Komal Gupte-Singh’s research while affiliated with Bristol-Myers Squibb and other places

Background Some patients lose response during treatment for moderate-to-severe ulcerative colitis (UC). We aimed to characterize real-world treatment failure patterns and associated economic burdens during use of first-line advanced therapies for UC. Methods IBM MarketScan Commercial and Medicare Supplemental Databases were used to identify adults initiating ≥ 1 advanced therapy for UC (January 1, 2010–September 30, 2019). Treatment failure was defined as augmentation with non-advanced therapy, discontinuation, dose escalation/interval shortening, failure to taper corticosteroids, UC-related surgery, or UC-related urgent care ≤ 12 months after treatment initiation. The index date was the date of treatment failure (treatment failure cohort) or 12 months after treatment initiation (persistent cohort). Treatment failure rates were assessed using Kaplan–Meier analyses. All-cause and UC-related healthcare resource utilization (HCRU) and costs 12 months post-index were also assessed. Results Analysis of treatment failure patterns included data from 6745 patients; HCRU and cost analyses included data from 5302 patients (treatment failure cohort, n = 4295; persistent cohort, n = 1007). In the overall population, 75% experienced treatment failure within the first 12 months (median: 5.1 months). Augmentation with non-advanced therapy (39%) was the most common first treatment failure event. The treatment failure cohort had significantly (P < .001) higher mean costs than the persistent cohort (all-cause, $74 995 vs$56 169; UC-related, $57 096 vs$47 347) mainly attributed to inpatient admissions and outpatient visits. Dose escalation/interval shortening accounted for the highest total costs ($101 668) across treatment failure events. Conclusions Advanced therapies for moderate-to-severe UC are associated with high rates of treatment failure and significant economic burden. More efficacious and durable treatments are needed.

Introduction: Despite availability of advanced therapies (ATs) for ulcerative colitis (UC), many patients fail to respond to treatment. This study examined real-world clinical and humanistic outcomes associated with current treatments in patients with UC. Methods: This cross-sectional study used US data from the Adelphi Real World Disease Specific Programme for inflammatory bowel disease from before (2017-2018) and during the COVID-19 pandemic (2020-2021). Physicians (gastroenterologists) seeing > 5 patients/month reported patients' disease characteristics, current symptoms and treatments, and reasons for treatment choices for their next seven consecutive patients aged ≥ 18 years with moderately to severely active UC before current treatment. Patients were asked to complete the EQ-5D-5L health-related quality of life (HRQoL) measure. ATs included tumor necrosis factor inhibitors (TNFis), integrin receptor antagonists, interleukin-12/23 antagonists, and Janus kinase inhibitors. Patients were classified as AT-naïve or AT-experienced based on current treatment received for ≥ 8 weeks and further classified as responders or non-responders based on symptoms, disease flare status, and remission. Descriptive analyses are presented. Results: The 2017-2018 cohort included 92 physicians and 539 patients (208 [38.6%] AT-experienced). The 2020-2021 cohort included 73 physicians and 448 patients (349 [77.9%] AT-experienced). TNFis were the most common ATs. In 2017-2018, 195 (58.9%) AT-naïve and 113 (54.3%) AT-experienced patients were non-responders; in 2020-2021 this was 57 (57.6%) and 182 (52.1%). Efficacy and induction of remission were physicians' most common reasons for AT choice. Dislike of injections/infusions was the most common reason for eligible patients not receiving biologic therapy. Numerically, non-responders (both AT-naïve and AT-experienced) had more symptoms, overall pain and fatigue, and lower HRQoL scores than responders. Conclusions: Before (2017-2018) and during the pandemic (2020-2021), over half of patients with UC did not respond to AT. Non-responders carried a high burden of disease. Alternative therapies are urgently needed to treat UC.

Introduction: This study assessed the cost-effectiveness of ozanimod compared with commonly used disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS). Methods: Annualized relapse rate (ARR) and safety data were obtained from a network meta-analysis (NMA) of clinical trials of RRMS treatments including ozanimod, fingolimod, dimethyl fumarate, teriflunomide, interferon beta-1a, interferon beta-1b, and glatiramer acetate. ARR-related number needed to treat (NNT) relative to placebo and annual total MS-related healthcare costs was used to estimate the incremental annual cost per relapse avoided with ozanimod vs each DMT. ARR and adverse event (AE) data were combined with drug costs and healthcare costs to manage relapses and AEs in order to estimate annual cost savings with ozanimod vs other DMTs, assuming a 1 million USD fixed treatment budget. Results: Treatment with ozanimod was associated with lower incremental annual healthcare costs to avoid a relapse, ranging from $843,684 vs interferon beta-1a (30 μg; 95$1,431,619, - $255,749) to$72,847 (95% CI - 153,444, 7750) vs fingolimod. Compared with all other DMTs, ozanimod was associated with overall healthcare cost savings ranging from $8257 vs interferon beta-1a (30 μg) to$2178 vs fingolimod. Compared with oral DMTs, ozanimod was associated with annual cost savings of $6199 with teriflunomide 7 mg,$4737 with teriflunomide 14 mg, $2178 with fingolimod, and$2793 with dimethyl fumarate. Conclusion: Treatment with ozanimod was associated with substantial reductions in annual drug costs and total MS-related healthcare costs to avoid relapses compared with other DMTs. In the fixed-budget analysis, ozanimod demonstrated a favorable cost-effective profile relative to other DMTs.

