T safety and efficacy targets.

Results:: All 3 approved agents were significantly superior to placebo and active controls in the achievement of T2T targets for psoriasis. Secukinumab and ixekizumab were likewise associated with significantly better outcomes than controls in the PsA targets, and secukinumab resulted in significant AS target improvements vs placebo. The IL-17 inhibitors were also associated with low rates of serious adverse events and exacerbations of common comorbid conditions.

Conclusion:: Phase III trial results support the T2T benefit and safety of IL-17 inhibitors according to their specific indications for the management of patients with plaque psoriasis, PsA, and AS.
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http://dx.doi.org/10.1177/1203475418824565DOI Listing
June 2019

The Association Between an Addictive Tendency Toward Food and Metabolic Characteristics in the General Newfoundland Population.

Front Endocrinol (Lausanne) 2018 9;9:661. Epub 2018 Nov 9.

Complex Disease Laboratory, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.

Our previous study of 29 obese food addiction (FA) patients found that FA is associated with lipid profiles and hormones which may be a factor in cardiovascular disease (CVD) and insulin resistance (IR). However, there is currently no data available regarding the relationship between FA symptoms and metabolic characteristics of CVD and IR in the general population. We designed this study to investigate the correlation between FA symptoms with lipid profiles and IR in men and women of the general Newfoundland population. 710 individuals (435 women and 275 men) recruited from the general Newfoundland population were used in analysis. FA symptoms were evaluated using the Yale Food Addiction Scale (YFAS). Glucose, insulin, HDL, LDL, total cholesterol and triglycerides levels were measured. IR was evaluated using the homeostatic model of assessment (HOMA). Participants were grouped by sex and menopausal status. Age, physical activity, calories and total % body fat were controlled. Partial correlation analysis revealed that in men, YFAS symptom counts were significantly correlated with HOMA-β ( = 0.196, = 0.021), triglycerides ( = 0.140, = 0.025) and inversely correlated with HDL ( = -0.133, = 0.033). After separating by menopausal status, pre-menopausal women exhibited no correlations and post-menopausal women had a significantcorrelation with triglycerides ( = 0.198, = 0.016). FA is significantly correlated with several markers of metabolic disturbance in men and to a lesser extent, post-menopausal women, in the general population. Further research is required to explain sex specific associations and elucidate any potentially causal mechanisms behind this correlation.
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http://dx.doi.org/10.3389/fendo.2018.00661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237829PMC
November 2018

Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents.

J Cutan Med Surg 2019 Mar/Apr;23(2):204-221. Epub 2018 Nov 21.

2 Division of Dermatology, University of Toronto, ON, Canada.

Introduction:: Many international guidelines for management of psoriasis exist and most have variations in grading evidence quality, strength of recommendations, and dosing. The objective of our review is to compare international guidelines published in the United Kingdom, Canada, Europe, and the United States for the management of moderate-to-severe plaque psoriasis.

Methods:: We conducted a literature review on systemic therapies and phototherapy for moderate-to-severe plaque psoriasis in adult patients. The British, Canadian, European, and American guidelines served as the key comparators in our review. To identify relevant supporting clinical trials not referenced in the guidelines, we conducted literature searches in PubMed and EMBASE. Two authors independently extracted data on indications, dosing, efficacy, evidence grade, and strength of clinical recommendation for each therapy.

Results:: Monoclonal antibodies directed toward tumour necrosis factor and interleukin (IL)-12/23 received the strongest recommendations for treatment of moderate-to-severe plaque psoriasis, supported by robust, high-quality randomized controlled trials (RCTs). Newer agents such as IL-17 and IL-23 inhibitors are not referenced in most guidelines. There are fewer RCTs for conventional therapies and few head-to-head comparisons with biologics, making it difficult to draw direct comparisons. Among older agents, methotrexate is most strongly recommended for long-term maintenance and cyclosporine is recommended for short-term control of flares.

Conclusion:: Physicians should individualize psoriasis-management strategies based on medication tolerance, efficacy, safety, patient comorbidities, availability of the medication, and patient preference.
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http://dx.doi.org/10.1177/1203475418814234DOI Listing
June 2019

An Investigation of Comorbid Disease and Health Service Utilization Among Patients With Moderate to Severe Psoriasis in Newfoundland and Labrador.

J Cutan Med Surg 2019 Jan/Feb;23(1):29-34. Epub 2018 Jul 24.

