Toenail Onychomycosis with or without Diabetes in Canada: Patient Treatment Preferences and Health State Utilities.

Background: Toenail onychomycosis affects approximately 6.7% of Canadians. Symptoms include nail discolouration/disfiguration and pain; psychosocial impacts contribute to reduced health-related quality-of-life. Comorbid diabetes increases the risk of complications and exacerbates burden. Treatment may include topical therapy and/or oral agents. Purpose: To understand toenail onychomycosis treatment preferences, and to quantify the impact of toenail onychomycosis, with or without diabetes, on patient well-being. Methods: Adults living in Canada with self-reported, physician-diagnosed, toenail onychomycosis were recruited online. A discrete choice experiment was used to quantify treatment preferences. Scenarios were randomized; data were analyzed using conditional logit regression. Health state utilities were estimated using the Health Utilities Index Mark 3®. Results were stratified by diabetes status and toenail onychomycosis severity; the Wilcoxon Rank Sum test was used to assess between-group utility differences. Results: Three-hundred thirteen participants with toenail onychomycosis were included (161 had comorbid diabetes; 61.3%, severe onychomycosis). The mean age was 57.7 years; 55.9% were male. Treatment attributes with statistically significant impacts on patient preferences were efficacy (odds ratio [OR],1.04; 95% confidence interval [CI], 1.02-1.05 per 1% increased treatment success), administration method (one pill versus topical nail lacquer reference, 1.14; 1.04-1.26; topical solution applicator versus reference: 1.15; 1.03-1.29), severe adverse events (0.85; 0.80-0.90 per 1% increased risk), and risk of potential pharmacodynamic (0.80; 0.76-0.85) and alcohol (0.93; 0.88-0.98) interactions; preferences were more pronounced for efficacy and avoiding severe adverse events among toenail onychomycosis patients with comorbid diabetes. The mean (95% CI) utility value was 0.73 (0.70-0.75) overall, and statistically significantly lower (p=0.02) for toenail onychomycosis patients with diabetes (0.70; CI, 0.66-0.73) than those without (0.76; CI, 0.72-0.79). Conclusion: Among patients with toenail onychomycosis, the presence of diabetes was associated with differing treatment-related preferences. Utility values for patients with toenail onychomycosis represent a significant decline from full health that is exacerbated by comorbid diabetes.

Brodalumab for Plaque Psoriasis: A Canadian Real-World Experience at 2-Years Post-Launch.

BACKGROUND: There is limited real-life evidence with brodalumab in patients with plaque psoriasis in Canada. OBJECTIVES: To examine real-world effectiveness of brodalumab in Canadian routine care with a focus on clinician and patient-reported outcomes, as well as measuring continuation rates and persistency. METHODS: Retrospective analysis was conducted on data collected through the brodalumab patient support program (PSP) in Canada for patients initiating brodalumab between June 2018 (PSP launch)- June 2020 with a minimum of 16 weeks follow-up from first dose. Effectiveness was assessed by improvements in PASI, BSA and DLQI; continuation rates and persistency on therapy were reported. RESULTS: Overall, 864 patients (male, 59%; median age, 52 years) were included in the analysis. In a subset of patients with both baseline and follow-up scores, statistically significant improvements were observed: PASI improved from 13.9 to 1.8, BSA improved from 16.6% to 2.5% and DLQI improved from 16.2 to 2.9. Brodalumab demonstrated high continuation rates (89.9%), with similar rates in biologic-naïve and biologic-experienced patients (92.1% and 88.6%, respectively) and in patients who received secukinumab or ixekizumab as their most recent biologic therapy (89.0% and 86.2%, respectively). Persistence at 6, 12, and 18 months was 82.0%, 69.9%, and 63.4%, respectively. CONCLUSIONS: The effectiveness of brodalumab was demonstrated in this Canadian routine care study, with significant improvements in disease severity and patient-reported outcomes. High continuation rates were achieved; including in patients previously treated with IL-17A inhibitors. Future studies will provide further evidence of brodalumab's benefits for the management of plaque psoriasis in the real-world setting.

Short-term efficacy of latanoprostene bunod for the treatment of open-angle glaucoma and ocular hypertension: a systematic literature review and a network meta-analysis.

BACKGROUND/AIMS: To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP). METHODS: A systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated. RESULTS: A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%. CONCLUSION: LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Efficacy of Brodalumab for Moderate to Severe Plaque Psoriasis: A Canadian Network Meta-Analysis.

