Denis Choquette

Objectives: The ROSA study evaluated real-world persistence and effectiveness of upadacitinib and tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA), using data from two Canadian registries, RHUMADATA and Ontario Best Practices Research Initiative (OBRI), and the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry. Methods: This observational study analysed data from 990 patients with RA who initiated upadacitinib or TNFi between 1 January 2020 and 30 June 2023. Multiple imputation was used for baseline covariates with missing data and results were adjusted for propensity scores derived from pre-specified variables (age, disease duration, prior treatments, comorbidities, etc.). Persistence was assessed using Kaplan–Meier and Cox proportional hazard regression models. Effectiveness was evaluated using observed (non-imputed) disease activity indices over 6 and 12 months. Results: Overall, 174, 216 and 600 patients were included from the RHUMADATA, OBRI, SCQM registries, respectively. Patients using upadacitinib had a lower risk of discontinuing treatment than patients using TNFi [hazard-ratio (HR) (95% CI): 0.602 (0.469, 0.773)] and this was unaffected by previous exposure to advanced treatment. Concomitant use of any csDMARD HR (95% CI); [upadacitinib: 0.225 (0.107, 0.471); TNFi: 0.516 (0.303, 0.881)], and methotrexate [upadacitinib: 0.604 (0.390, 0.934); TNFi: 0.694 (0.522, 0.925)] were associated with improved persistence for both groups. A similar proportion of patients receiving upadacitinib or TNFi achieved Clinical Disease Activity Index low disease activity or remission at 6 months (70.8% vs 61.0%; P = 0.1541) and 12 months (70.5% vs 75.2%; P = 0.4494). Conclusion: Canadian and Swiss patients with RA had longer persistence with upadacitinib than TNFi, independent of previous advanced treatments.

Objective: There is a key knowledge gap in quantifying residual disease activity in Canadian patients with axial spondyloarthritis (axSpA). The objective of this study was to evaluate and describe residual disease activity and burden of disease in Canadian patients with axSpA. Methods: This was an observational, retrospective analysis of data extracted from the Rhumadata (Québec), Spondyloarthritis Research Consortium of Canada (SPARCC; East/Atlantic and West regions, as well as Ontario), and Follow-up Research Cohort of Ankylosing Spondylitis (FORCAST; Alberta) registries. The primary endpoint was the proportion of patients who failed to achieve sustained low disease activity (LDA) at 12 months. LDA was defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score < 3 and sustained LDA was defined as achieving LDA at both 6 and 12 months after the most recent change in treatment. Analyses included outcomes by treatment class (nonsteroidal antiinflammatory drugs, tumor necrosis factor inhibitor, or interleukin 17 inhibitor). Results: A total of 980 patients (Rhumadata, N = 488; SPARCC, N = 239; FORCAST, N = 253) were included. Nearly half of patients with axSpA from Rhumadata (49.5%) and FORCAST (55.3%) and 65.8% of those from SPARCC failed to achieve LDA (BASDAI < 3) at 6 months after treatment initiation. At 12 months, failure to achieve sustained LDA rose to 62% in Rhumadata, 65.1% in FORCAST, and 81% in SPARCC. Pain persisted in nearly half of all patients. Conclusion: This analysis demonstrated that most Canadians with axSpA failed to achieve sustained LDA after 12 months of initiating their latest therapy and confirms a high unmet need for additional treatments.

Objective: Patients with inflammatory articular diseases, such as psoriatic arthritis (PsA), report weather changes in their symptoms. Our objective was to investigate the correlation between weather variation, disease activity (DA), and patient-reported outcomes (PROs) in patients with PsA.Methods: Hourly measurements of temperature, relative humidity, and pressure were obtained from 2015 to 2020 in Montreal (through Environment Canada) and were matched with DA and PROs of patients with PsA enrolled in Rhumadata. The differences in mean DA and PROs were examined between winter and summer. Pearson correlation coefficients were calculated between clinical profile and weather measurements.Results: Among patients with PsA, 2665 PROs were collected for a total of 858 patients. The Clinical Disease Activity Index (P= 0.001) and Simplified Disease Activity Index (P< 0.001) were lower in winter. In summer, positive correlations were found between humidity and symptoms (using patient global assessment, fatigue, pain, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index), whereas negative correlations between temperature and Health Assessment Questionnaire–Disability Index were reported. In winter, positive correlations were observed between temperature, fatigue, and pain.Conclusion: This is the first study to investigate weather variations through subjective and objective PROs matched with patients with PsA. Statistically significant differences in clinical profile were evident between winter and summer, as well as in their correlation with weather measurements. However, these distinctions lack clinical significance, suggesting a small impact on patients with PsA.

