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.

Impact of Atopic Dermatitis Lesion Location on Quality of Life in Adult Patients in a Real-world Study.

BACKGROUND: Atopic dermatitis (AD) has a negative impact on patients’ quality of life (QoL). OBJECTIVE: To report the impact of specific AD lesion locations on QoL in adult patients with AD using real-world data. METHODS: The Adelphi US Disease Specific Programme was conducted between January–April 2018. Physicians documented patient demographics/characteristics, AD lesion locations, and body surface area; patients completed questionnaires reporting the impact of lesion locations on QoL. RESULTS: AD severity was moderate in 51.6% of patients and severe in 6.0%. Lesions were commonly identified in more than one location. All AD lesion locations impacted QoL. Visible areas were most bothersome, including head/neck (68%), hands/fingers (58%), front (30%), upper extremities (22%), and lower extremities (16%), with statistically significant associations for a number of Dermatology Life Quality Index (DLQI) items. Itch, soreness, pain, and stinging are also associated with a number of body areas but in particular with those that are most visible/accessible. Lesions on the head/neck and hands/fingers (58%) demonstrated an increased impact on the anxiety and depression dimension of the EuroQol 5-Dimension tool. CONCLUSIONS: In patients with AD, quality of life was most affected in patients with lesions in visible areas, including head/neck, hands/fingers, and upper extremities, with statistically significant associations for a number of DLQI domains. Physicians should be aware of the burden of AD lesions on QoL and consider having conversations with patients to better understand the impact of these lesions. Prior presentation: 28th Annual European Academy of Dermatology and Venereology Congress; 9–13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.

Assessing the Impact of Losmapimod on Proteinuria in Idiopathic Focal Segmental Glomerulosclerosis.

INTRODUCTION: Idiopathic focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and end-stage renal disease. In preclinical models and biopsies of human FSGS kidneys, p38 mitogen-activated protein kinase (MAPK) has demonstrated enhanced activity; and p38 MAPK inhibition has improved disease markers. This proof-of-concept trial aimed to assess efficacy, safety, tolerability, and pharmacokinetics of losmapimod, an oral p38 MAPK inhibitor, in humans with FSGS. METHODS: A single-arm, multicenter, open-label, Phase II trial (NCT02000440) was conducted in adults with FSGS; proteinuria ≥2.0 g/d; estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2; blood pressure <140/90 mm Hg. Collapsing and genetic forms of FSGS were excluded. The primary endpoint was number of patients with ≥50% proteinuria reduction and eGFR ≥70% of baseline after receiving losmapimod twice-daily for 16 to 24 weeks. RESULTS: Seventeen patients received ≥1 losmapimod dose. No patients achieved the primary endpoint; therefore, the study was terminated following a prespecified interim analysis. At week 24, proteinuria reductions between 20% and <50% were observed in 4 patients and proteinuria increases >20% in 3 patients. One patient achieved a proteinuria response (≥50% reduction) at week 2 but subsequently relapsed. Losmapimod pharmacokinetics were consistent with prior studies. No serious adverse events (AEs) were reported. CONCLUSION: p38 MAPK inhibition with losmapimod did not result in ≥50% reduction of proteinuria in patients with FSGS. However, study population heterogeneity may have contributed to our negative findings and therefore this does not eliminate the potential to demonstrate benefit in a population more sensitive to p38 MAPK inhibition if identifiable in the future by precision-medicine methods.

Cost-effectiveness of fondaparinux versus enoxaparin in non-ST-elevation acute coronary syndrome in Canada (OASIS-5).

BACKGROUND: Acute coronary syndrome (ACS) refers to a spectrum of life-threatening cardiac diseases usually due to coronary artery plaque rupture, subsequent thrombin generation plaque activation and thrombus formation. To date, no economic analyses have been published about the use of fondaparinux in NSTE-ACS patients in Canada. The purpose of our study is to estimate the lifetime cost-effectiveness of fondaparinux compared to enoxaparin for non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in a Canadian hospital setting. METHODS: As an extension of a previous published economic analysis for US patients, an event-based decision analytic model was constructed using clinical and resource use data from OASIS-5, a randomized trial of 20,078 patients from 41 countries. A public payer perspective in the hospital setting was adopted. Resource use data from the trial were valued using Canadian costs. A cost regression model was developed to estimate the mean cost of managing the clinical events over the 180 day period. Annual costs of long-term care for ACS patients were added after 180 days until death. Long-term survival was incorporated using Canadian life tables with further adjustment for additional risks associated with NSTE-ACS. Quality-of-life (utility) decrements from published sources were applied to clinical events. Lifetime costs (2009 CAD$) and quality-adjusted life-years (QALYs), discounted annually at 5 %, were estimated for the typical patient in OASIS-5 (i.e., at mean covariate values). RESULTS: The trial data showed that fondaparinux is protective against all clinical events observed in the trial. The model showed that: over 180 days, fondaparinux dominates enoxaparin, producing similar estimates of QALYs gained and saving $439; over a patient's lifetime, fondaparinux yields an ICER of $4293/QALY. Based on PSA, the probabilities that fondaparinux dominates enoxaparin (less costly and more effective) and that is cost-effective at a $50,000 threshold were 42 % and 96 %, respectively. CONCLUSIONS: In the Canadian hospital setting, fondaparinux is cost-effective when compared to enoxaparin for the treatment of NSTE-ACS. This result holds both in the immediate post-event period and over the lifetimes of patients.