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Introduction Deutetrabenazine is approved for treatment of Huntington disease (HD)-related chorea and tardive dyskinesia (TD) in adults. Factors associated with deutetrabenazine persistence and adherence are not well understood. Methods Claims data from the Symphony Health Solutions Integrated Dataverse (2017-2019) were analyzed to identify real-world predictors of deutetrabenazine persistence and adherence in adults with HD or TD in the United States. Predictive models for persistence and adherence that considered patient demographics, payer type, comorbidities, treatment history, and health care resource use were developed. Results In HD, use of anticonvulsants (HR = 2.00 [95% CI = 1.03, 3.85]; P < .05), lipid-lowering agents (2.22 [1.03, 4.76]; P < .05), and Medicaid versus Medicare insurance (2.27 [1.03, 5.00]; P < .05) predicted persistence, whereas only comorbid anxiety disorders predicted discontinuation (0.46 [0.23, 0.93]; P < .05). Of these patients, 62.5% were adherent at 6 months. Use of 22642 treatments for chronic diseases (OR = 0.18 [95% CI = 0.04, 0.81]; P < .05) and Medicaid versus Medicare insurance (0.27 [0.09, 0.75]; P < .05) was associated with lower odds of adherence. In TD, use of lipid-lowering agents (HR = 4.76 [95% CI = 1.02, 20.00]; P < .05) predicted persistence, while comorbid schizoaffective disorder and/or schizophrenia (0.16 [0.14, 0.69]; P < .05) and sleep-wake disorders (0.18 [0.04, 0.82]; P < .05) predicted discontinuation. Of these patients, 46.7% were adherent at 6 months. Comorbid schizoaffective disorder and/or schizophrenia was associated with lower odds of adherence (OR = 0.26 [0.07, 0.91]; P < .05). Discussion Identifying factors predictive of discontinuation and/or nonadherence to deutetrabenazine may facilitate the development of personalized support programs that seek to improve outcomes in patients with HD or TD.

Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995-07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency). Patients in the PK deficiency cohort were matched 1:5 to patients from the general VHA population (non-PK deficiency cohort; index: random visit date during match's index year). OS from index was compared between the two cohorts. Eighteen patients in the PK deficiency cohort were matched to 90 individuals in the non-PK deficiency cohort (both cohorts: mean age 57 years, 94% males; median follow-up 6.0 and 8.0 years, respectively). At follow-up, patients in the non-PK deficiency cohort had significantly longer OS than the PK deficiency cohort (median OS: 17.1 vs. 10.9 years; hazard ratio: 2.3; p  = 0.0306). During their first-year post-index, 75% and 40% of the PK deficiency cohort had laboratory-confirmed anemia and iron overload, respectively. Among patients who died, cause of death was highly heterogeneous. These results highlight the increased risk of mortality and substantial clinical burden among patients with PK deficiency. While the intrinsic characteristics of the VHA database may limit the generalizability of the results, this is the first real-world study to characterize mortality in patients with PK deficiency.

Purpose: Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial., Methods: Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory., Results: After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF -mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%)., Conclusion: Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

Introduction: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3., Methods: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial's blinded phase only., Results: Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week 8., Conclusion: Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients., Trial Registration: ClinicalTrials.gov Identifier NCT03244644., (© 2024. The Author(s).)

