Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study.

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product. The phase 2 TRANSCEND FL study evaluated liso-cel in patients with R/R FL, including 2L patients who all had POD24 from diagnosis after treatment with anti-CD20 antibody and alkylator ≤6 months of FL diagnosis and/or met modified Groupe d'Etude des Lymphomes Folliculaires criteria. Primary/key secondary endpoints were independent review committee-assessed overall response rate (ORR)/complete response (CR) rate. At data cutoff, 130 patients had received liso-cel (median follow-up, 18.9 months). Primary/key secondary endpoints were met. In third-line or later FL (n = 101), ORR was 97% (95% confidence interval (CI): 91.6‒99.4), and CR rate was 94% (95% CI: 87.5‒97.8). In 2L FL (n = 23), ORR was 96% (95% CI: 78.1‒99.9); all responders achieved CR. Cytokine release syndrome occurred in 58% of patients (grade ≥3, 1%); neurological events occurred in 15% of patients (grade ≥3, 2%). Liso-cel demonstrated efficacy and safety in patients with R/R FL, including high-risk 2L FL. ClinicalTrials.gov identifier: NCT04245839 .

Systematic Literature Review of Real-World Evidence on Dose Escalation and Treatment Switching in Ulcerative Colitis.

Background: Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching. Objective: We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib. Methods: We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017-2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching. Results: In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20-95% (1.8-36 months), clinical remission rates were 10-94% (1.8-36 months), colectomy rates were 0-33% (12-38 months), and adverse event rates were 0-18%. Treatment switching rates in 21 studies were 4-70% over 3-62 months, with switch due to loss of response rates of 4-35% over 12-62 months (7 studies). Up to 35% of patients underwent colectomy 12-120 weeks after switching, and 13-38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching. Conclusion: Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.

A Systematic Review of the Economic and Health-Related Quality of Life Impact of Advanced Therapies Used to Treat Moderate-to-Severe Ulcerative Colitis.

INTRODUCTION: The clinical benefits of advanced therapies (i.e., biologics and small-molecule drugs) in the treatment of moderate-to-severe ulcerative colitis (UC) have been demonstrated; however, there is less clarity regarding the economic and health-related quality of life (HRQoL) impact of these treatments. We conducted a systematic literature review to synthesize data on cost, healthcare resource utilization (HCRU), and HRQoL for patients who received approved advanced therapies for moderate-to-severe UC in the United States and Europe. METHODS: Databases including MEDLINE, Embase, the Database of Abstracts of Reviews of Effects (DARE), the National Health Service Economic Evaluation Database (NHS EED), and EconLit were searched systematically to identify observational studies published between January 1, 2010 and October 14, 2021 that assessed the impact of advanced therapies on cost, HCRU, and/or HRQoL in adults with moderate-to-severe UC. Supplementary gray literature searches of conference proceedings from the past 4 years (January 2018 to October 2021) were also performed. RESULTS: 47 publications of 40 unique cost/HCRU studies and 13 publications of nine unique HRQoL studies were included. Findings demonstrated that biologics have a positive impact on indirect costs (i.e., productivity, presenteeism, and absenteeism) and HRQoL. High costs of biologics were not always fully offset by reductions in cost and HCRU associated with disease management. For many patients, treatment switching and dose escalations were required, thus increasing drug costs, particularly when switching across treatment classes. CONCLUSION: These findings highlight a high unmet need for therapies for moderate-to-severe UC that can reduce the healthcare burden and impact on society. Further research is warranted, as the reported evidence was limited by the small sample sizes of some treatment groups within a study.

Although advanced therapies, such as biologics and small-molecule drugs, have shown clinical benefit in treating moderate-to-severe ulcerative colitis, their economic impact and effect on patients' quality of life is less clear. This study comprehensively reviewed the cost and use of healthcare resources associated with starting treatment with advanced therapies for ulcerative colitis, as well as the impact of these treatments on quality of life. We found that while biologics have a benefit on work productivity, work attendance, work absence, and quality of life, the high costs of biologics were not always fully met by reductions in disease management costs and healthcare resources. Many patients needed to switch treatments or required dose increases, which were expensive. There is a high unmet need for therapies for moderate-to-severe ulcerative colitis that can reduce healthcare costs, use of healthcare resources, and effect on society.

