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.

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.