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are oral alternatives to current standard-of-care treatments for anaemia in chronic kidney disease (CKD). We conducted network meta-analyses to indirectly compare clinical outcomes for three HIF-PHIs in dialysis and non-dialysis populations with anaemia in CKD., Methods: The evidence base comprised phase III, randomised, controlled trials evaluating daprodustat, roxadustat, or vadadustat. Three outcomes were evaluated: efficacy [change from baseline in haemoglobin (Hgb)], cardiovascular safety [time to first major adverse cardiovascular event (MACE)] and quality of life [change from baseline in 36-Item Short Form Health Survey (SF-36) Vitality score]. Analyses were performed separately for all patients and for erythropoiesis-stimulating agent (ESA) non-users at baseline (non-dialysis population) or prevalent dialysis patients (dialysis population). Bayesian Markov Chain Monte Carlo methods with non-informative priors were used to estimate the posterior probability distribution and generate pairwise treatment comparisons. Point estimates (medians of posterior distributions) and 95% credible intervals (CrI) were calculated., Results: Seventeen trials were included. In non-dialysis patients, there were no clinically meaningful differences between the three HIF-PHIs with respect to Hgb change from baseline [all patients analysis (total n  = 7907): daprodustat vs. roxadustat, 0.09 g/dL (95% CrI -0.14, 0.31); daprodustat vs. vadadustat, 0.09 g/dL (-0.04, 0.21); roxadustat vs. vadadustat, 0.00 g/dL (-0.22, 0.22)] or risk of MACE [all patients analysis (total n  = 7959): daprodustat vs. roxadustat, hazard ratio (HR) 1.16 (95% CrI 0.76, 1.77); daprodustat vs. vadadustat, 0.88 (0.71, 1.09); roxadustat vs. vadadustat, 0.76 (0.50, 1.16)]. Daprodustat showed a greater increase in SF-36 Vitality compared with roxadustat [total n  = 4880; treatment difference 4.70 points (95% CrI 0.08, 9.31)]. In dialysis patients, Hgb change from baseline was higher with daprodustat and roxadustat compared with vadadustat [all patients analysis (total n  = 11 124): daprodustat, 0.34 g/dL (0.22, 0.45); roxadustat, 0.38 g/dL (0.27, 0.49)], while there were no clinically meaningful differences in the risk of MACE between the HIF-PHIs [all patients analysis (total n  = 12 320): daprodustat vs. roxadustat, HR 0.89 (0.73, 1.08); daprodustat vs. vadadustat, HR 0.99 (0.82, 1.21); roxadustat vs. vadadustat, HR 1.12 (0.92, 1.37)]. Results were similar in analyses of ESA non-users and prevalent dialysis patients., Conclusions: In the setting of anaemia in CKD, indirect treatment comparisons suggest that daprodustat, roxadustat, and vadadustat are broadly clinically comparable in terms of efficacy and cardiovascular safety (precision was low for the latter), while daprodustat may be associated with reduction in fatigue to a greater extent than roxadustat., Competing Interests: A.S. is an employee of GSK. R.D.L. has received research support from Bristol Myers Squibb, GSK, Medtronic, and Pfizer; and consulting fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, GSK, Medtronic, Merck, Pfizer, and Portola. C.P.K. has received consulting fees from Abbott, Akebia, AstraZeneca, Bayer, Boehringer Ingelheim, Cara Therapeutics, CSL Behring, CSL Vifor, GSK, Pharmacosmos, ProKidney, Rockwell, Takeda, and Tricida, outside of the submitted work. A.C. has received research grants from CSL Vifor; consultancy fees from Astellas, AstraZeneca, Boehringer Ingelheim, CSL Vifor, GSK, Novo Nordisk, and Otsuka; speaker fees from Amgen, Astellas, AstraZeneca, Bayer, CSL Vifor, GSK, Novo Nordisk, and Sanofi (Mexico) and travel support from Astellas, AstraZeneca, and GSK, outside the submitted work. AC is also a member of the Catalan Registry of Renal Patients (RMRC). S.A.M was an employee of GSK at the time of the study. N.B. is an employee of, and shareholder in, GSK. T.J.K. is an employee of, and shareholder in, GSK. V.G.-H. is an employee of Analysis Group, Inc., which received funding from GSK to conduct this research. R.A. is an employee of Analysis Group, Inc., which received funding from GSK to conduct this research. R.R.C. is an employee of and shareholder in GSK. K.L.J. has received consulting fees from GSK, Vifor, and Akebia. A.J.S. has received consultancy fees from Analysis Group, Inc. I.D. has received research grants from Sanofi, NIHR Clinical Research Network (West Midlands, UK), and Kidney Research UK; and honoraria for advisory boards and speaker meetings from GSK, AstraZeneca, Sanofi, and Vifor., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America., Methods: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective., Results: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268., Conclusions: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers., (© 2023. The Author(s).)

Backgound: Lenalidomide-based regimens are commonly used for early relapse in patients with relapsed and/or refractory multiple myeloma (RRMM) receiving at least one prior line of therapy. In the absence of head-to-head comparison, matching-adjusted indirect comparison (MAIC) was conducted to demonstrate efficacy and safety of isatuximab+carfilzomib+dexamethasone (Isa-Kd) versus daratumumab + lenalidomide + dexamethasone (Dara-Rd) in RRMM., Methods: Patient-level data from IKEMA trial (Isa-Kd, n = 179) were matched to aggregate data from POLLUX (Dara-Rd, n = 286). Hazard ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) and overall survival (OS) were generated by weighted Cox proportional hazard models. Odds ratios (OR), 95% CI, and p-value were calculated for ≥very good partial response (≥VGPR) and treatment-emergent adverse events (TEAEs)., Results: After matching, no significant differences were observed between Isa-Kd and Dara-Rd in baseline characteristics except for patients with >3 prior lines (0.0% vs. 4.9%). Isa-Kd showed significantly better PFS (HR [95% CI]: 0.46 [0.24-0.86]; p = 0.0155), statistically non-significant improvement favoring Isa-Kd in OS (0.47 [0.20-1.09]; 0.0798), and ≥VGPR (OR [95% CI]: 1.53 [0.89-2.64]; p = 0.1252) than Dara-Rd. Odds of occurrence were significantly lower for some all-grade and grade 3/4 TEAEs with Isa-Kd than Dara-Rd., Conclusion: These results support Isa-Kd as an efficacious treatment for early relapse in non-lenalidomide refractory patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Approval of apalutamide, enzalutamide and darolutamide has transformed the treatment landscape and guideline recommendations for patients with nonmetastatic castration-resistant prostate cancer but now raises the issue of decision-making regarding treatment selection. In this perspective, we discuss the efficacy and safety of these second-generation androgen receptor inhibitors and propose that for patients with nonmetastatic castration-resistant prostate cancer, safety considerations for these treatments are especially important. We examine these considerations in the context of patient and caregiver preferences as well as patient clinical characteristics. We further posit that consideration of treatments' safety profiles should include not only the initial direct impacts from potential treatment-emergent adverse events and drug-drug interaction events, but also the full cascade of potentially avoidable healthcare complications.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited., Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD)., Results: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001)., Conclusion: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day., Competing Interests: The authors declare the following relationships, which may be considered as potential competing interests: Rajesh Pahwa has received consulting fees from AbbVie, Acadia, Acorda, Adamas, Cynapses, Global Kinetics, Lundbeck, Neurocrine, Pfizer, Sage, Sunovion, Teva Neuroscience, and US World Meds. He has received research grants from AbbVie, Adamas, Avid, Biotie, Boston Scientific, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, and Parkinson Study Group. Jason Aldred has been a consultant and received honorarium from AbbVie, Acorda, Adamas, Allergan, Boston Scientific, Teva, Medtronic, and US World Meds. He has also received research support from NINDS, Abbott, AbbVie, Acadia, Biogen, Boston Scientific, Denali, Impax/Amneal, Sunovion, Neuroderm, Novartis, and Theravance. Aristide Merola has received support from the NIH (KL2 TR001426) and speaker or consultancy honoraria from CSL Behring, AbbVie, Abbott, and Cynapsus Therapeutics. He has received grant support from Lundbeck and AbbVie. Prasanna L. Kandukuri, Yanjun Bao, Omar Ladhani, and Connie H. Yan are employees of AbbVie and may own stocks/shares in the company. Niodita R. Gupta is a former employee of AbbVie, currently employed by Johnson and Johnson, and may hold AbbVie stock. Vivek S. Chaudhari is a former employee of AbbVie, currently employed by EMD Serono, Inc. and may hold AbbVie stock. Emi Terasawa, Viviana Garcia-Horton, and David R. Steffen are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. Stuart H. Isaacson has received honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of: AbbVie, Acadia, Acorda, Adamas, Addex, Allergan, Amarantus, Axovant, Benevolent, Biogen, Britannia, Cerecor, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Intec Pharma, Ipsen, Jazz, Kyowa, Lundbeck, Michael J. Fox Foundation, Neurocrine, Neuroderm, Parkinson’s Study Group, Pharma2B, Roche, Sanofi, Sunovion, Teva, Theravance, UCB, US World Meds, and Zambon., (© 2022 The Author(s).)

