OBJECTIVE:We assessed sex differences in hospitalization rates among people with HIV (PWH) and people without HIV (PWoH) in British Columbia (BC). METHODS:PWH and a 10% random sample of PWoH in BC aged ≥19 were followed from 04/01/2002 to 03/31/2020, using linked administrative Comparative Outcomes and Service Utilization Trends (COAST) study data. Hospitalizations were categorized by discharge diagnosis, using broad International Classification of Diseases-classes. Using Poisson regression, we modelled the association between sex, HIV-status, their interaction, and hospitalization rates adjusting for confounders. RESULTS:Among 12,635 PWH (17.81% females) and 548,992 PWoH (49.34% females), age-adjusted hospitalization rates per 100 person-years were highest among females with HIV [incidence rate (IR) 34.25], followed by males with HIV (IR 21.49), females (IR 7.10), and males (IR 7.06) without HIV. Hospitalization rates for all causes declined from 2002-2022 across all subgroups but remained consistently higher among females with HIV, except for circulatory diseases and neoplasms. Adjusted for socio-structural factors, being male [rate ratio (RR) 1.92] or female with HIV (RR 2.66) was significantly associated with a higher hospitalization rate compared to males without HIV. Among PWH, female sex remained significantly associated with a higher hospitalization rate, after adjusting for HIV- and disease-related factors. CONCLUSIONS:We found a higher hospitalization rate among PWH than PWoH in BC, with the highest rate among females with HIV. This could partially be explained by socio-structural factors. Addressing these disparities and improving our understanding of the underlying mechanisms is critical to enhance health outcomes for women with HIV.

OBJECTIVE:Uptake of biosimilars has been suboptimal in North America. This study was undertaken to quantify the impact of various policy interventions (namely, new start and switching policies) on uptake and spending on biosimilar infliximab and etanercept in British Columbia (BC), Canada.METHODS:We used administrative claims data to identify BC residents ≥18 years of age with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and/or plaque psoriasis who qualified for public drug coverage from January 2013 to November 2020. Using interrupted time series analysis, we studied the change in proportion spent on and prescriptions dispensed of biosimilar infliximab and etanercept out of the total amount per agent after new start and biosimilar switching policies were implemented.RESULTS:Our study included 208,984 individuals living with rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, and/or psoriatic arthritis, corresponding to 5,884 patients taking infliximab and etanercept. After the new start policy, we detected a small gradual increase in the proportion of dispensed biosimilar etanercept prescriptions of 0.65% per month (95% confidence interval [95% CI] 0.44, 0.85). The trend related to the proportion of total spending on biosimilar etanercept also increased (0.51% [95% CI 0.28, 0.73]). After the switching policy, there was a sustained increase in the proportion of dispensed biosimilar etanercept and infliximab prescriptions of 76.98% (95% CI 75.56, 78.41) and 58.43% (95% CI 52.11, 64.75), respectively. Similarly, there was a persistent increase in monthly spending on biosimilar etanercept and infliximab of 78.22% (95% CI 76.65, 79.79) and 71.23% (95% CI 66.82, 75.65), respectively.CONCLUSION:We found that mandatory switching policies were much more effective than new starting policies for increasing the use of biosimilar medications.

