Clinical Outcomes Before and After Prucalopride Treatment: An Observational Study in Patients With Chronic Idiopathic Constipation in the United States.

INTRODUCTION: This real-world US-based claims study compared constipation-related symptoms and complications 6 months before and after prucalopride initiation in adults with chronic idiopathic constipation (CIC). METHODS: This observational, retrospective cohort analysis used the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database (January 2015-June 2020). Prucalopride-treated patients (≥18 years old) who had ≥1 constipation-related International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) diagnosis code during the baseline or study period were included. The proportions of patients with constipation-related symptoms (abdominal pain, abdominal distension [gaseous], incomplete defecation, and nausea) and constipation-related complications (anal fissure and fistula, intestinal obstruction, rectal prolapse, hemorrhoids, perianal venous thrombosis, perianal/perirectal abscess, and rectal bleeding) were examined. Constipation-related symptoms and complications were identified using ICD-10-CM , ICD-10 - Procedure Coding System , or Current Procedural Terminology codes. Data were stratified by age (overall, 18-64 years, and ≥65 years). RESULTS: This study included 690 patients: The mean (SD) patient age was 48.0 (14.7) years, and 87.5% were women. The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% vs 33.3%, P < 0.001]; abdominal distension [gaseous] [23.9% vs 13.3%, P < 0.001]; and nausea [22.6% vs 17.7%, P < 0.01]; no improvements observed for incomplete defecation). Similarly, the proportions of patients overall with constipation-related complications decreased 6 months after prucalopride initiation (intestinal obstruction [4.9% vs 2.0%, P < 0.001]; hemorrhoids [10.7% vs 7.0%, P < 0.05]; and rectal bleeding [4.1% vs 1.7%, P < 0.05]). DISCUSSION: This study suggests that prucalopride may be associated with improved constipation-related symptoms and complications 6 months after treatment initiation.

Comparison of health care costs and resource utilization for commonly used proteasome inhibitor-immunomodulatory drug-based triplet regimens for the management of patients with relapsed/refractory multiple myeloma in the United States.

BACKGROUND: Economic differences among currently available proteasome inhibitors (PI)-based lenalidomide-dexamethasone (Rd)-backbone triplet regimens-ixazomib (I), bortezomib (V), and carfilzomib (K) plus Rd-remain poorly understood. OBJECTIVE: To assess health care resource utilization (HCRU) and health care costs of patients with relapsed/refractory multiple myeloma (RRMM) in the United States treated with IRd, VRd, and KRd. METHODS: This retrospective longitudinal cohort study using IQVIA PharMetrics Plus adjudicated claims US data (January 1, 2015, to September 30, 2020) included adult patients with all available data who initiated IRd, VRd, or KRd in second line of therapy or later (LOT2+) on or after September 1, 2015. The index date was the treatment initiation date for each LOT (multiple LOTs per patient were included) and the baseline was 6 months pre-index. MM-related and all-cause HCRU/costs were assessed during follow-up and reported per patient per month (PPPM; 2020 US Dollars). For MM-related costs only, treatment administration costs were excluded from outpatient (OP) costs and instead summed with pharmacy costs. HCRU/costs were compared between treatment groups using generalized linear models (GLMs). Cost variables were compared using 2-part models and GLM with log transformation and γ distribution. Inverse probability of treatment weighting (IPTW) adjusted for imbalance of baseline confounders across treatment groups. RESULTS: The study included 511 patients contributing 542 LOTs (IRd: n = 153; VRd: n = 262; KRd: n = 127). Before IPTW, mean observed time spent on therapy was 8.5, 9.3, and 7.3 months for the IRd, VRd, and KRd cohorts, respectively. During follow-up and after IPTW, IRd and VRd were associated with significantly fewer OP visits vs KRd. Post-IPTW comparisons of MM-related costs for IRd vs KRd yielded lower OP costs for IRd (mean diff. PPPM: -$3,428; P < 0.001), contributing to lower total medical costs (-$3,813; P < 0.001) and total health care cost savings with IRd vs KRd (-$5,813; P = 0.001). MM-related OP costs were lower for VRd (mean diff. PPPM: -$3,543; P < 0.001) than KRd, reducing its total MM-related medical costs (-$3,997; P = 0.002), leading to total MM-related health care cost savings with VRd vs KRd (-$12,357; P < 0.001). All-cause cost comparisons yielded similar results (total health care cost savings for IRd and VRd vs KRd: -$6,371 and -$13,629, respectively; all P < 0.001). CONCLUSIONS: From the US insurance-payer perspective, patients treated with IRd and VRd had significant medical cost savings vs KRd due to lower OP costs when excluding treatment administration costs. The differential economic impacts of PI-Rd regimens in this study may help to inform treatment decisions for patients with MM. DISCLOSURES: This study and article were supported by Takeda Development Center Americas, Inc. Dr Sanchez has no conflicts to declare. Dr Chari has the following relationships: Research Support/Principal Investigator: Amgen, Array Biopharma, Celgene, Glaxo Smith Klein, Janssen, Millenium/Takeda, Novartis Pharmaceuticals, Oncoceutics, Pharmacyclics, Seattle Genetics; Consultant: Amgen, Bristol-Myers Squibb, Celgene, Millenium/Takeda, Janssen, Karyopharm; Scientific Advisory Board: Amgen, Celgene, Millenium/Takeda, Janssen, Karyopharm, Sanofi, Seattle Genetics. Drs Cherepanov, Huang, Dabora, and Noga are current employees of Takeda, while Drs Stull and Young are ex-employees of Takeda; Drs Cherepanov and Huang also own stocks in Takeda. Dr DerSarkissian, Ms Cheng, Ms Zhang, Mr Banatwala, and Dr Duh are employees of Analysis Group, Inc. (AG), a consulting firm that received funding from Takeda to conduct this study. Ms Pi was an employee of AG at the time of the study. Dr Ailawadhi has the following relationships to declare: Research Support and Consulting for BMS, GSK, and Janssen; Research Support from AbbVie, Arch Oncology, Cellectar, Medimmune, Pharmacyclics, and Xencor; Consulting for Beigene, Oncopeptides, Regeneron, Sanofi, and Takeda.