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.

Background: Ozanimod and ponesimod are sphingosine 1-phosphate receptor modulators approved by the U.S. Food and Drug Administration for treatment of relapsing forms of multiple sclerosis (MS). Given that no head-to-head trials have assessed these two treatments, we performed a matching-adjusted indirect comparison (MAIC) to compare efficacy and safety outcomes between ozanimod and ponesimod for MS. Methods: A MAIC compared efficacy and safety of ozanimod and ponesimod at 2 years. Outcomes included annualized relapse rate (ARR) and percentage change from baseline in brain volume loss (BVL) as well as rates of any treatment-emergent adverse events (TEAEs), serious adverse events (AEs), AEs leading to discontinuation, and other safety outcomes. Individual patient-level data were obtained for ozanimod from the RADIANCE-B trial, while aggregate-level patient data were obtained for ponesimod from the OPTIMUM trial. The MAIC was not anchored owing to lack of a common comparator across the two trials. The following characteristics were matched between the trials' populations: age, sex, time since MS symptom onset, relapses in prior year, Expanded Disability Status Scale score, disease-modifying therapies received in the prior 2 years, absence of gadolinium-enhancing T1 lesions, and percentage of patients from Eastern Europe. Results: After matching, key baseline characteristics were balanced between patients receiving ozanimod and ponesimod. Compared with ponesimod, ozanimod had a numerically lower ARR (rate ratio: 0.80 [95% CI: 0.57, 1.10]) and was associated with a significant reduction in BVL (% change difference: 0.20 [95% CI: 0.05, 0.36]). Additionally, ozanimod was associated with a significantly lower risk of TEAEs (risk difference: -11.9% [95% CI: -16.8%, -7.0%]), AEs leading to discontinuation (-6.1% [95% CI: -8.9%, -3.4%]), and lymphocyte count <0.2 K/μL (-2.3% [95% CI: -4.2%, -0.5%]). There were no statistically significant differences in the other safety outcomes. Conclusion: The MAIC results suggest that, compared with ponesimod, ozanimod is more effective in preserving brain volume, is comparable in terms of reducing relapse rates, and has a favorable safety profile.

Background Despite studies suggesting a high prevalence of cognitive impairment, depression, and fatigue (CDF) among patients with multiple sclerosis (MS), standardized CDF tools are used infrequently in clinical practice, potentially resulting in underdiagnosis. We documented the use of standardized tools to identify CDF in MS and sought to understand provider attitudes toward the tools and their use. Methods This mixed-methods study analyzed electronic health records (EHRs) from a large US urban MS center to determine the frequency and types of CDF screenings and numbers of MS treatment encounters (January 2018–December 2019). Participants included neurologists and nurse practitioners with ≥30 eligible patients and a convenience sample of adult MS patients (≥18 years) with ≥2 outpatient encounters during the study period. Semistructured provider interviews (n=6; principal investigator and 1 provider were excluded) were conducted, transcribed, coded, and analyzed to characterize screening patterns. Assessments included proportions of encounters and patients who had standardized CDF screenings, positive screening results, and documentation of a treatment recommendation, as well as provider attitudes toward tools and reported barriers and facilitators for use. Bivariate analysis was used to evaluate the relationship between screening rates and patient and provider covariates for groups with sufficient sample size (n=30). Results The final population included 260 unique patients, 489 outpatient encounters, and 8 providers. Of 260 patients (75% female, 83% aged <65 years), 24% (n=63) were screened with a depression tool. Only 2% (n=4) were screened with a tool measuring cognitive impairment, and none were screened with a tool measuring fatigue. Screening rates varied little by provider type. Higher depression screening rates were associated with white race (difference: 13.2%; 95% CI: 2.8%−23.5%; P=.01), ≤2 visits during the study period (difference: 7.6%; 95% CI: 0.6%−14.5%; P=.03), and provider experience >10 years (difference: 14.6%; 95% CI: 3.5%−25.8%; P=.01). Lack of support staff and perception of limited treatment options were commonly cited barriers to standardized screening in provider interviews. The higher rate of depression screening is likely driven by institutional culture and priorities. Conclusion Providers recognize the importance of CDF to patients, despite infrequent use of standardized screening. Integrating screening into institutional practices may enable ongoing tracking of assessment scores and provide a more comprehensive and longitudinal picture of symptom progression.