Introduction: Three novel androgen receptor inhibitors are approved in the USA for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC): apalutamide, enzalutamide, and darolutamide. All three therapies have demonstrated prolonged metastasis-free survival in their respective phase III trials, with differing safety profiles. The objective of this study was to compare the mean per-patient costs of all-cause adverse events (AEs) requiring hospitalization between darolutamide versus apalutamide and enzalutamide for nmCRPC in the USA., Methods: All-cause grade ≥ 3 AEs with corresponding any-grade AEs reported among at least 10% of patients in any arm of the ARAMIS (darolutamide), SPARTAN (apalutamide), and PROSPER (enzalutamide) trials were selected for inclusion in the primary analyses. After matching-adjusted indirect comparison, AE costs were calculated by multiplying the AE rates from the trials by their respective unit costs of hospitalization taken from the US Healthcare Cost and Utilization Project (HCUP) database. Sensitivity analyses which further included any-grade AEs reported among at least 5% of patients were also performed., Results: After reweighting and adjusting for the trials' placebo arms, the mean per-patient AE costs were $1021 and $387 lower for darolutamide than for apalutamide and enzalutamide, respectively, over the trials' duration (SPARTAN and PROSPER, 43 months; ARAMIS, 48 months). For darolutamide vs. apalutamide, the largest drivers of the per-patient cost differences were fracture (adjusted difference $416), hypertension ($143), and rash ($219); for darolutamide vs. enzalutamide, they were fatigue not including asthenia ($290) and hypertension including increased blood pressure (i.e., any AE of hypertension or with elevated blood pressure not yet classified as hypertension) ($60). The results of the sensitivity analyses were consistent with the primary results., Conclusions: Patients with nmCRPC treated with darolutamide in ARAMIS incurred lower AE-related costs (USD), as determined using HCUP costing data, compared with patients treated with either apalutamide (in SPARTAN) or enzalutamide (in PROSPER)., (© 2022. The Author(s).)

Background: We compared real-world healthcare resource utilization (HRU), Crohn's disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic., Methods: Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan-Meier analyses, respectively., Results: Adalimumab- and vedolizumab-treated patients were matched ( n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline ( N ADA = 360, N VDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index ( N ADA = 143, N VDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001)., Conclusions: Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Introduction: A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL., Methods: Post hoc analyses of APD patient-diary data from the phase 3 randomized controlled trial were used to compare changes in time to ON-woTD after waking, motor-symptom control throughout the waking day, occurrence of extreme fluctuations between OFF and "on" with troublesome dyskinesia, and motor-state transitions with CLES versus IR-CL from baseline to week 12., Results: The sample included 33 CLES-treated and 30 IR-CL-treated patients. Among the CLES group, the percentage of patient days achieving ON-woTD within 30 min of waking was three times higher at week 12 versus baseline (33% vs. 11%, p = 0.0043); no significant change occurred with IR-CL. When the waking day was divided into four 4-h periods, CLES versus IR-CL treatment produced significantly greater reductions in OFF during three periods, and two periods had increased ON-woTD. Fewer CLES-treated patients had extreme fluctuations at week 12 (3% vs. 23%, p = 0.0224) compared to IR-CL-treated patients. From baseline to week 12, CLES-treated patients had greater reductions in the average number of motor-state transitions compared to IR-CL-treated patients (- 1.6, p = 0.0295)., Conclusion: CLES-treated patients experienced a more rapid onset of ON-woTD after waking and greater consistency of ON-woTD throughout their waking day than IR-CL-treated patients., (© 2022. The Author(s).)

Introduction: Chorea, a common clinical manifestation of Huntington's disease (HD), involves sudden, involuntary movements that interfere with daily functioning and contribute to the morbidity of HD. Tetrabenazine and deutetrabenazine are FDA-approved to treat chorea associated with HD. Compared to tetrabenazine, deutetrabenazine has a unique pharmacokinetic profile leading to more consistent systemic exposure, less frequent dosing, and a potentially more favorable safety/tolerability profile. Real-world adherence data for these medications are limited. Here, we evaluate real-world adherence patterns with the vesicular monoamine transporter 2 inhibitors, tetrabenazine and deutetrabenazine, among patients diagnosed with HD., Methods: Insurance claims data from the Symphony Health Solutions Integrated Dataverse (05/2017-05/2019) were retrospectively analyzed for patients diagnosed with HD (ICD-10-CM code G10). Patients were categorized into cohorts based on treatment. Outcomes included adherence, which was measured by proportion of days covered (PDC), adherence rate (PDC > 80%), and discontinuation rates during the 6-month follow-up period (after a 30-day dose stabilization period)., Results: Patient demographic characteristics between the deutetrabenazine (N = 281) and tetrabenazine (N = 101) cohorts were comparable at baseline. Mean ± SD PDC was significantly higher in the deutetrabenazine versus tetrabenazine cohort (78.5% ± 26.7% vs. 69.3% ± 31.4%; P < 0.01). Similarly, a higher adherence rate was observed in the deutetrabenazine versus tetrabenazine cohort, though the difference was not statistically significant (64.1% vs. 55.4%; P = 0.1518). Discontinuation rates were significantly lower in the deutetrabenazine versus tetrabenazine cohort during the 6-month follow-up period (1 month, 3.5% vs. 9.2%; 3 months, 14.7% vs. 23.3%; 6 months, 25.4% vs. 37.2%; P < 0.05)., Conclusions: Results from this real-world analysis indicate that patients treated with deutetrabenazine are more adherent to treatment and have lower discontinuation rates compared with patients in the tetrabenazine cohort. However, a potential limitation is overestimated adherence, as claims for prescription fills may not capture actual use. Additional research is warranted to explore the differences in adherence patterns between treatments, which may inform treatment decision-making., (© 2021. The Author(s).)

Purpose: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons., Materials and Methods: Individual patient data from the phase III ARAMIS trial (N PLACEBO =553; N DAROLUTAMIDE =943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (N PLACEBO =401; N APALUTAMIDE =806) and PROSPER (N PLACEBO =468; N ENZALUTAMIDE =933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival., Results: No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide., Conclusions: While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in prespecified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.

Importance: Demonstrating the value of therapies from a patient's perspective is increasingly important for patient-centered care., Objective: To compare patient-reported outcomes (PROs) with risankizumab vs ustekinumab and placebo in psoriasis symptoms, health-related quality of life (HRQL), and mental health among patients with moderate to severe psoriasis., Design, Setting, and Participants: The UltIMMa-1 and UltIMMa-2 studies were replicate 52-week phase 3, randomized, multisite, double-blind, placebo-controlled and active comparator-controlled trials conducted in 139 sites (including hospitals, academic medical centers, clinical research units, and private practices) globally in Asia-Pacific, Japan, Europe, and North America. Adults (≥18 years) with moderate to severe chronic plaque psoriasis with body surface area (BSA) involvement of 10% or more, Psoriasis Area Severity Index (PASI) scores of 12 or higher, and static Physician's Global Assessment (sPGA) scores of 3 or higher were included., Interventions: In each trial, patients were randomly assigned (3:1:1) to 150 mg of risankizumab, 45 mg or 90 mg of ustekinumab (weight-based per label) for 52 weeks, or matching placebo for 16 weeks followed by risankizumab., Main Outcomes and Measures: Integrated data from 2 trials were used to compare Psoriasis Symptom Scale (PSS) (total score and item scores for pain, redness, itchiness, and burning), Dermatology Life Quality Index (DLQI), 5-level EuroQoL-5D (EQ-5D-5L), and Hospital Anxiety and Depression Scale (HADS), at baseline, week 16, and week 52., Results: A total of 997 patients with moderate to severe chronic plaque psoriasis were analyzed. Across all arms, the mean age was 47.2 to 47.8 years and 68.3% (136/199 for ustekinumab) to 73.0% (146/200 for placebo) were men. Patients' characteristics and PROs were comparable across all treatment arms at baseline (n = 598, 199, 200 for risankizumab, ustekinumab, and placebo, respectively). At week 16, a significantly greater proportion of patients treated with risankizumab than those treated with ustekinumab or placebo achieved PSS = 0, indicating no psoriasis symptoms (30.3% [181/598], 15.1% [30/199], 1.0% [2/200], both P < .001), and DLQI = 0 or 1 indicating no impact on skin-related HRQL (66.2%, 44.7%, 6.0%, P < .001). Significantly greater proportions of patients treated with risankizumab achieved minimally clinically important difference (MCID) than ustekinumab or placebo for DLQI (94.5% [516/546], 85.1% [149/175], 35.6% [64/180]; both P < .001), EQ-5D-5L (41.7% [249/597] vs 31.5% [62/197], P = .01; vs 19.0% [38/200], P < .001), and HADS (anxiety: 69.1% [381/551] vs 57.1% [104/182], P = .004; vs 35.9% [66/184], P < .001; depression: 71.1% [354/598] vs 60.4% [96/159], P = .01; vs 37.1% [59/159], P < .001). At week 52, improvements in patients treated with risankizumab compared with those treated with ustekinumab were sustained for PSS, DLQI, and EQ-5D-5L., Conclusions and Relevance: Risankizumab significantly improved symptoms of moderate to severe psoriasis, improved HRQL, and reduced psychological distress compared with ustekinumab or placebo., Trial Registration: ClinicalTrials.gov Identifiers: NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2).