Background: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe RA. Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first TNF inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA. Methods: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up or 25 November 2022. Kaplan–Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted and propensity score-adjusted imputed data analyses were produced. Results: Six hundred eleven patients [320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)] were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44–0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18–0.84) had better retention than TNFi after adjusting for patient characteristics. Conclusion: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.

Objective: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA.Methods: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies.Results: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East.Conclusion: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment.

Objective: Axial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population.Methods: This was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices.Results: A total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months.Conclusion: The results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis.

Objective: Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA.Methods: This was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices.Results: In total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively.Conclusion: This is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

Objective: To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.Methods: The 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998–2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively.Results: In total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57–5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01–4.67), and second bDMARD or tsDMARD (range 3.71–4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18–40%) or dual therapy (34%, range 29–42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10–32%), dual therapy in 49% (range 39–56%), and bDMARD or tsDMARD in 24% (range 15–28%). The first bDMARD was an anti–tumor necrosis factor in 79% (range 78–82%).Conclusion: Canadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

Background: Recent approvals for novel agents such as the small molecule Janus kinase inhibitors (JAKi), combined with the advent of biosimilars has widened the gamut of available therapeutic options in the treatment of rheumatoid arthritis (RA). This combined with the introduction of mandatory non- medical switches to biosimilars in some jurisdictions by both public and private payors has led to a significant increase in the volume of therapeutic changes for patients. Pharmacists are well positioned to ensure effective and safe transitions, however there is a significant unmet need for objective and subjective clinical guidance around therapy as well disease state monitoring in RA that facilitates best practices throughout the patient journey. Objective: In this paper we aim to create a consensus derived monitoring algorithm for pharmacists to facilitate best practices throughout therapeutic transitions from originator biologic to other originator biologics, biosimilars, and Janus kinase inhibitors in RA. Methods: The Nominal Group Technique (NGT) was used to understand if consensus could be found among the participants. Clinically relevant questions were developed to capture solutions to the identified unmet need. The faculty considered the questions as individuals, and privately generated answers/ideas. After discussion and consideration, the participants ranked the ideas and established a consensus. Results: Based on the outcome of the consensus discussions, an algorithm was created to help guide pharmacists through therapeutic transitions in RA. The tool covers important topics such as pre-transition considerations, avoiding the nocebo effect for biosimilars, specific considerations for each drug or class, monitoring efficacy, and when to refer. Conclusions: New classes of anti-rheumatic drugs including JAKi, along with the introduction of biosimilars are presenting more opportunity for therapeutic changes and monitoring in patients with RA. We hope our evidence-based consensus derived guidance tool will assist frontline pharmacists in supporting their patients to a successful therapeutic transition in RA.

Treatment persistence is an important consideration when selecting a therapy for chronic conditions such as rheumatoid arthritis (RA). We assessed the long-term persistence of abatacept or a tumor necrosis factor inhibitor (TNFi) following (1) inadequate response to a conventional synthetic disease-modifying antirheumatic drug (first-line biologic agent) and (2) inadequate response to a first biologic DMARD (second-line biologic agent). Data were extracted from the Rhumadata® registry for patients with RA prescribed either abatacept or a TNFi (adalimumab, certolizumab, etanercept, golimumab, or infliximab) who met the study selection criteria. The primary outcome was persistence to abatacept and TNFi treatment, as first- or second-line biologics. Secondary outcomes included the proportion of patients discontinuing therapy, reasons for discontinuation, and predictors of discontinuation. Persistence was defined as the time from initiation to discontinuation of biologic therapy. Baseline characteristics were compared using descriptive statistics; cumulative persistence rates were estimated using Kaplan-Meier methods, compared using the log-rank test. Multivariate Cox proportional hazard models were used to compare the persistence between treatments, controlling for baseline covariates. Overall, 705 patients met the selection criteria for first-line biologic agent initiation (abatacept, n = 92; TNFi, n = 613) and 317 patients met the criteria for second-line biologic agent initiation (abatacept, n = 105; TNFi, n = 212). There were no clinically significant differences in baseline characteristics between the treatments with either first- or second-line biologics. Persistence was similar between the first-line biologic treatments (p = 0.7406) but significantly higher for abatacept compared with TNFi as a second-line biologic (p = 0.0001). Mean (SD) times on first-line biologic abatacept and TNFi use were 4.53 (0.41) and 5.35 (0.20) years, and 4.80 (0.45) and 2.82 (0.24) years, respectively, as second-line biologic agents. The proportion of patients discontinuing abatacept and TNFi in first-line was 51.1% vs. 59.5% (p = 0.1404), respectively. In second-line, it was 57.1% vs. 74.1% (p = 0.0031). The main reasons for stopping both treatments were inefficacy and adverse events. Abatacept and TNFi use demonstrated similar persistence rates at 9 years as a first-line biologic agent. As a second-line biologic agent, abatacept had better persistence rates over a TNFi.