Background The uptake of biosimilars has been suboptimal in North America. In response, in 2019, British Columbia (BC) became the first jurisdiction in North America to require patients with inflammatory arthritis to switch to a biosimilar version of infliximab and etanercept to maintain public coverage through the ‘Biosimilars Initiative’ policy. In 2021 this policy was extended to include adalimumab. The Biosimilars Initiative extended a previous policy which required people starting a biologic to use a biosimilar. Large commercial insurers which provide supplementary drug coverage also introduced biosimilars policies in line with the BC provincial government. Under both biosimilar switching policies, exceptional coverage to reference products was allowed if medically needed. Objectives To quantify the impact of the Biosimilars Initiative and the initial policy requiring new initiators to a biologic to use a biosimilar on uptake and spending on biosimilar infliximab, etanercept, and adalimumab in British Columbia (BC). Methods Administrative claims data in BC from January 2013 through March2023 were analyzed using interrupted time series analysis, a quasi-experimental study design commonly used to evaluate policy changes. Two policy interventions were evaluated: (1) new starts, whereby individuals initiating infliximab, etanercept, or adalimumab for the first time were required to start the biosimilar (implemented between Feb 2016 and July 2017), and (2) mandatory switching, which required those already receiving infliximab or etanercept (implemented between May and Nov 2019), or adalimumab (implemented between April and October 2012) to switch to the biosimilar version in order to maintain coverage. A segmented linear regression was used to model the level and trend change in biosimilar etanercept and infliximab utilization and spending before and after the two policy interventions. Results We identified 208,984 BC residents ≥18 years who qualified for public drug coverage, were treated with etanercept or infliximab, and were eligible for analysis between January 2013 and November 2020. After the new start policy, we detected a small gradual increase in the proportion of biosimilar etanercept prescriptions dispensed of 0.65% (95%CI 0.44, 0.85) per month. The monthly trend related to the proportion of total spending on biosimilar etanercept also increased (0.51, 95%CI 0.28, 0.73). After the mandatory switching policy (the Biosimilars Initiative), there was a sustained increase in the proportion of biosimilar etanercept and infliximab prescriptions dispensed of 76.98% (95%CI 75.56, 78.41) and 58.43% (95%CI 52.11, 64.75), respectively. Similarly, there was a persistent increase in spending on biosimilar etanercept and infliximab of 78.22% (95%CI 76.65, 79.79) and 71.23% (95%CI 66.82, 75.65), respectively. Similar results were seen for adalimumab which was switched later. Conclusion Our study found new start policies resulted in small, gradual increases in biosimilar utilization. However, the mandatory switch policy, the Biosimilars Initiative, resulted in a marked immediate and sustained impact on uptake. Further analysis will examine changes in other health utilization, and long-term impact on prescribing patterns. These findings may be particularly relevant to areas with a more concentrated insurance system where mandatory switching policies could lead to greater savings. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Overall proportion of prescriptions dispensed that were biosimilar etanercept and infliximab

Anticancer biosimilar use is rising but significant potential savings remain unrealized @alison_mcclean @ChrisLuPhD

E891 Les agents biologiques représentent un segment important des dépenses en médicaments au Canada : alors qu’ils ne constituaient que 1,5 % du volume des ordonnances, les agents biologiques ont généré 27,3 % des dépenses en 20181. En date de 2018, le prix des agents biologiques au Canada, y compris les dépenses par personne, n’arrivait qu’au second rang après les États-Unis parmi les pays de l’Organisation de coopération et de développement économiques (OCDE)2. Par exemple, le Canada a consacré plus d’argent aux anti-TNF (facteur de nécrose tumorale), une classe d’agents biologiques, qu’à tout autre médicament remboursé par les régimes publics3. Au cours des 10 dernières années, le Canada a triplé ses dépenses en agents biologiques et le phénomène ne semble pas en voie de s’estomper4. Avec plus de 1000 agents biologiques commercialisés au Canada et le fait qu’ils sont utilisés dans la plupart des spécialités cliniques, il devient absolument nécessaire de chercher à en maîtriser les coûts5. Les biosimilaires, des agents dotés d’une efficacité et d’une innocuité semblables à celles des médicaments d’origine, constituent une importante piste de solution1,4,6,7. Or, pour l’instant, seulement 31 biosimilaires sont approuvés au Canada, soit moins de la moitié par rapport au nombre disponible sur le territoire de l’Union européenne, et l’utilisation des biosimilaires au Canada est relativement faible5,8. Nous avons voulu faire le point sur les politiques actuelles relatives aux biosimilaires et leur utilisation au Canada à l’aide de 3 cas éloquents : l’infliximab, l’étanercept et l’insuline glargine. Nous abordons brièvement l’interchangeabilité et l’extrapolation des indications avant de formuler des suggestions pour améliorer le marché en harmonisant les politiques relatives aux biosimilaires, en favorisant l’enseignement aux patients et aux prescripteurs et en suscitant l’implication des fabricants.

BackgroundAdvances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART).ObjectiveTo examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada.MethodsData were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly.ResultsAll CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016.ConclusionsConcordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

KEY POINTS Biologics represent a large segment of drug spending in Canada: although they constituted just 1.5% of prescription volumes, biologics accounted for 27.3% of expenditures in 2018.[1][1] As of 2018, the price of biologics in Canada, including spending per capita, was second only to that in