BACKGROUND: Several treatments for plaque psoriasis are available, but it remains challenging for physicians to make informed treatment decisions due to a lack of head-to-head trials. OBJECTIVES: This network meta-analysis (NMA) compares the efficacy of brodalumab to other biologic agents in Canada for moderate-to-severe plaque psoriasis. METHODS: A systematic literature review of randomized controlled trials (RCTs) published before October 2017 was conducted to populate the NMA. Comparators included etanercept, infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab, guselkumab, and placebo. The primary outcome was the psoriasis area and severity index (PASI) response at the end of induction phase. A random effects Bayesian multinomial likelihood and probit link model analyzed PASI 75, 90, and 100 responses. Inconsistency and heterogeneity were assessed. Sensitivity analyses were conducted to explore potential effect modifiers like baseline PASI score, age, and weight. RESULTS: A total of 43 RCTs were included. Brodalumab 210 mg had significantly better PASI response than etanercept, ustekinumab, adalimumab, secukinumab, and guselkumab and comparable responses to infliximab and ixekizumab. Relative risk of PASI 90 response for brodalumab varied from 2.84 (95% credible interval [CrI]: 2.35-3.52, P < .05) to 0.99 (95% CrI: 0.88-1.11, ns) compared to etanercept and ixekizumab. This was similar across PASI 75 responses, but a larger relative risk between brodalumab and all comparators except ixekizumab was observed for PASI 100. No significant heterogeneity or inconsistencies were identified. The results were consistent across sensitivity analyses, indicating robustness of the results. CONCLUSION: Brodalumab 210 mg has efficacy superior to most biologic agents for moderate-to-severe plaque psoriasis in Canada.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

Costs and Quality of Life in Diabetic Macular Edema: Canadian Burden of Diabetic Macular Edema Observational Study (C-REALITY).

Purpose. To characterize the economic and quality of life burden of diabetic macular edema (DME) in Canadian patients. Patients and Methods. 145 patients with DME were followed for 6 months with monthly telephone interviews and medical chart reviews at months 0, 3, and 6. Visual acuity in the worst-seeing eye was assessed at months 0 and 6. DME-related healthcare costs were determined over 6 months, and vision-related (National Eye Institute Visual Functioning Questionnaire) and generic (EQ-5D) quality of life was assessed at months 0, 3, and 6. Results. Mean age of patients was 63.7 years: 52% were male and 72% had bilateral DME. At baseline, visual acuity was categorized as normal/mild loss for 63.4% of patients, moderate loss for 10.4%, and severe loss/nearly blind for 26.2%. Mean 6-month DME-related costs/patient were as follows: all patients (n = 135), $2,092; normal/mild loss (n = 88), $1,776; moderate loss (n = 13), $1,845; and severe loss/nearly blind (n = 34), $3,007. Composite scores for vision-related quality of life declined with increasing visual acuity loss; generic quality of life scores were highest for moderate loss and lowest for severe loss/nearly blind. Conclusions. DME-related costs in the Canadian healthcare system are substantial. Costs increased and vision-related quality of life declined with increasing visual acuity severity.

Incidence and Characteristics of Patients with Visual Impairment due to Macular Edema Secondary to Retinal Vein Occlusion in a Representative Canadian Cohort.

Retinal vein occlusion (RVO) is an obstruction of the retinal venous system, and macular edema (ME) is a complication of RVO that can lead to blindness. The Canadian incidence of visual impairment (VI) due to ME secondary to RVO is unknown. This observational, retrospective study used records from the Southwestern Ontario database to observe the annual incidence, demographics, and comorbidity characteristics of patients with VI due to ME secondary to RVO. From 47,166 patients, 73 with RVO (>40 years old) were identified: 53 with branch retinal vein occlusion (BRVO), 20 with central retinal vein occlusion (CRVO). The annual incidence of VI (visual acuity <20/40 in Snellen equivalent) due to ME secondary to BRVO was (mean (95%CI)) 0.056% (0.011-0.072), and to CRVO was 0.021% (0.008-0.081). Furthermore, a greater proportion of RVO patients had hypertension (68% versus 14%) or dyslipidemia (16% versus 10%), when compared to a healthy control cohort of 76,077 subjects (P < 0.05). This study presents a description of the characteristics of patients with VI due to ME secondary to RVO in a real-world Canadian setting. The results demonstrate that BRVO was more frequent than CRVO, and that RVO in this patient population was associated with several vascular comorbidities.

The burden of illness in patients with moderate to severe chronic obstructive pulmonary disease in Canada.