6 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Psoriasis is an inflammatory skin condition affecting 2% to 3% of the population and is associated with several comorbidities, including cardiovascular disease, depression, inflammatory bowel disease, metabolic syndrome, mood disorder, psoriatic arthritis, and weight gain. Psoriasis is treated with a number of topical and systemic therapies, including biologic drugs that directly target proinflammatory cytokines. This cross-sectional retrospective study investigated comorbid conditions reported in the Newfoundland and Labrador psoriasis population, outcomes associated with therapeutic treatment, and use of health care resources. Of the psoriasis comorbidities investigated, psoriatic arthritis was significantly associated with the use of biologic therapy while a failure to respond to biologics was associated with a higher incidence of cardiovascular disease. Patients responsive to biologic treatment had fewer hospital stays than patients treated with other therapies. Our results suggest that biologic therapies have a cardioprotective effect and reduce the number of hospital visits in patients whose symptoms are responsive to treatment.
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http://dx.doi.org/10.1177/1203475418791114DOI Listing
June 2019

Biologic Therapy Utilization in Patients With Moderate to Severe Psoriasis and Psoriatic Arthritis: An Observational Summary of Biologic Therapy Use in a Clinical Setting.

J Cutan Med Surg 2018 Nov/Dec;22(6):567-576. Epub 2018 Jun 28.

5 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Plaque psoriasis affects approximately 2% to 3% of the global population, with psoriatic arthritis observed in approximately 20% to 30% of these individuals. Upon advances in research pathophysiology and treatment over the past decade, biologic therapies have been used more to treat moderate to severe psoriasis. In Canada, reimbursement bodies have defined prior authorization criteria to determine patient eligibility for funding of biologic treatments in moderate to severe plaque psoriasis. Generally, patients will have been treated with conventional therapies such as topical steroids, phototherapy, or systemic treatments such as methotrexate and cyclosporine before starting a biologic therapy. In difficult cases or severe flares in otherwise controlled disease, practitioners may augment the regimen with one or more conventional treatments. The objective of this observational report was to identify treatment pathways for psoriasis and psoriatic arthritis patients in Canada by examining initial biologic treatment and subsequent treatment optimization patterns for informed reimbursement discussions and decisions. A retrospective chart review was conducted at Newlab Clinical Research using medical records of patients who received at least 1 of 4 biologic agents approved at that time of the survey in Canada for the treatment of plaque psoriasis (adalimumab, etanercept, infliximab, ustekinumab). The study population consisted of patients who had moderate to severe plaque psoriasis, diagnosed by a dermatologist, for at least 6 months before the study index date and who attended Newlab Clinical Research between 2008 and 2013. All current and previous agents prescribed for the treatment of psoriasis were captured. A total of 248 patients with psoriasis treated with biologics were identified, of whom 27 (10.9%) were also diagnosed with psoriatic arthritis. Prior to initiating treatment with a biologic, most patients (72.1%) were treated with (or contraindicated to) methotrexate/cyclosporine. Treatment was supplemented with topical agents (70.6%) and/or followed by a course of ultraviolet light phototherapy (51.6%). Only 2.4% of patients were treated with a biologic first. Of 248 patients treated with biologics, almost half (47.6%) needed add-on therapy, whereas 16.5% of patients had an increase in dose or dosing interval. Furthermore, 14.1% of patients added a topical agent, 10.5% a topical steroid, or 6.5% a course of phototherapy while continuing biologic therapies. Finally, 30.4% of patients switched to another biologic treatment. Adalimumab was the most common agent used as a second-line agent (37.2%), and patients who started on adalimumab mainly switched to ustekinumab as a second-line agent (73.9%). Infliximab was the agent least often used as second-line therapy.
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http://dx.doi.org/10.1177/1203475418786712DOI Listing
January 2019

Investigating the therapeutic potential of a probiotic in a clinical population with chronic hand dermatitis.

Clin Cosmet Investig Dermatol 2018 30;11:265-271. Epub 2018 May 30.

Research and Development, Bio-K Plus International Inc., Laval, QC, Canada.

Background: Hand dermatitis or hand eczema (HD) is one of the most common dermatologic conditions. Lesions, scaling, pruritus and pain are chronic and relapsing. Improved HD has been reported with the probiotic composed of CL1285, LBC80R and CLR2 (Bio-K+).