Endoscopic mucosal healing and histologic remission in ulcerative colitis: a systematic literature review of clinical, quality-of-life and economic outcomes.

OBJECTIVE: This systematic literature review (SLR) assessed the effects of endoscopic mucosal healing and histologic remission on clinical, quality-of-life (QoL), and economic outcomes in adults with ulcerative colitis (UC) in the real-world setting. METHODS: Literature searches of Embase and MEDLINE (6 July 2020) and conference proceedings (2017-2020) were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Eligible studies included adults with UC with documented endoscopic mucosal healing or histologic remission. Clinical, QoL, and economic outcomes were extracted and narratively synthesized. RESULTS: Of 1603 studies screened, 25 met eligibility criteria and collectively included 2813 patients (mean age: 34-60 years). The most commonly reported indices were Mayo endoscopic score (MES) for endoscopic mucosal healing (n = 22, 88%) and Geboes score (n = 5, 20%) for histologic outcomes. The most frequently reported clinical outcome was relapse-free survival (n = 15, 60%). Less commonly reported outcomes were avoidance of colectomy (n = 5, 20%), hospitalization (n = 4, 16%), clinical remission (n = 4, 16%), and steroid-free clinical remission (n = 3, 12%). Most studies reported relapse-free survival rates up to 50% over 6-48 months of follow-up in endoscopic mucosal healing cohorts. Studies reporting results by MES demonstrated higher relapse-free survival rates among patients with MES 0 than with MES 1 (32%-100% vs 26%-86%, respectively). Similarly, patients with histologic remission had better relapse-free survival rates over 12-24 months of follow-up compared with those without histologic remission (72%-91% vs 40%-63%, respectively). Rates of clinical remission, steroid-free remission, hospitalization, and colectomy avoidance were also better among patients with endoscopic mucosal healing and histologic remission. Two studies examining QoL reported endoscopic mucosal healing was associated with improved QoL. No study reported economic outcomes. CONCLUSIONS: This SLR demonstrated consistent evidence of improved clinical outcomes among UC patients with endoscopic mucosal healing and histologic remission.

Ulcerative colitis (UC) is a chronic, relapsing disease characterized by inflammation of the mucous membranes lining the rectum and colon. While medical management has traditionally focused on lessening UC symptoms, there is growing recognition that the reduction of underlying inflammation visible endoscopically (called endoscopic mucosal healing) or microscopically (called histologic remission) can be an objective indicator of disease improvement. This research is the first systematic literature review to assess the effects of endoscopic mucosal healing and histologic remission on clinical, quality-of-life (QoL), and economic outcomes in adults with UC in the real-world setting. We included studies in adults with UC who had mucosal healing or histologic remission and analyzed clinical, QoL, and economic outcomes using a technique called narrative synthesis. Twenty-five of 1603 studies screened met our eligibility criteria for inclusion in the analysis. In most studies, over 50% of patients with endoscopic mucosal healing did not relapse during follow-up, with better relapse-free survival rates reported among patients with a Mayo endoscopic scores of 0 than among those with a score of 1. Likewise, patients with histologic remission had higher relapse-free survival rates than those without histologic remission. Rates of clinical remission, steroid-free remission, hospitalization, and colectomy avoidance were better among patients with mucosal healing and/or histologic remission. Two studies also reported better QoL outcomes. Our findings suggest that endoscopic mucosal healing or histologic remission is associated with improved clinical and QoL outcomes. While more information is required, these measures should be considered important when making therapeutic decisions for patients with UC.

Patient and Neurologist Preferences in the United States for Relapsing-Remitting Multiple Sclerosis Treatments: Findings from a Discrete Choice Experiment.