INTRODUCTION: No recent Canadian studies with physician- and spirometry-confirmed diagnosis of chronic obstructive pulmonary disease (COPD) that assessed the burden of COPD have been published. OBJECTIVE: To assess the costs associated with maintenance therapy and treatment for acute exacerbations of COPD (AECOPD) over a one-year period. METHODS: Respirologists, internists and family practitioners from across Canada enrolled patients with an established diagnosis of moderate to severe COPD (Global initiative for chonic Obstructive Lung Disease stages 2 and 3) confirmed by postbronchodilator spirometry. Patient information and health care resources related to COPD maintenance and physician-documented AECOPD over the previous year were obtained by chart review and patient survey. RESULTS: A total of 285 patients (59.3% male; mean age 70.4 years; mean pack years smoked 45.6; mean duration of COPD 8.2 years; mean postbronchodilator forced expiratory volume in 1 s 58.0% predicted) were enrolled at 23 sites across Canada. The average annual COPD-related cost per patient was $4,147. Across all 285 patients, maintenance costs were $2,475 per patient, of which medications accounted for 71%. AECOPD treatment costs were $1,673 per patient, of which hospitalizations accounted for 82%. Ninety-eight patients (34%) experienced a total of 157 AECOPD. Treatment of these AECOPD included medications and outpatient care, 19 emergency room visits and 40 hospitalizations (mean length of stay 8.9 days). The mean cost per AECOPD was $3,036. DISCUSSION: The current costs associated with moderate and severe COPD are considerable and will increase in the future. Appropriate use of medications and strategies to prevent hospitalizations for AECOPD may reduce COPD-related costs because these were the major cost drivers.

Prevalence, Demographics, and Treatment Characteristics of Visual Impairment due to Diabetic Macular Edema in a Representative Canadian Cohort.

Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. However, there is limited understanding of the epidemiology of DME with visual impairment (VI) and treatment in patients with diabetes in Canada. This observational, retrospective study used records from the Southwestern Ontario database to observe the demographics, prevalence, and treatment characteristics of VI due to DME compared to a healthy population in a real-world Canadian setting. Data was compared between a cohort of 8,368 diabetic (type 1 or 2) patients, who were ≥18 years old and had a diagnosis of DME with VI (visual acuity <20/40 in Snellen equivalent), and 76,077 age- and gender-matched subjects representing a healthy population. Among diabetic patients, prevalence of DME was 15.7%, and prevalence of VI due to DME was 2.56%. Laser monotherapy was the most frequently used treatment. Public funding covered costs for 85% of persons with DME while 18% were paid for with private funds. This study provides insight into the demographics, prevalence, and treatment of VI due to DME in a representative Canadian cohort. This data can help to inform evaluation of current DME treatment patterns and of proposed new treatment on drug plan budgets in Canada.

Health-related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a naturalistic study.

BACKGROUND: Abdominal pain/discomfort, bloating, and constipation are gastrointestinal dysmotility and sensory symptoms associated with irritable bowel syndrome (IBS). No studies have followed patients with IBS symptoms for 1 year under conditions of routine clinical practice to assess prospectively the impact of treatments on health outcomes. OBJECTIVE: The objective of this ongoing, naturalistic study is to assess the long-term impact of IBS treatments on quality of life (QOL), work productivity, and resource utilization. This report describes the baseline characteristics and patterns of care of the patients enrolled in this study. METHODS: Patients with physician-diagnosed IBS symptoms were enrolled from 147 physician sites across Canada between May 4, 2004, and March 31, 2005. Clinical data were collected at baseline and at the end of the 12-month follow-up (patients were followed for 1 year between May 4, 2005, and March 31, 2006). Patient-reported outcomes were collected at baseline and at months 1, 2, 6, 9, and 12. Health-related QOL, health status, and work productivity were assessed with the IBS-QOL, a 5-item EuroQol descriptive system, and Work Productivity and Activity Impairment questionnaires, respectively. A resource utilization questionnaire elicited information on physician; visits, treatments, and procedures. Baseline data are reported here. RESULTS: Data were obtained from 1555 patients; 85.1% (1320/1552) were women. Patients had a mean (SD) age of 45.8 (15.0) years and mean (SD) duration of IBS symptoms of 11.4 (11.5) years. Self-reported bowel patterns were predominantly constipation (41.0%, 587/1433) and constipation alternating with diarrhea (39.4%, 564/1433); 60.3% (938/1555) of subjects used > or =3 IBS treatments in the previous 4 weeks. Approximately 50% of all patients reported distress "quite a bit or "extremely" for abdominal pain, gas, bloating, and constipation. The mean overall IBS-QOL score (0-100 scale, with 0 indicating poor QOL) was 66.3; food avoidance (51.8) and health worry (59.3) were the most serious concerns. Patients reported 5.6% work absenteeism, 31.4% presenteeism, and 34.6% overall work productivity loss, equivalent to 13.8 hours lost productivity per 40-hour workweek. CONCLUSIONS: The baseline data from this ongoing, prospective, naturalistic study are consistent with previous findings that suggested significant use of health care resources with concomitant low QOL and decreased work productivity in patients with IBS symptoms.