Purpose: Investigation of the therapeutic potential of this probiotic as the sole systemic treatment for adults with nonacute HD.

Subjects And Methods: A single-center study documented clinical ratings and patient-reported outcomes in adults with chronic HD. The probiotic was taken orally for 12 weeks, adjunctive to standard topical treatments and preventative measures.

Results: Most of the 30 subjects with mild to severe HD were compliant with the probiotic. Around 22 of the 30 subjects were able to complete the study, and of these subjects, an improvement was noted in 19. One required systemic therapy, and one subject was not able to tolerate the probiotic and therefore discontinued the study. 23% of the subjects achieved clear or almost clear hands by the end of 12 weeks. Pruritus, which was a common complaint at baseline, was improved with 59% of symptomatic patients within 2 weeks.

Conclusion: It is feasible and safe to administer Bio-K+ for HD. Clinicians saw an improvement in most subjects' hands, and cases of significant improvement in dermatitis were documented. Pruritus was the most rapidly relieved symptom, as reported by patients.
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http://dx.doi.org/10.2147/CCID.S164748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988048PMC
May 2018

Hidradenitis Suppurativa: A Novel Model of Care and an Integrative Strategy to Adopt an Orphan Disease.

J Cutan Med Surg 2018 Jan/Feb;22(1):71-77. Epub 2017 Oct 23.

1 Memorial University, St John's, Newfoundland, Canada.

Unnecessary investigations, inappropriate treatment, worsening disease, and frustration for both patients and health care professionals are the hallmarks of hidradenitis suppurativa (HS) management. In light of a new treatment algorithm and biologic therapies made available to patients, an HS model of care is outlined in this article. The recommendations and management strategy presented here have been developed to help address the currently unmet needs of this patient population. The patient-centred model of care and disease management strategies were developed through the guidance and recommendations of HS medical experts in Newfoundland and Labrador. This article lays the foundation for the resources and steps required to change the status of this orphan disease and firmly embed patients with HS within a coordinated and integrative system of care.
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http://dx.doi.org/10.1177/1203475417736290DOI Listing
August 2018

Secukinumab-Induced Psoriasiform Eruption.

JAMA Dermatol 2017 11;153(11):1194-1195

Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada.

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http://dx.doi.org/10.1001/jamadermatol.2017.2826DOI Listing
November 2017

Approach to the Management of Patients With Hidradenitis Suppurativa: A Consensus Document.

J Cutan Med Surg 2017 Nov/Dec;21(6):513-524. Epub 2017 Jun 22.

9 Centre de Recherche Dermatologique du Québec Metropolitain, Quebec, QC, Canada.

Background: Hidradenitis suppurativa (HS) is a painful, debilitating, and poorly understood condition, which is suboptimally diagnosed, managed, and treated. Evidence supporting various treatment modalities is sparse.

Objectives: To incorporate scientific evidence and expert opinions to develop useful guidance for the evaluation and management of patients with HS.

Methods: An expert panel of Canadian dermatologists and surgeons developed statements and recommendations based on available evidence and clinical experience. The statements and recommendations were subjected to analysis and refinement by the panel, and voting was conducted using a modified Delphi technique with a prespecified cutoff agreement of 75%.

Results: Ten specific statements and recommendations were accepted by the expert panel. These were grouped into 4 domains: diagnosis and assessment, treatment and management, comorbidities and a multidisciplinary approach, and education.

Conclusions: These statements and recommendations will serve to increase awareness of HS and provide a framework for decisions involving diagnosis and management. Evidence suggests that antibacterial and anti-tumour necrosis factor therapies are effective in the treatment of HS. This is supported by the clinical experience of the authors. Further clinical research and the establishment of multidisciplinary management teams will continue to advance management of HS in Canada.
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http://dx.doi.org/10.1177/1203475417716117DOI Listing
July 2018

Treating Psoriasis and Psoriatic Arthritis: Position Paper on Applying the Treat-to-target Concept to Canadian Daily Practice.

J Rheumatol 2017 04;44(4):519-534

From the University of Toronto, Toronto, Ontario; Université Laval, Quebec, Quebec; Queen's University, Kingston; University of Ottawa, Ottawa; Western University, London; Dermatrials Research, Inc., Hamilton, Ontario; Université de Montréal, Montreal; Université de Sherbrooke, Sherbrooke, Quebec; The Winnipeg Clinic, Winnipeg, Manitoba; University of Calgary, Calgary; University of Alberta, Edmonton, Alberta; University of British Columbia, Vancouver, British Columbia; Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

Objective: To develop preliminary treat-to-target (T2T) recommendations for psoriasis and psoriatic arthritis (PsA) for Canadian daily practice.