Background: Anti-tumor necrosis factor (TNF) therapies have been the mainstay of inflammatory bowel disease (IBD) treatment for nearly 2 decades. Therapies with novel mechanisms of action have been recently developed. This study compared healthcare resource utilization (HRU) and costs incurred while switching from an initial anti-TNF to another anti-TNF versus switching to vedolizumab., Methods: Adults with IBD who switched from initial anti-TNF to another anti-TNF or vedolizumab were identified from Truven MarketScan claims database (January 1, 2000-September 30, 2017). Patient characteristics were assessed during the 6-month period before the initiation date of the switched-to treatment (index date). Adjusted analyses of all-cause and disease-related HRU and costs during the 6-month period after the index date (study period) were performed. Anti-TNF and vedolizumab switchers with Crohn's disease (CD) and ulcerative colitis (UC) were separately compared., Results: A total of 502 vedolizumab, 1708 adalimumab, 755 infliximab, and 703 other switchers with CD and 461, 428, 311, and 148 with UC, respectively, were identified. Patient demographics were similar across cohorts. Total all-cause costs were significantly higher for vedolizumab than adalimumab, infliximab, and certolizumab switchers in the CD cohort and adalimumab and infliximab in the UC cohort. In both cohorts, adalimumab and other switchers had fewer all-cause and IBD-related outpatient visits than vedolizumab switchers., Conclusions: CD/UC patients who switched to vedolizumab from initial anti-TNF had higher total and treatment costs than patients who switched to another anti-TNF, except for UC patients who switched to golimumab. Prospective studies should be conducted to confirm these findings., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: There has been no single standard-of-care treatment of patients with advanced/metastatic soft tissue sarcoma (STS). This study was designed to understand patient and oncologist preferences in the advanced/metastatic setting., Methods: Adult patients diagnosed with STS and oncologists treating patients with STS completed discrete choice experiment surveys. Study participants chose between pairs of hypothetical treatment profiles for advanced STS characterized by varying levels of overall survival (14, 20, or 26 months), progression-free survival (3, 5, or 7 months), objective tumor response rate (12, 18, or 26%), risk of hospitalization due to side effects (12, 30, or 46%), and days/month to administer treatment (1, 2, or 4 days). A hierarchical Bayes model was used to estimate preferences and relative importance of attributes., Results: Seventy-six patients (23.7% male, mean age 52.8 years) and 160 oncologists (73.8% male, mean 16.9 years in practice) completed the surveys. Among patients, overall survival had the highest relative importance (39.5%, standard deviation [SD] 18.2%), followed by response rate (21.2%, SD 10.4%), and hospitalization (19.8%, SD 12.5%). Among oncologists, overall survival had the highest relative importance (44.6%, SD 16.0%), followed by hospitalization (18.4%, SD 8.3%)., Conclusions: Both patients with STS and oncologists preferred a treatment that maximizes the life of patients while avoiding hospitalizations.

Introduction: This study's objective was to describe characteristics, treatment patterns, and economic outcomes of type 2 diabetes mellitus (T2DM) patients initiating injectable antidiabetic medications in Japan., Methods: Adults (≥ 18 years) with T2DM, ≥ 2 claims for injectable antidiabetics between 1 August 2011 and 31 July 2015 (first claim = index date), no evidence of type 1 diabetes mellitus, ≤ 1 claim for insulin, no claims for GLP-1RA before index, and continuous enrollment for 6 months before (baseline) and 12 months after index (follow-up) were selected from the Japan Medical Center Database. Patient characteristics and outcomes during the baseline and follow-up periods were described overall and by provider, using the proxy setting of index medication [hospital (including outpatient departments) for specialists; clinic for general practitioner (GP)]., Results: Of the 2683 patients included (mean age: 50 years, 67% male), 1879 (70%) initiated injectable antidiabetics with specialists and 804 (30%) with GPs. The specialist cohort had a significantly greater comorbidity burden, but lower HbA1c levels during baseline, and was more likely to receive intensified treatment at index than the GP cohort. Almost 40% of patients (almost 30% of GP cohort) did not use antidiabetics during baseline; the remaining patients received oral medications, primarily from GPs. During follow-up, patients used the index medication for approximately 7 months. Independent of specialist vs. GP setting, patients received antidiabetics and medications for T2DM-related comorbidities and complications during the baseline and follow-up periods from the same provider, primarily GPs. The overall average healthcare costs were ¥350,404 during baseline and ¥1,856,727 during follow-up., Conclusions: In Japan, most T2DM patients initiated injectable antidiabetics with specialists vs. GPs. There were considerable differences in characteristics of patients treated by specialists vs. GPs. After initiation, injectable antidiabetics were largely prescribed by GPs. Future research should evaluate the factors associated with different provider practices and communication channels between specialists and GPs to improve patient management., Funding: Eli Lilly and Co.