Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population

Background Multimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized. Objectives To examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer. Methods We conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors. Results Of the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001. Conclusions Multimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics