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.

Hearing improvement among children with cholesteatoma who underwent canal wall up and canal wall down surgical management.

Objectives: The most frequently used surgical methods for treating cholesteatoma include canal wall up and canal wall down procedures. The objective of the study was to compare the hearing improvement among children with cholesteatoma who underwent canal wall up and canal wall down surgical management. Methods: The cross-sectional analytical study design was used. The study was conducted at the ENT Department of Nishtar Medical University & Hospital Multan from 15th June to 15th Nov 2020.. Forty six patients with cholesteatoma were enrolled in the study after taking informed consent. Inclusion and exclusion criteria were followed. The participants were categorized into two groups. Group-A was treated with canal wall-up surgery while Group-B was treated with canal wall down Mastoidectomy. A 12-month post-operative follow-up and the audiometry assessment were compared with pre-surgical values. Additionally, a COMOT-15 survey was administered to analyze self-perceived hearing functions. The Chi-square test was used for comparative analysis of the surgical outcome and hearing improvement among the two groups. P-value (p value<0.05) was considered statistically significant. Results: Forty six patients were included in the study with 23 participants in each group. Among 46, 26 were male and 20 were female. The pre and post-operative mean Pure-tone average values were significantly different in (Group-A) who underwent canal wall up Mastoidectomy (p<0.05) than in Group-B, who underwent canal wall down Mastoidectomy. Similarly, hearing sub-section responses of the COMOT-15 survey favored the Canal wall technique. However, the survey showed no significant differences in the mental health status of the two groups (p<0.05). Conclusion: Our data collected after a one-year follow-up of patients suggests canal wall up as a preferred technique for hearing improvement than canal wall down technique.

Real-World Treatment Patterns and Survival Among Patients with Stage I-III, Non-Squamous, Non-Small Cell Lung Cancer Receiving Surgery as Primary Treatment.

INTRODUCTION: Approximately half of patients with non-small cell lung cancer (NSCLC) present with early-stage disease at diagnosis. Real-world outcomes data are limited for this population but are of interest given recent and impending results from trials evaluating epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapies in neoadjuvant, adjuvant, and perioperative settings. METHODS: A retrospective, longitudinal, population-level study was conducted in patients diagnosed with resected stage I-III non-squamous NSCLC in Ontario, Canada, between April 2010 and March 2019. Study outcomes included patient characteristics and median overall survival (mOS), with stratification by disease stage and treatment exposure. Patients receiving EGFR-TKIs (assumed EGFR mutation-positive by proxy) were a key population of interest. RESULTS: Among 8255 cases, 4881 had stage I, 2124 had stage II, and 1250 had stage III NSCLC at diagnosis. The mean patient age was 68 years; 53.5% were female. In the overall cohort, 19.6% received adjuvant chemotherapy. Receipt of adjuvant chemotherapy was associated with significantly longer mOS than not receiving such therapy: stage II (7.6 [95% confidence interval: 6.5-8.5] vs. 4.4 [4.0-4.9] years) or stage III (4.4 [3.6-5.1] vs. 2.7 [2.3-3.3] years), both p < 0.0001. Patients receiving treatment (EGFR-TKIs and chemotherapy) were assumed to have experienced disease recurrence/relapse; mOS was longer among those receiving an EGFR-TKI than among those receiving chemotherapy (2.3 [1.8-3.0] vs. 1.1 [1.0-1.3] years). CONCLUSION: In Ontario, between 2010 and 2019, uptake of adjuvant therapy was low among patients with resected NSCLC, despite such therapy being associated with improved survival. Patients assumed to have recurred/relapsed had markedly reduced mOS, regardless of subsequent therapy, compared with those who did not relapse/recur. Novel peri-adjuvant treatment options are needed to enhance outcomes after lung resection.

A real-world retrospective analysis of the management of metastatic castrate-resistant prostate cancer in Ontario, Canada from 2010 - 2018.

PURPOSE: We sought to quantify mCRPC patient treatment patterns and survival across multiple lines of therapy after prior androgen-receptor-axis-targeted therapy (ARAT) failure. METHODS: Individuals diagnosed with prostate cancer between 2010 and 2018 were identified in the Ontario Cancer Registry (OCR). An algorithm was created to identify patients with mCRPC that was aligned to Prostate Cancer Clinical Trials Working Group 3 criteria (PCWG3) and validated with Canadian clinical experts. In the mCRPC setting, treatment patterns were assessed by line of therapy, and survival was calculated from treatment initiation until death or lost to follow-up. RESULTS: 64,484 men were diagnosed withprostate cancer in Ontario between 2010 and 2018with 5,588 men assessed to have mCRPC and 2,970 (53%) of those received first-line systemic treatment. Across the first-, second- and third-line of therapy, ARATs (abiraterone and enzalutamide) were the most used therapies. Survival for mCRPC patients treated with ARATs in first-, second- and third-line were 13.0 (95% CI, 11.6 - 14.5), 11.5 (95% CI, 10.1 - 13.4) and 8.9 (95% CI, 7.4 - 10.2) months, respectively. Survival for mCRPC patients treated with taxanes in first, second- and third-line were 16.7 (95% CI, 14.8 - 18.0), 11.3 (95% CI, 10.1 - 12.5) and 7.8 (95% CI, 6.5 - 10.6) months, respectively. No statistical difference in overall survival was found between taxanes and ARATs. CONCLUSION: In this analysis of a large retrospective cohort of Canadian men with mCRPC, we found that survival in patients treated with ARATs and taxanes was fairly similar across all lines of therapy. Importantly, this trend was maintained in ARAT-exposed patients, where sequential ARAT and taxanes offered similar survival. These data may help inform optimal sequencing of therapies in mCRPC.