Methods: A task force composed of expert Canadian dermatologists and rheumatologists performed a needs assessment among Canadian clinicians treating these diseases as well as an extensive literature search on the outcome measures used in clinical trials and practice.

Results: Based on results from the needs assessment and literature search, the task force established 5 overarching principles and developed 8 preliminary T2T recommendations.

Conclusion: The proposed recommendations should improve management of psoriasis and PsA in Canadian daily practice. However, these recommendations must be further validated in a real-world observational study to ensure that their use leads to better longterm outcomes.
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http://dx.doi.org/10.3899/jrheum.161473DOI Listing
April 2017

High dietary selenium intake is associated with less insulin resistance in the Newfoundland population.

PLoS One 2017 5;12(4):e0174149. Epub 2017 Apr 5.

Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

As an essential nutrient, Selenium (Se) is involved in many metabolic activities including mimicking insulin function. Data on Se in various biological samples and insulin resistance are contradictory, moreover there is no large study available regarding the relationship of dietary Se intake with insulin resistance in the general population. To investigate the association between dietary Se intake and variation of insulin resistance in a large population based study, a total of 2420 subjects without diabetes from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study were assessed. Dietary Se intake was evaluated from the Willett Food Frequency questionnaire. Fasting blood samples were used for the measurement of glucose and insulin. Insulin resistance was determined with the homeostasis model assessment (HOMA-IR). Body composition was measured using dual energy X-ray absorptiometry. Analysis of covariance showed that high HOMA-IR groups in both males and females had the lowest dietary Se intake (μg/kg/day) (p < 0.01), being 18% and 11% lower than low HOMA-IR groups respectively. Insulin resistance decreased with the increase of dietary Se intake in females but not in males after controlling for age, total calorie intake, physical activity level, serum calcium, serum magnesium, and body fat percentage (p < 0.01). Partial correlation analysis showed that dietary Se intake was negatively correlated with HOMA-IR after adjusting for the Se confounding factors in subjects whose dietary Se intake was below 1.6 μg/kg/day (r = -0.121 for males and -0.153 for females, p < 0.05). However, the negative correlation was no longer significant when dietary Se intake was above 1.6 μg/kg/day. Our findings suggest that higher dietary Se intake is beneficially correlated with lower insulin resistance when total dietary Se intake was below 1.6 μg/kg/day. Above this cutoff, this beneficial effect disappears.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174149PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381811PMC
August 2017

Two novel candidate genes identified in adults from the Newfoundland population with addictive tendencies towards food.

Appetite 2017 08 20;115:71-79. Epub 2017 Jan 20.

Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address:

Food addiction (FA) is a distinguished clinical feature affecting about 5% adults of the general population in Canada. FA contributes to obesity, however, the underlying genes in FA are largely unknown. The aim of the current study was to search for FA candidate genes using an exome sequencing followed by a verification study using the most significantly associated identified genes. From a total of 752 adults, 24 subjects were selected including 8 obese with high and 8 obese with low/zero FA clinical symptom score (FAO, NFO), and 8 healthy controls with normal BMI and low/zero FA symptom score (Ctrl). Exome sequencing was completed in all three groups. The top 100 SNPs identified were categorized into 5 subgroups based on gene functions: addiction (Ad), psychological disorders, energy metabolism and obesity, and cancer, unknown function or with other diseases. In the verification study, the top 19 SNPs in the Addiction subgroup were genotyped in the entire 752 subjects using Sequenom iPLEX Gold genotyping technology. Comparison of NFO with Ctrl, and FAO with NFO, Ctrl and the combined group of NFO + Ctrl revealed 19 SNPs associated with Ad genes including, TIRAP, MMADHC, ERAP1, NTM, MYPN, GRID1, ITPR2, GPSM1, ZCCHC14, TNN, PPARD, CACNA1C, SIM1, and DRD2. Genetic association analysis was performed. The major allele A of rs2511521 located in DRD2 (OR = 3.1(95% CI 1.1-8.2)) and the minor allele T of rs625413 located in TIRAP (OR = 2.5(95% CI 1.1-5.8)) in NFO subjects significantly associated with increased risk of food addiction. Using a combination of exome sequencing method and a candidate gene association approach two new FA candidate genes are identified. Further study on the rest of the genes in the other four categories will be warranted.
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http://dx.doi.org/10.1016/j.appet.2017.01.004DOI Listing
August 2017

Review of Systemic Treatment Options for Adult Atopic Dermatitis.