BACKGROUND AND OBJECTIVE: Relapsing-remitting multiple sclerosis (RRMS) is a chronic inflammatory disease associated with central nervous system dysfunction and accelerated brain volume loss (BVL). There exists a paucity of research examining the importance of BVL to patients and neurologists and exploring whether such preferences may differ between these two groups. This study sought to evaluate the preferences of patients and neurologists for RRMS treatments by considering benefits and risks associated with novel and common disease-modifying therapies (DMTs). PATIENTS AND METHODS: US patients diagnosed with non-highly active RRMS and US-based neurologists completed an online cross-sectional survey. A discrete choice experiment was used to assess patient and neurologist treatment preferences, with neurologists considering preferences for patients with non-highly active RRMS. Respondents chose between two treatment profiles with seven attributes identified in qualitative research: 2-year disability progression; 1-year relapse rate; rate of BVL; and risks of gastrointestinal symptoms, flu-like symptoms, infection, and life-threatening events. Attribute-level weighted preferences were estimated using a hierarchical Bayesian model. RESULTS: Analyses included 150 patients with non-highly active RRMS (mean age: 54 years) and 150 neurologists (65% in private practice). Among patients, the most important treatment attribute was reducing the rate of BVL, followed by reducing the risk of infection and risk of flu-like symptoms. In contrast, the most important treatment attribute among neurologists was reducing the risk of a life-threatening event, followed by slowing the rate of 2-year disability progression and risk of infection. CONCLUSION: The findings highlight differences in treatment preferences between US patients and neurologists for non-highly active RRMS. The importance placed by patients on slowing the rate of BVL makes this a key topic that should be covered in the shared decision-making process.

Patient and neurologist preferences in the UK for relapsing-remitting multiple sclerosis treatments: findings from a discrete choice experiment.

OBJECTIVE: To evaluate and compare patient and neurologist preferences for relapsing-remitting multiple sclerosis (RRMS) treatments with respect to benefits and risks associated with common and novel disease-modifying therapies, including brain volume loss (BVL). METHODS: Patients with non-highly-active RRMS and neurologists in the United Kingdom completed an online cross-sectional survey. Patients completed one discrete choice experiment (DCE) exercise and providers completed two, one focusing on treatment for non-highly-active RRMS and another focused on highly active RRMS. Respondents chose between two treatment profiles that varied on seven attributes identified in qualitative research: 2 year disability progression; 1 year relapse rate; rate of BVL; and risks of gastrointestinal symptoms, flu-like symptoms, infection and life-threatening event. Bayesian modeling was used to estimate attribute-level weighted preferences. RESULTS: Patients (n = 144) prioritized slowing the rate of BVL, followed by reducing risk of infection, rate of 2 year disability progression and 1 year relapse rate. For non-highly-active patients, neurologists (n = 101) prioritized slowing the rate of BVL, followed by reducing 2 year disability progression, risk of infection and 1 year relapse rate. For highly active patients, neurologists prioritized lowering the 1 year relapse rate, followed by slowing the rate of BVL and 2 year disability progression. In all three DCEs, rate of BVL was approximately twice as important as reducing the risks of flu-like symptoms, gastrointestinal symptoms and life-threatening event. CONCLUSIONS: This study highlights similarities in treatment preferences for non-highly-active RRMS among patients and neurologists and differences in neurologists' preferences for treating non-highly-active vs. highly active RRMS. This research identifies BVL as a treatment outcome that should be discussed when physicians engage in shared decision-making with patients.

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis.

BACKGROUND: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS. METHODS: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. RESULTS: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI. CONCLUSION: In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

Comparative Efficacy and Safety of Ozanimod and Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis Using Matching-Adjusted Indirect Comparison.

BACKGROUND: Patients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited. OBJECTIVE: The aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population. METHODS: A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. RESULTS: After matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53-0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67-0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52-0.83), overall AEs (OR 0.11; 95% CI 0.08-0.16), SAEs (OR 0.27; 95% CI 0.19-0.39), and discontinuations (OR 0.11; 95% CI 0.07-0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62-1.26). CONCLUSIONS: After adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences.