Burden of Atopic dermatitis in Canada.

BACKGROUND: Atopic dermatitis (AD) is relatively common worldwide; costs associated with the disease have been reported recently for various countries, but no estimates of costs in Canada are currently available. The objective of this study was to estimate the costs associated with AD in Canada, assessed from resource use determined for a Canadian setting. METHODS: Seventy-six patients in Ontario with AD were surveyed to determine information about severity of disease, healthcare practitioner visits, over-the-counter medication use, household expenses and absenteeism relating to their condition. Based on this information, costs were determined based on the Ontario billing schedule, estimated prescription use, reported out-of-pocket expenses and stated family income. Data about sleep disturbance and concern over topical corticosteroid use were also obtained. RESULTS: Patients reported an average of 3.6 publicly funded doctor visits per year for AD; 58% of these visits were to general practitioners and 28% to dermatologists. The annual per patient expenditure was estimated to be 282, 454 Canadian dollars and 1242 Canadian dollars for patients with mild, moderate and severe AD, respectively. The total cost of AD in Canada was estimated to be 1.4 billion Canadian dollars annually. More than half of the patients experienced sleep disturbances owing to their condition, and 71% reported having concerns about topical corticosteroid use. CONCLUSIONS: Although the cost per patient of AD in Canada is relatively low, owing to the prevalence of the disease, the total cost to society is large. Most of the cost is borne by patients and their employers, primarily owing to indirect costs associated with absenteeism.

Generic replacement of clozapine: a simple decision model from a Canadian perspective.

OBJECTIVE: Increased incidence of relapse has been differences in relapse incidence. The difference at reported upon switching patients with schizophrenia from brand name to generic clozapine. The cost of treating relapsed patients could offset the reduced drug acquisition cost associated with switching. A decision model was designed to predict the relapse incidence at which switching to generic clozapine is cost-neutral. RESEARCH DESIGN AND METHODS: A hypothetical cohort of 100 patients with schizophrenia stabilized on brand name clozapine was considered either to remain on the brand name product, or to switch to the generic version. Medication effectiveness data were taken from two reports following patients who underwent generic replacement of clozapine. Direct costs associated with each treatment were projected from a Canadian Ministry of Health perspective, considering drug acquisition and treatment of relapse. Unit costs were derived from published sources. MAIN OUTCOME MEASURES: Direct costs of the two treatment regimens were compared based on which switching to generic clozapine would result in no direct cost saving was determined. RESULTS: Switching a patient to generic clozapine would save 1241 Canadian dollars annually if the patient did not relapse, and would cost 9823 Canadian dollars if the patient relapsed. Assuming an 11% difference in relapse for patients taking brand name and generic clozapine, respectively, switching 100 patients to generic clozapine would save 24 Canadian dollars per patient. If the relapse difference for patients taking generic clozapine is 28%, the switch to the generic medication would cost 1857 Canadian dollars per patient. Switching patients from brand name clozapine to generic clozapine was predicted to be neutral to direct costs when the absolute difference in relapse incidence was 11.2%. CONCLUSIONS: Switching to a generic medication may not always reduce direct costs. Physicians, patients and third party payers should consider the potential consequences before instituting generic replacement of clozapine for economic reasons.

Cost effectiveness of Elidel in the management of patients with atopic dermatitis in Canada.

BACKGROUND: With increasing pressure on health care resources, it is necessary to demonstrate that new treatments are both effective and cost effective. OBJECTIVE: The purpose of this study was to assess the cost effectiveness of pimecrolimus (Elidel) compared to usual therapy in the treatment of both adults and children with atopic eczema in Canada. METHODS: Analysis was performed using a decision model which estimated the incremental cost per quality adjusted life year (QALY) gained from both a societal and health care perspective. RESULTS: For children, Elidel leads an incremental cost per QALY of 38,000 dollars from a societal perspective. For adults, the incremental cost per QALY was 35,000 dollars. CONCLUSION: Elidel will lead to an overall increase in costs but with an improvement in clinical outcomes. The cost effectiveness ratios for Elidel were consistently below 50,000 dollars per QALY gained. Given previous funding decisions in Canada, Elidel may be considered a cost-effective use of health care resources.