J Cutan Med Surg 2017 Jan/Feb;21(1):31-39. Epub 2016 Sep 22.

10 Dermatrials Research Inc., Hamilton, ON, Canada.

Background: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease.

Objective: To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy.

Methods: A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search.

Results: Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence.

Conclusion: Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.
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http://dx.doi.org/10.1177/1203475416670364DOI Listing
October 2017

Psoriasis Patients Treated With Biologics and Methotrexate Have a Reduced Rate of Myocardial Infarction: A Collaborative Analysis Using International Cohorts.

J Cutan Med Surg 2016 Nov 8;20(6):550-554. Epub 2016 Jul 8.

Faculty of Medicine, Kuwait University, Kuwait.

Psoriasis is a chronic inflammatory skin condition characterised by the formation of red scaly plaques on the skin. It is an autoimmune disease cause by the dysregulation of cytokines controlling the inflammatory pathways, a mechanism likely contributing to various comorbidities observed in patients with psoriasis. Cardiovascular disease is one comorbidity observed more frequently in the psoriasis patient population. Biologic treatments specifically target the dysregulation of cytokines in the inflammation pathway and have shown to be an effective treatment for moderate to severe psoriasis where other systemic treatments have failed. More recently, biologics have been shown to reduce the incidence of myocardial infarction in patients with psoriasis compared to patients treated with topical agents. In the present study, 4 international psoriasis patient cohorts are combined and analyzed to examine the effect that biologic or methotrexate treatment has on reducing the incidence of myocardial infarction. Both methotrexate and biologic treatments were found to lower the incidence of myocardial infarction in moderate to severe psoriasis patient populations.
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http://dx.doi.org/10.1177/1203475416658004DOI Listing
November 2016

Do Biologics Protect Patients With Psoriasis From Myocardial Infarction? A Retrospective Cohort.

J Cutan Med Surg 2016 Nov 10;20(6):536-541. Epub 2016 May 10.

Division of Dermatology, University of Toronto, Toronto, ON, Canada.

Background: Psoriasis is a chronic immune-mediated inflammatory disorder that affects approximately 2% to 3% of the population, which translates to 17 million in North America and Europe and approximately 170 million people worldwide. Although psoriasis can occur at any age, most cases develop before age 40 years. Some larger studies have noted bimodal age at onset with the first peak occurring at approximately age 30 years and the second peak at around 55 to 60 years, but most patients have a younger age of onset (15-30 years). Psoriasis is associated with multiple comorbidities, decreased quality of life, and decreased longevity of life. Two recent systematic reviews and a meta-analysis concluded that psoriasis patients are at increased risk of major adverse cardiovascular events. Multiple studies confirm that many of the comorbidities found in patients with psoriasis are also important risk factors for cardiovascular disease, stroke, diabetes mellitus, hypertension, hyperlipidemia, obesity, and metabolic syndrome.

Methods: We conducted a retrospective cohort study using charts from a dermatology clinic combined with an administrative database of patients with moderate to severe psoriasis in Newfoundland and Labrador, Canada. We examined the role of clinical predictors (age of onset of psoriasis, age, sex, biologic use) in predicting incident myocardial infarction (MI).

Results: Logistic regression revealed that age of onset (odds ratio [OR], 8.85; P = .005), advancing age (OR, 1.07; P < .0001), and being male (OR, 3.64; P = .018) were significant risk factors for the development of MI. Neither biologic therapy nor duration of biologic therapy were statistically significant risk factors for the development of MI. Our study found that in patients with psoriasis treated with biologics, there was a nonsignificant trend in reduced MI by 78% (relative risk, 0.18; 95% confidence interval, 0.24-1.34; P = .056).

Conclusion: Our study demonstrated a trend toward decreased MI in patients with moderate to severe psoriasis on biologics. Patients with an early age of onset of psoriasis (<25 years) were nearly 9 times more likely to have an MI. Clinicians should consider appropriate cardiovascular risk reduction strategies in patients with psoriasis.
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http://dx.doi.org/10.1177/1203475416650430DOI Listing
November 2016
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