Background: Socioeconomic status has been associated with higher viral loads and lower CD4 cell counts among people living with HIV. The objective of this study was to evaluate the relation between neighbourhood-level material deprivation and immunologic and virologic response to combination antiretroviral therapy (ART) among people living with HIV in Canada. Methods: The Canadian Observational Cohort (CANOC) is a longitudinal cohort of people living with HIV, containing data from 2000–2016 from 5 Canadian provinces. We defined response to combination ART as positive if the CD4 cell count increased by 50 cells/mm3 (0.05 cells × 109/L) or more (CD4+) and viral load decreased to 50 copies/mL or less (VL+) within 6 months of treatment initiation. We further categorized response to therapy as concordant positive (CD4+/VL+), concordant negative (CD4−/VL−) or discordant (CD4+/VL− or CD4−/VL+). We used adjusted multinomial logistic regression to quantify the relation between neighbourhood-level material deprivation and immunologic and virologic response. Results: This study included 8274 people living with HIV, of which 1754 (21.2%) lived in the most materially deprived neighbourhoods. Most individuals (62.2%) showed a concordant positive response to combination ART. After adjustment, living in the most materially deprived neighbourhoods was associated with a CD4−/VL+ discordant response (adjusted odds ratio [OR] 1.31, 95% confidence interval [CI] 1.06–1.62) and a concordant negative response (adjusted OR 1.45, 95% CI 1.13–1.86), using a concordant positive response as the reference. No other deprivation quartile was independently associated with a particular response. Interpretation: People living with HIV from the most materially deprived neighbourhoods had increased odds of poor immunologic or virologic response to combination ART. These results motivate further study of the specific socioeconomic factors that potentially affect response to combination ART among people living with HIV in Canada.

The use of data intensive health research has allowed for greater understandings of population health. When conducting data intensive health research, engaging and involving the community is essential for conducting meaningful research that is responsive to the public’s needs. Particularly, when engaging Indigenous communities in research, there is a need to understand historical and ongoing impacts of colonialism and recognize the strengths in Indigenous Peoples’ knowledges and experiences while supporting Indigenous leadership and self-determination in research. This article describes the approach our research team/organization used to engage and involve Indigenous people living with HIV in three research projects using large, linked datasets and looking at HIV outcomes of Indigenous populations in Canada. The foundation of these projects was simultaneously: 1) supporting Indigenous people living with HIV to be involved as research team members, 2) developing research questions to answer with available datasets, and 3) integrating Indigenous and Western ways of knowing. We have identified important considerations and suggestions for engaging and involving Indigenous communities and individuals in the generation of research ideas and analysis of linked data using community-based participatory research approaches through our work. These include engaging stakeholders at the start of the project and involving them throughout the research process, honouring Indigenous ways of knowing, the land, and local protocols and traditions, prioritizing Indigenous voices, promoting co-learning and building capacity, and focusing on developing longitudinal relationships. We describe keys to success and learnings that emerged. Importantly, the methodology practiced and presented in this manuscript is not a qualitative study design whereby research subjects are surveyed about their experiences or beliefs. Rather, the study approach described herein is about engaging people with living experience to co-lead as researchers. Our approach supported Indigenous people to share research that addresses their research priorities and responds to issues relevant to Indigenous Peoples and communities.

ABSTRACT We assessed the relationship between tobacco smoking and immunologic and virologic response among people living with HIV (PLWH) initiating combination antiretroviral therapy (cART) in the Canadian HIV Observational Cohort (CANOC). Positive immunologic and virologic response, respectively, were defined as ≥50 cells/mm3 CD4 count increase (CD4+) and viral suppression ≤50 copies/mL (VL+) within 6 months of cART initiation. Using multinomial regression, we examined the relationship between smoking, immunologic, and virologic response category. Model A adjusted for birth sex, baseline age, enrolling province, and era of cohort entry; models B and C further adjusted for neighbourhood level material deprivation and history of injection drug use (IDU), respectively. Among 4267 individuals (32.7%) with smoking status data, concordant positive (CD4+/VL+) response was achieved by 64.2% never, 66.9% former, and 59.4% current smokers. In the unadjusted analysis, current smoking was significantly associated with concordant negative response (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40–2.45). Similarly, models A and B showed an increased odds of concordant negative response in current smokers (adjusted OR [aOR] 1.78, 95% CI 1.32–2.39 and 1.74, 95% CI 1.29–2.34, respectively). The association between current smoking and concordant negative response was no longer significant in model C (aOR 1.18, 95%CI 0.85–1.65).

OBJECTIVES To determine the time to CD4 : CD8 ratio normalization among Canadian adults living with HIV in the modern ART era. To identify characteristics associated with ratio normalization. PATIENTS AND METHODS Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan-Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization. RESULTS Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62-0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11-0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5-1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization. CONCLUSIONS Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used.

