Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

INTRODUCTION: In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. METHODS: This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. RESULTS: Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12 months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. CONCLUSIONS: Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma.

INTRODUCTION: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678). METHODS: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH). RESULTS: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3-4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001). CONCLUSION: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison.

BACKGROUND: There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. RESEARCH METHODS: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment. RESULTS: In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56-7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04-9.98]). These HRs increased to 5.16 (95% CI 3.61-7.38) and 6.56 (95% CI 4.01-10.72), respectively, in the secondary analysis. CONCLUSION: Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.

Boceprevir for Chronic Genotype 1 Hepatitis C Virus in the Current Health Care Setting in Greece: A Cost-effectiveness Analysis.

PURPOSE: Boceprevir, as an add-on to the standard of care (SOC) for chronic genotype 1 hepatitis C virus (G1 HCV), pegylated interferon + ribavirin for 48 weeks (PEG + RBV), has been reported to have a clinical profile superior to that of SOC alone. The objective of the present study was to compare the cost-effectiveness of triple therapy with PEG + RBV + boceprevir to that of SOC in treatment-naive and treatment-experienced patients with G1 HCV in Greece. METHODS: A Markov model that simulated the quality-adjusted life expectancy and corresponding costs of treating G1 HCV infection provided the basis of the analysis. Treatment strategies under consideration were those in the Phase III boceprevir trials: (1) boceprevir response-guided therapy (shortened treatment duration for early responders); (2) fixed-duration (4-week) SOC plus 44 weeks of triple therapy; and (3) 48-week SOC. Efficacy data and the baseline characteristics of the study population were based on data from the SPRINT-2 (Serine Protease Inhibitor Therapy 2) and RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) clinical trials. Health care resource utilization and costs reflect the local clinical setting, with a 3% discount per annum, and were assessed from a third-party payer perspective. FINDINGS: Triple therapy was projected to reduce liver complications (eg, decompensated cirrhosis, hepatocellular carcinoma, need for liver transplantation, and liver-related death) by 44% to 45% and 49% to 53% in treatment-naive and treatment-experienced patients, respectively, over a lifetime horizon, leading to corresponding gains of 0.87 and 1.25 quality-adjusted life-years gained per patient. Taking into account the costs of medications, treatment, and outcomes management, the estimated incremental cost-effectiveness ratios of triple therapy versus SOC were €10,003 and €10,852 per quality-adjusted life-years gained in treatment-naïve and treatment-experienced patients. Extensive sensitivity analyses suggested that the findings were robust over a wide range of inputs. IMPLICATIONS: Based on the findings from the present analysis, the addition of boceprevir to PEG + RBV for the treatment of patients with G1 HCV may be a cost-effective alternative in the health care setting in Greece.

Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

BACKGROUND: SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation. METHODS: A Markov model was used to estimate the incidence of liver complications, discounted costs (2010 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1. The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by: 1) placebo plus PR for 44 weeks (PR48); 2) BOC plus PR using response guided therapy (BOC/RGT); and 3) BOC plus PR for 44 weeks (BOC/PR48) and makes projections within and beyond the trial. HCV-related state-transition probabilities, costs, and utilities were obtained from previously published studies. All costs and QALYs were discounted at 3%. RESULTS: The model projected approximately 38% and 43% relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48, respectively. Treatment with BOC/RGT is associated with an incremental cost of $10,348 and an increase of 0.62 QALYs compared to treatment with PR48. Treatment with BOC/PR48 is associated with an incremental cost of $35,727 and an increase of 0.65 QALYs compared to treatment with PR48. The ICERs were $16,792/QALY and $55,162/QALY for the boceprevir-based treatment groups compared with PR48, respectively. The ICER for BOC/PR48 compared with BOC/RGT was $807,804. CONCLUSION: The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1. It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy. Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48.

Economic Evaluation of Boceprevir for the Treatment of Patients with Genotype 1 Chronic Hepatitis C Virus Infection in Hungary.

Background: Recent international, randomized, placebo-controlled clinical trials (SPRINT-2; RESPOND-2) demonstrated that the triple combination of peginterferon (PEG), ribavirin (RBV) and boceprevir (BOC) was more efficacious than the standard dual therapy of PEG and RBV in treatment of patients chronically infected with genotype 1 hepatitis C virus (HCV) infection. The objective of this study was to evaluate the cost-effectiveness of triple therapy in both treatment-naive and treatment-experienced patients in Hungary. Methods: A Markov model was developed to evaluate the long-term clinical benefits and the costeffectiveness of the triple therapy from the Hungarian payer perspective. Model states were fibrosis (F0-F4, defined using METAVIR fibrosis scores), decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), and liver-related deaths (LD). Efficacy was estimated from SPRINT-2 and RESPOND-2 studies. Disease progression rates and health state utilities used in the model were obtained from published studies. Estimates of probability of liver transplantation and cost were based on an analysis of the Hungarian Sick Fund database. All cost and benefits were discounted at 5% per year. Results: Compared to dual therapy, triple therapy was projected to increase the life expectancy by 0.98 and 2.42 life years and increase the quality-adjusted life years (QALY) by 0.59 and 1.13 in treatment-naive and treatment-experienced patients, respectively. The corresponding incremental cost-effectiveness ratios were HUF7,747,962 (€26,717) and HUF5,888,240 (€20,304) per QALY. The lifetime incidence of severe liver disease events (DC, HCC, LT, LD) were projected to decrease by 45% and 61% in treatment-naïve and treatment-experienced patients treated with triple therapy groups in comparison with PEG-RBV treatment. Conclusion: The addition of boceprevir to standard therapy for the treatment of patients with genotype 1 chronic HCV infection in Hungary is projected to be cost-effective using a commonly used willingness to pay threshold of HUF 8.46 million (3 times gross domestic product per capita).

Lower risk of hypoglycemia with sitagliptin compared to glipizide when either is added to metformin therapy: a pre-specified analysis adjusting for the most recently measured HbA(1c) value.

BACKGROUND: In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA(1c) value. METHODS: Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA(1c) value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects. RESULTS: Over the full range of HbA(1c) levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005). LIMITATIONS: The actual time between the HbA(1c) measurement and the hypoglycemic event was variable and not controlled for in the analysis. CONCLUSION: In pre-specified analyses adjusting for the most recently measured HbA(1c) value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.

Efficacy of the pentavalent rotavirus vaccine, RotaTeq®, in Finnish infants up to 3 years of age: the Finnish Extension Study.

Rotavirus Efficacy and Safety Trial (REST) enrolled nearly 70,000 infants, of whom more than 23,000 were from Finland. REST determined the efficacy of the pentavalent rotavirus vaccine (RV5) against rotavirus-related hospitalisations and emergency department (ED) visits in the first year after vaccination. Finnish infants initially in REST transitioned into the Finnish Extension Study (FES), where they were followed for rotavirus-related hospitalisations and ED visits through their second year of life and beyond. FES identified 150 (31%) additional rotavirus gastroenteritis (RVGE) cases beyond those identified in REST in the Finnish participants. Overall, RV5 reduced RVGE hospitalisations and ED visits, regardless of the rotavirus serotype, by 93.8% (95% confidence interval [CI]: 90.8-95.9%) for up to 3.1 years following the last vaccine dose. Vaccine efficacy against combined hospitalisations and ED visits between ages 4 months to 11 months, 12 months to 23 months, and 24 months to 35 months was 93.9% (95% CI: 89.1-96.9%), 94.4% (95% CI: 90.2-97.0%), and 85.9% (95% CI: 51.6-97.2%), respectively. The reduction of hospitalisations and ED visits due to any acute gastroenteritis, rotavirus or not, was 62.4% (95% CI: 57.6-66.6%) over the entire follow-up period. The results from FES confirm that RV5 induces high and sustained protection against rotavirus-related hospitalisations and ED visits, and has a very substantial impact on all gastroenteritis-related hospitalisations and ED visits into the third year of life in Finnish children.

Sustained efficacy of the pentavalent rotavirus vaccine, RV5, up to 3.1 years following the last dose of vaccine.

BACKGROUND: Rotavirus gastroenteritis (RVGE) is a common cause of childhood hospitalizations and emergency department (ED) visits. In the Rotavirus Efficacy and Safety Trial (REST), the pentavalent rotavirus vaccine (RV5) significantly reduced RVGE-associated hospitalizations and ED visits for up to 2 years following the last vaccine dose. This study evaluated whether RV5 remained efficacious beyond 2 years. METHODS: A total of 20,736 infants from Finland, initially in REST, were followed for RVGE-associated hospitalizations and ED visits in a Finnish extension study (FES) for up to 3.1 years after vaccination (age, ∼3.5 years). RESULTS: The FES added >18,500 person-years and captured 150 RVGE-associated hospitalizations and ED visits (11 RV5; 139 placebo). In REST + FES, RV5 reduced RVGE-associated hospitalizations and ED visits, regardless of rotavirus serotype, by 94.0% (95% confidence interval [CI]: 91.4%-95.9%) for up to 3.1 years after vaccination. RV5 also conferred significant protection against hospitalizations and ED visits associated with rotavirus serotypes G1 (95.5%; 95% CI: 92.8%-97.2%), G2 (81.9%; 95% CI: 16.1%-98.0%), G3 (89.0%; 95% CI: 53.3%-98.7%), G4 (83.4%; 95% CI: 51.2%-95.8%), and G9 (94.2%; 95% CI: 62.2%-99.9%). Rate reductions (95% CI) in hospitalizations and ED visits during the first, second, and third years of life were 94.0% (90.0%-96.5%), 94.7% (90.7%-97.2%), and 85.9% (51.6%-97.2%), respectively. CONCLUSIONS: RVGE-associated hospitalizations and ED visits remain common in the second year of life but decrease in the third year of life. RV5 showed sustained protective efficacy against RVGE-associated hospitalizations and ED visits, regardless of rotavirus serotype, for up to 3.1 years after vaccination.