Ozanimod and dimethyl fumarate (DMF) are disease-modifying therapies used to treat relapsing-remitting multiple sclerosis (MS). Comparative efficacy and safety evaluation is important to key patients, healthcare providers, and health insurers; however, head-to-head studies between MS therapies are limited. In this analysis, we used an indirect treatment comparison method, specifically a matching-adjusted indirect comparison (MAIC), to compare results of clinical trials of ozanimod and DMF. In this MAIC, findings suggested that ozanimod was associated with greater reductions of relapses, a lowered risk of disability progression at 3 months, and improved safety outcomes compared with DMF. Although MAICs were conducted while adjusting for important treatment-effect modifiers and/or prognostic factors, the possibility of confounding as a result of unobserved baseline differences remains. Such an issue can be resolved only by conducting a head-to-head treatment comparison in a randomized clinical trial.

Pharmacist-provided medication therapy management (MTM) program impacts outcomes for employees with diabetes.

The objective of this prospective, pre-post longitudinal study was to assess the impact of pharmacist-provided medication therapy management (MTM) services on employees' health and well-being by evaluating their clinical and humanistic outcomes. City of Toledo employees and/or their spouses and dependents with diabetes with or without comorbid conditions were enrolled in the pharmacist-conducted MTM program. Participants scheduled consultations with the pharmacist at predetermined intervals. Overall health outcomes, such as clinical markers, health-related quality of life (HRQoL), disease knowledge, and social and process measures, were documented at these visits and assessed for improvement. Changes in patient outcomes over time were analyzed using Wilcoxon signed rank and Friedman test at an a priori level of 0.05. Spearman correlation was used to measure the relationship between clinical and humanistic outcomes. A total of 101 patients enrolled in the program. At the end of 1 year, patients' A1c levels decreased on average by 0.27 from their baseline values. Systolic and diastolic blood pressure also decreased on average by 6.0 and 4.2 mmHg, respectively. Patient knowledge of disease conditions and certain aspects or components of HRQoL also improved. Improvements in social and process measures also were also observed. Improved clinical outcomes and quality of life can affect employee productivity and help reduce costs for employers by reducing disease-related missed days of work. Employers seeking to save costs and impact productivity can utilize the services provided by pharmacists.

Improving the economic and humanistic outcomes for diabetic patients: making a case for employer-sponsored medication therapy management.

BACKGROUND: The purpose of this study was to determine the cost savings of a pharmacist-led, employer-sponsored medication therapy management (MTM) program for diabetic patients and to assess for any changes in patient satisfaction and self-reported medication adherence for enrollees. METHODS: Participants in this study were enrollees of an employer-sponsored MTM program. They were included if their primary medical insurance and prescription coverage was from the City of Toledo, they had a diagnosis of type 2 diabetes, and whether or not they had been on medication or had been given a new prescription for diabetes treatment. The data were analyzed on a prospective, pre-post longitudinal basis, and tracked for one year following enrollment. Outcomes included economic costs, patient satisfaction, and self-reported patient adherence. Descriptive statistics were used to characterize the population, calculate the number of visits, and determine the mean costs for each visit. Friedman's test was used to determine changes in outcomes due to the nonparametric nature of the data. RESULTS: The mean number of visits to a physician's office decreased from 10.22 to 7.07. The mean cost of these visits for patients increased from $47.70 to $66.41, but use of the emergency room and inpatient visits decreased by at least 50%. Employer spending on emergency room visits decreased by $24,214.17 and inpatient visit costs decreased by $166,610.84. Office visit spending increased by $11,776.41. A total cost savings of $179,047.80 was realized by the employer at the end of the program. Significant improvements in patient satisfaction and adherence were observed. CONCLUSION: Pharmacist interventions provided through the employer-sponsored MTM program led to substantial cost savings to the employer with improved patient satisfaction and adherence on the part of employees at the conclusion of the program.