A modeling framework for the economic evaluation of baricitinib in moderate-to-severe rheumatoid arthritis

Objectives: The approval in more than 50 countries of baricitinib, an oral Janus Kinase inhibitor for the treatment of Rheumatoid Arthritis (RA), warrants a framework for corresponding economic evaluations. To develop a comprehensive economic model assessing the cost-effectiveness of baricitinib for the treatment of moderately-to-severely active RA patients in comparison to other relevant treatments, considering the natural history of the disease, real world treatment patterns, and clinical evidence from the baricitinib trials. Methods: A systematic literature review of previously developed models in RA was conducted to inform the model structure, key modeling assumptions and data inputs. Consultations with rheumatologists were undertaken to validate the modeling approach and underlying assumptions. Results: A discrete event simulation model was developed to international best practices with flexibility to assess the cost-effectiveness of baricitinib over a lifetime in a variety of markets. The model incorporates treatment sequencing to adequately reflect treatment pathways in clinical practice. Outcomes assessed include cost and quality-adjusted life years, allowing for a full incremental analysis of cost-effectiveness of competing treatments and treatment sequences. Conclusion: The economic model developed provides a robust framework for future analyses assessing the cost-effectiveness of baricitinib for the treatment of RA in specific country settings.</p

Additional file 1 of Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes

Additional file 1. Supplemental Methods and Tables S1-S9

Effects of Tirzepatide Versus Basal Insulins in People with Type 2 Diabetes and Different Baseline Glycemic Patterns: Post Hoc Analyses of the SURPASS-3 and SURPASS-4 Trials

Objective This post hoc analysis assessed change from baseline to Week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3) and glargine (SURPASS-4) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and post-prandial glucose (PPG). Research Design and Methods Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined using median values of these measures. Results All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG from baseline to Week 52 in all subgroups (p<0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (p<0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup. Conclusions In this post hoc analysis, tirzepatide was associated with superior glycemic control compared to insulin, irrespective of baseline glycemic pattern.</p

<strong>Dulaglutide and Kidney Function–Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis</strong>

Objective: Dulaglutide (DU) 1.5 mg was associated with improved composite renal outcomes that included new onset macroalbuminuria in people with type 2 diabetes with previous cardiovascular disease or cardiovascular risk factors in the REWIND trial. This exploratory post hoc analysis evaluated kidney-function-related outcomes, excluding the new onset macroalbuminuria component, among the REWIND participants. Research Design and Methods: Intent-to-treat analyses were performed on REWIND participants (N=4949 DU, N=4952 placebo). Time-to-occurrence of a composite kidney-function-related outcome (≥40% sustained decline in estimated glomerular filtration rate (eGFR, per the Chronic Kidney Disease Epidemiology Collaboration 2009 equation), end-stage renal disease, or renal-related death), and mean annual eGFR slope were examined. Analyses were conducted overall and within subgroups defined by baseline urinary albumin-to-creatinine ratio (UACR Results: The post hoc composite kidney-function-related outcome occurred less frequently among participants assigned to DU than placebo (Hazard Ratio (HR)=0.75, [95% Confidence Interval [CI]=0.62-0.92], p=0.004), with no evidence of a differential DU treatment effect by UACR or eGFR subgroup. A ≥40% sustained eGFR decline occurred less frequently among participants assigned to DU than placebo (HR=0.72, [95% CI=0.58-0.88], p=0.002). Mean annual decline in eGFR slope was significantly smaller for participants assigned to DU than placebo (-1.37 vs -1.56 mL/min/1.73 m2/year, p Conclusions: The estimated 25% reduced hazard of a kidney-function–related outcome among participants assigned to DU highlights its potential for delaying or slowing the development of diabetic kidney disease in people with type 2 diabetes.</p

Early-onset type 2 diabetes and tirzepatide treatment: a post hoc analysis from the SURPASS clinical trial program

Objective: We evaluated baseline characteristics of participants with early-onset T2D from the SURPASS program and tirzepatide’s effects on glycemic control, body weight (BW), and cardiometabolic markers. Research Design and Methods: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in participants (N=3792) with early-onset vs later-onset T2D at Week 40 (SURPASS-1, SURPASS-2) or Week 52 (SURPASS-3). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. Results: At baseline in SURPASS-2, participants with early-onset vs later-onset T2D were younger with longer diabetes duration (9 vs 7 years, p<0.001) higher glycemic levels (8.5% vs 8.2%, p<0.001), higher BW (97 vs 93 kg, p<0.001) and BMI (35 vs 34 kg/m2, p<0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs 156 mg/dL). At Week 40, similar improvements in HbA1c (-2.6% vs -2.4%), BW (-14 vs -13 kg), WC (-10 vs -10 cm), triglycerides (-26% vs -24%), HDL (7% vs 7%), and systolic BP (-6 vs -7 mmHg) were observed in both subgroups with tirzepatide. Conclusions: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline vs those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.</p

Early-Onset Type 2 Diabetes and Tirzepatide Treatment: A Post Hoc Analysis From the SURPASS Clinical Trial Program

OBJECTIVE We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide’s effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (−2.6% vs. −2.4%), BW (−14 vs. −13 kg), WC (−10 vs. −10 cm), triglycerides (−26% vs. −24%), HDL (7% vs. 7%), and systolic BP (−6 vs. −7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.</p