Impact of Therapy Management on Axitinib-Related Adverse Events in Patients With Advanced Renal Cell Carcinoma Receiving First-Line Axitinib + Checkpoint Inhibitor.

INTRODUCTION: There are limited real-world data on the effectiveness of strategies used to manage adverse events (AEs) in patients with advanced renal cell carcinoma (RCC) treated with axitinib. This retrospective chart review examined the AE profile and effect of axitinib modifications on AE resolution/improvement and treatment discontinuation. METHODS: A retrospective physician-administered chart review was conducted. Adult patients with advanced RCC treated with first-line axitinib plus checkpoint inhibitor (CPI) therapy (ie, avelumab or pembrolizumab) and who had documented frequently reported axitinib-related AEs of fatigue, diarrhea, nausea, hypertension, or palmar-plantar erythrodysesthesia were included. Physician characteristics, patient characteristics, AE characteristics, AE management strategies used, AE resolution/improvement, and treatment duration were described. The effect of strategies used to manage AEs (axitinib dose reduction or treatment interruption) on AE resolution/improvement was evaluated by logistic regression. RESULTS: Among 219 patients (median age: 62 years, 65% male), 70 (32%) were treated with axitinib + avelumab and 149 (68%) received axitinib + pembrolizumab. Axitinib modifications increased the likelihood of AE resolution/improvement compared with no modifications (adjusted odds ratio: 6.34, P < .001). In the subset of patients who discontinued treatment among those with or without axitinib modifications, mean treatment duration was 7.0 and 1.7 months, respectively. CONCLUSION: Toxicities experienced by patients with advanced RCC treated with first-line axitinib-CPI in the real world can be effectively managed by axitinib modifications, thereby prolonging treatment duration. (Clinicaltrials.gov identifier: NCT04682587).

Using Case Mix Index within Diagnosis-Related Groups to Evaluate Variation in Hospitalization Costs at a Large Academic Medical Center.

In analyzing direct hospitalization cost and clinical data from an academic medical center, commonly used metrics such as diagnosis-related group (DRG) weight explain approximately 37% of cost variability, but a substantial amount of variation remains unaccounted for by case mix index (CMI) alone. Using CMI as a benchmark, we isolate and target individual DRGs with higher than expected average costs for specific quality improvement efforts. While DRGs summarize hospitalization care after discharge, a predictive model using only information known before admission explained up to 60% of cost variability for two DRGs with a high excess cost burden. This level of variability likely reflects underlying patient factors that are not modifiable (e.g., age and prior comorbidities) and therefore less useful for health systems to target for intervention. However, the remaining unexplained variation can be inspected in further studies to discover operational factors that health systems can target to improve quality and value for their patients. Since DRG weights represent the expected resource consumption for a specific hospitalization type relative to the average hospitalization, the data-driven approach we demonstrate can be utilized by any health institution to quantify excess costs and potential savings among DRGs.