Systemic Sclerosis and Associated Interstitial Lung Disease in Ontario, Canada: An Examination of Prevalence and Survival Over 10 Years.

OBJECTIVE: Systemic sclerosis (SSc) is a rare autoimmune disease. Pulmonary complications of SSc are some of the leading causes of morbidity and mortality. The objective of this study was to determine prevalence and survival estimates of SSc and SSc with interstitial lung disease (SSc-ILD) in the Canadian province of Ontario using administrative data over 10 years. METHODS: Using International Classification of Diseases, 10th revision codes adapted for Canada (ICD-10-CA), adult patients diagnosed with SSc and SSc-ILD between April 1, 2008, and March 31, 2018, were identified from the National Ambulatory Care Reporting System and the Discharge Abstract Database administrative databases. SSc was identified first, and ILD was included if presence occurred after SSc diagnosis. Prevalence estimates were determined for both SSc and SSc-ILD. For survival rates, Kaplan-Meier survival curves were generated. RESULTS: At the start of the 2017/18 fiscal year (final year of the cohort), there were 2114 prevalent SSc cases for a cumulative prevalence of 19.1 per 100,000 persons, as well as 257 prevalent cases of SSc-ILD that generated a prevalence of 2.3 cases per 100,000 persons. Mean ages were 57 and 58 years with 84% and 80% females for patients with SSc and SSc-ILD, respectively. One-, 5-, and 10-year survival rates were 85.0%, 64.5%, and 44.9% for the SSc group and 77.1%, 44.4%, and 22.0% for the SSc-ILD group, respectively. CONCLUSION: To our knowledge, this study provides the first population-based estimates of SSc and SSc-ILD in Canada for prevalence and survival. Results confirm that the prevalence estimates of SSc-ILD fall within the Canadian threshold for rare disease. It also demonstrates the poor survival in SSc, especially when ILD is also present.

Real-World Treatment Patterns, Survival, and Costs for Ovarian Cancer in Canada: A Retrospective Cohort Study Using Provincial Administrative Data.

Background: In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. Objective: There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. Methods: Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. Results: Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD $124 202 in stage IV. Discussion: The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. Conclusion: Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival.

Examining Treatment Patterns and Real-World Outcomes in Chronic Lymphocytic Leukemia Using Administrative Data in Ontario.

Information on the real-world experience of Canadians diagnosed with chronic lymphocytic leukemia (CLL) is limited. This study was conducted to report treatment patterns and outcomes of CLL using Ontario administrative data. A retrospective cohort study was conducted in patients diagnosed with CLL between 1 January 2010 and 31 December 2017 identified in the Ontario Cancer Registry (OCR). Data were accessed using the Institute of Clinical Evaluative Sciences (ICES), which collects various population-level health information. In the Ontario Cancer Registry, 2887 CLL patients receiving treatment and diagnosed between 2010-2017 were identified. Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy was most frequently used as a first line, but use declined since ibrutinib and obinutuzumab combinations were funded in 2015. In patients treated with frontline FCR, survival at year one was 89% pre-2015 and 96% post-2015; at year four, survival was 73% and 87%, respectively. Survival in patients treated with frontline chlorambucil was 76% pre-2015 and 75% post-2015 in year 1, and 45% and 56% in year 3. Our analysis shows that, as the treatment landscape for CLL has shifted, use of newer and novel agents as a first line or earlier in the relapsed/refractory setting has resulted in improved survival outcomes.

Cost and Resource Use of Pemphigus and Pemphigoid Disorders Pre- and Post-Rituximab.

BACKGROUND: Rituximab (RTX) is increasingly used for the treatment of pemphigus and pemphigoid disorders. The high cost of RTX frequently limits its use and access. OBJECTIVE: To determine the health system resources and costs associated with RTX treatment of pemphigus and pemphigoid. METHODS: Health system resources and costs attributed to a convenience sample of 89 patients with either pemphigus or pemphigoid were identified, quantified, and valued 6 months prior to and following RTX initiation between May 2006 and August 2012. Overall cohort costs and costs per patient were calculated (2013 Can$). RESULTS: The overall cohort cost for 6 months pre-RTX was $3.8 million and for 6 months post-RTX was $2.6 million. The average cost per patient decreased from $42,231 to $29,423 (30.3% decrease). The main cost driver was intravenous immunoglobulin. CONCLUSIONS: Our findings suggest that RTX is effective in reducing health system resources and the costs associated with the treatment of pemphigus and pemphigoid.

Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of NCIC CTG LY.12.

BACKGROUND: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. METHODS: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. RESULTS: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. CONCLUSIONS: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.