Novartis (Canada)

In multiple sclerosis, disease-modifying therapies aim to reduce relapse rate and slow disease progression. An important component of successful disease control is treatment persistence, which is the time a patient remains on a therapy. The primary objective of this study was to examine persistence with ofatumumab in a real-world setting. This was a retrospective cohort study using data from the Patient Support Program (clinicaltrials.gov number NCT06854341). Adults diagnosed with relapsing remitting multiple sclerosis who initiated ofatumumab were included. Persistence, defined as the number of days from ofatumumab initiation until discontinuation, was assessed from April 2021 to May 2024. Ofatumumab persistence was quantified by Kaplan-Meier estimates for discontinuation probabilities with corresponding 95% confidence intervals at 12, 24 and 36 months. Secondary objectives included a descriptive analysis of patients' baseline demographic and clinical characteristics, and their association with discontinuation. The PSP included a total of 6377 patients, of which 5436 patients met the inclusion criteria and had information to assess discontinuation. Persistence probability with ofatumumab was 96.94% at 12-months, 95.02% at 24-months, and 92.26% at 36-months post index. During this period, 167 patients (3.1%) discontinued ofatumumab. The most common reasons for discontinuation included side effects (0.9%), trying to conceive/pregnancy (0.5%), and patient request (0.5%). This study provides insights into real-world ofatumumab utilization among patients with multiple sclerosis and demonstrates that persistence with ofatumumab remained high over 3 years. These results complement data from controlled clinical trials and suggest that patients persist with ofatumumab.

Abstract Purpose: Understanding real-world treatment patterns and their effectiveness in HR+ HER2- advanced breast cancer (aBC) in Canadian patients. Patient and Methods: This was an observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR+/HER2- aBC receiving endocrine therapy (ET) or ET+ targeted therapy (ET+TT). The primary objective was duration of treatment (DOT) with ET and ET+TT. Sequence of therapies, treatment patterns, and Overall Survival (OS) were also evaluated. Results: DOT was prolonged in patients receiving ET+TT compared to ET (median DOT: ET+TT 397 days vs ET 192 days; Log-Rank test p-value <.0001; HR=0.66; 95% CI; 0.52,0.85). An extended DOT was observed in ET+CDK4/6i subgroup when compared to ET (median DOT: ET+CDK4/6i 601 days vs ET 192 days; Log-Rank test p-value <.0001). This increase was statistically significant irrespective of line of therapy at baseline (1L: median DOT: ET+CDK4/6i: 649 days vs ET: 217 days, p-value= <.0001; 2L: median DOT: ET+CDK4/6i: 487 days vs ET: 203 days, p-value= 0.0013; 3L: median DOT: ET+CDK4/6i: 597 days vs ET: 143 days therapy: p-value= 0.0006). ET alone and ET + CDK4/6i were the most frequently administered therapies in both 1st (ET alone: 43.5% and ET+CDK4/6i: 43.3%) and 2nd line (ET alone: 36.3% and ET+CDK4/6i: 24.6%). Among patients who received at least one CDK4/6i in 1st, 2nd, or 3rd line, CDK4/6i were mostly administered in 1st line (61.9%) and 2nd line (38.5%). ClinicalTrials.gov ID: NCT02753686; Registration Date:20-04-2016 Conclusion: Results support current treatment recommendations of early introduction of CDK4/6i in HR+/HER2- aBC.

The ruxolitinib compassionate use (CU) program offered ruxolitinib to patients ≥2 years of age with confirmed steroid-resistant acute or chronic graft-versus-host disease (aGvHD and cGvHD, respectively). Data from 1180 patients (n = 775, 370 and 35 with cGvHD, aGvHD, and non-specified GvHD, respectively) were analyzed. Most patients had severe cGvHD (56%) or stage III/IV aGvHD (70%) disease and had previously received corticosteroids ( > 80%); ruxolitinib was requested primarily as a second-/third-line option. Patients <12 and ≥12 years old most often received the recommended ruxolitinib doses (5 mg twice daily [BID] and 10 mg BID, respectively); however, 23% and 30% of ≥12 year olds with cGvHD and aGvHD, respectively, received the lower dose of 5 mg BID. Notably, corticosteroid usage decreased with ruxolitinib treatment; at the initial ruxolitinib request, 81% and 91% of patients with cGvHD and aGvHD, respectively, were receiving corticosteroids whereas at resupply, 62% and 64%, respectively, were receiving corticosteroids. Eighty two percent of evaluable patients with cGvHD had a complete or partial response to treatment and 56% of evaluable patients with aGvHD had a best response of grade 0/I. These findings demonstrate the rapid and positive effects of ruxolitinib in patients with GvHD in a real-world setting.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator’s Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

The association between physician-reported and patient-reported outcomes in patients with psoriasis is not adequately explored. Trends in PASI scores across body regions and the descriptive correspondence between physician-reported PASI components and patient-reported Psoriasis Symptom Diary are reported here. PURE is a prospective observational study in adult patients from Canada and Latin America with moderate-to-severe chronic plaque psoriasis. The study enrolled 2362 adult patients treated with secukinumab versus other approved therapies (1:1 ratio). The PASI total score, PASI sub-scores for erythema, thickening, and scaling, and PASI scores for each body region were evaluated and further correlated with disease impact using the Psoriasis Symptom Diary. Secukinumab treatment showed early reduction in the PASI total score (mean ± SD) from 13.3 ± 9.02 at baseline to 2.3 ± 3.99 at 3months; a similar trend was observed for PASI sub-scores for erythema (4.8 ± 3.21 to 0.9 ± 1.44), thickening (4.3 ± 3.00 to 0.7 ± 1.33) and scaling (4.2 ± 3.04 to 0.7 ± 1.30). The reduction in PASI total and sub-scores were sustained up to 36months. Psoriasis Symptom Diary component scores related to redness, cracking, and scaling showed a similar reduction from baseline at 3months that was also sustained up to 36months. PASI regional scores for each body region showed reduction at 3months with disease in the lower limbs being more treatment resistant. Safety profile of secukinumab was consistent with its established safety profile without any new or unexpected signals. Overall, an early and sustained resolution of erythema, thickening, and scaling was observed. Improvements were evident across all body regions, with the most persistent disease seen in the lower limbs. Trends in disease severity, as assessed by physicians using PASI, broadly reflected the trend in the comparable questions of the Psoriasis Symptom Diary assessed by patients.

We thank Dr. Tchetina for their interest in our article,1 and we appreciate the opportunity to respond to their Letter to the Editor.2 In the letter and their recent publication, Tchetina et al describe the utility of gene expression analyses using peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) to predict clinical response to tofacitinib (TOF).2,3.

To assess the real-world effectiveness, safety, and usage of erenumab in Canadian migraine patients who previously failed two to six categories of prophylactic migraine therapies.