Purpose: Centering Two-Spirit (2S) and Indigenous experiences and ways is critical for more respectful, reciprocal, relevant, and responsible sexual health research with gay, bisexual, and other men who have sex with men (gbMSM). The Two-Spirit Dry Lab, a collaborative initiative of Indigenous and settler researchers, conducted a study to explore drivers of sexual health knowledge with 2S and other Indigenous gbMSM community(ies). Methods: We used data from the 2015 Canadian Sex Now online survey. Our models balanced Indigenous ways of knowing with western epidemiology: we applied mitakuye oyasin (i.e., everything is related)—a Sioux teaching—alongside linear regression (i.e., certain relationships enable certain outcomes), to examine drivers of sexual health knowledge (a 6-point scale), comparing 2S and other Indigenous gbMSM. We also examined differences between those living in urban settings versus those living in non-urban ones. Results: Income and education were correlated, as were having a gay peer network, living in an urban setting, social support, and education. Income, education, gay peer network, and social support were associated with greater sexual health knowledge, as was younger age. In stratified analyses, living in an urban setting had a large and statistically significant association with sexual health knowledge for 2S men but not for other Indigenous men. Conclusions: Our study emphasizes the need to work with 2S and other Indigenous gbMSM to improve sexual health knowledge, focusing in particular on those with lower levels of income or educational attainment—who are less connected to gay peer networks—and older men.

Background: Stroke prevention therapy decisions for patients with atrial fibrillation (AF) are complex and require trade-offs, but few validated patient decision aids (PDAs) are available to facilitate shared decision making. Objective: To evaluate the effects of a novel PDA on decision-making parameters for AF patients choosing stroke prevention therapy. Methods: We developed an evidence-based individualized online AF PDA for stroke prevention therapy and evaluated it in a prospective observational pilot study. The primary outcome was decisional conflict. Secondary outcomes were knowledge, usability/acceptability, patient preferences, effects on therapy choices, and participant feedback. Results: 37 participants completed the PDA. The PDA could be completed independently and was well accepted. It significantly decreased the mean decisional conflict score (P < 0.001) and all its subscales and increased participant AF knowledge (P = 0.02). 76% of participants indicated that their individualized therapy attribute ranking was congruent with their values. The PDA-generated best-match therapy was chosen by 70% of participants in decision 1 (no therapy, aspirin, or oral anticoagulant), and 17% for decision 2 (choice of anticoagulant). Among AF patients, 60% chose a different drug than that currently prescribed to them. Conclusion and Relevance: Our PDA was effective for reducing decisional conflict, increasing patient knowledge, eliciting patients' values, and presenting therapy options that aligned with patients' values and preferences. Using the PDA revealed that many patients have therapy preferences different from their currently prescribed treatment. The PDA is a practical and potentially valuable tool to facilitate decision making about stroke prevention therapy for AF.

Summary Guidelines recommend that patients’ values and preferences should be considered when selecting stroke prevention therapy for atrial fibrillation (SPAF). However, doing so is difficult, and tools to assist clinicians are sparse. We performed a narrative systematic review to provide clinicians with insights into the values and preferences of AF patients for SPAF antithrombotic therapy. Narrative systematic review of published literature from database inception. Research questions: 1) What are patients’ AF and SPAF therapy values and preferences? 2) How are SPAF therapy values and preferences affected by patient factors? 3) How does conveying risk information affect SPAF therapy preferences? and 4) What is known about patient values and preferences regarding novel oral anticoagulants (NOACs) for SPAF? Twenty-five studies were included. Overall study quality was moderate. Severe stroke was associated with the greatest disutility among AF outcomes and most patients value the stroke prevention efficacy of therapy more than other attributes. Utilities, values, and preferences about other outcomes and attributes of therapy are heterogeneous and unpredictable. Patients’ therapy preferences usually align with their values when individualised risk information is presented, although divergence from this is common. Patients value the attributes of NOACs but frequently do not prefer NOACs over warfarin when all therapy-related attributes are considered. In conclusion, patients’ values and preferences for SPAF antithrombotic therapy are heterogeneous and there is no substitute for directly clarifying patients’ individual values and preferences. Research using choice modelling and tools to help clinicians and patients clarify their SPAF therapy values and preferences are needed. Supplementary Material to this article is available online at www.thrombosis-online.com.