Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study.

To describe the characteristics of patients receiving belimumab, overall patterns of systemic lupus erythematosus (SLE) care, clinical outcomes, and changes in glucocorticoid dose following 6 months of therapy with belimumab, and healthcare resource utilization in belimumab users in Canadian clinical practice settings. Retrospective multicenter medical chart review study of adult patients with SLE who were prescribed belimumab as part of usual care and who received ≥8 infusions or 6 months of treatment. Primary endpoints included physician-determined overall clinical improvement from baseline, glucocorticoid use, and physician-determined SLE disease severity at Month 6. In total, 52 patients were included in the study. At belimumab initiation, 5.8/76.9/17.3% of patients had mild/moderate/severe SLE, respectively. Oral glucocorticoids were discontinued in 11.4% of patients and 59.1% received a lower dose at Month 6. At Month 6, 80.8/57.7/17.3% of patients had a physician-determined clinical improvement of ≥20/≥50/≥80%, respectively. Sixteen patients had a SLE Disease Activity Index-2K score at both baseline and Month 6, with a mean improvement of 2.6 ± 5.3 from 8.1 ± 3.2 at baseline. No formal disease assessment tool was utilized for 42.3% of study patients at baseline. This study provides the first real-world insights into belimumab use in Canada. It demonstrates significant reduction or discontinuation of glucocorticoid dose in 70.5% of patients and clinically significant improvement following 6 months' belimumab therapy. The high number of patients with no formal disease activity assessments highlights a key care gap in SLE treatment in the real-world setting.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Effect of Disease Activity on Organ Damage Progression in Systemic Lupus Erythematosus: University of Toronto Lupus Clinic Cohort.

OBJECTIVE: To examine the role of disease activity on organ damage over 5 years in patients with active systemic lupus erythematosus (SLE) despite standard of care. METHODS: This analysis of the University of Toronto Lupus Clinic cohort assessed organ damage [measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] in patients with active SLE [SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 6], using Cox proportional time-independent hazard models. Subgroup analyses were conducted in patients with SLEDAI-2K 6 or 7, 8 or 9, and ≥ 10 at baseline, and in the overall study population by steroid dose at study entry (< 7.5 vs ≥ 7.5 mg/day). RESULTS: Among the overall study population (n = 649), SDI progression was observed in 209 (32.2%) patients over the 5-year follow-up period. Mean SDI change in patients with a score > 0 was generally consistent across all SLEDAI-2K subgroups. Multivariable analyses identified age at study start (HR 1.03, P < 0.0001), steroid dose (HR 2.03, P < 0.0001), immunosuppressants (HR 1.44, P = 0.021), and SLEDAI-2K (subgroup analyses HR 1.64-2.03, P = 0.0017 to < 0.0001) as the greatest risk factors for SDI progression, while a study start date after the year 2000 had a protective effect on SDI progression compared with a start date prior to the year 2000 (HR 0.65, P = 0.0004). CONCLUSION: Patients within the higher SLEDAI-2K subgroups at study entry or receiving high doses of steroids were more likely to have organ damage progression.

Persistent Disease Activity Remains a Burden for Patients with Systemic Lupus Erythematosus.

OBJECTIVE: Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time. METHODS: Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K. RESULTS: There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years. CONCLUSION: Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Rosiglitazone use and associated adverse event rates in Canada: an updated analysis.

BACKGROUND: We previously reported on the change in the use of rosiglitazone-containing products (RCP) and adverse event reporting rates in Canadian patients between 2004 and 2010. The present study extends this analysis to include the January 2011 to December 2012 time period. METHODS: RCP utilization rates were obtained from IMS Health Brogan's longitudinal de-identified patient database, LRx. GlaxoSmithKline's global adverse events database was used to extract adverse events (AE), serious adverse events (SAE), and cardiac adverse events (CAE) reported in Canadian patients receiving RCP from April 2004 to December 2012. The patient utilization information from the LRx database was used to estimate rates per 100,000 patients. RESULTS: An estimated 182,841 patients were dispensed RCP prescriptions between April 2004 and December 2012. The total number of patients using RCP decreased by 85% from 2011 to 2012. From its peak use in 2007, the number of patients filling a prescription decreased 97%. A total of 1069 AEs were reported during the study period, of which 32 AE's were reported from Jan 2011 to Dec 2012. The average monthly reporting rates of AE's, SAE's and CAE's over 2011-2012 were 10.8/100,000 patients, 9.1/100,000 patients and 5.0/100,000 patients, respectively. CONCLUSIONS: The utilization of RCP in Canada has significantly declined. The significance of the adverse event rate information presented is uncertain and must be evaluated within the context of the well known factors that can influence AE reporting rates, as well as limitations to the methods used to estimate these reporting rates.