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James F Donohue,1 Keith A Betts,2 Ella Xiaoyan Du,2 Pablo Altman,3 Pankaj Goyal,4 Dorothy L Keininger,4 Jean-Bernard Gruenberger,4 James E Signorovitch5 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina, Chapel Hill, NC, 2Analysis Group, Inc., Los Angeles, CA, 3Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland; 5Analysis Group, Inc., Boston, MA, USA Purpose: Long-acting β2-agonists (LABAs) have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.Methods: A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 µg twice daily [BID]; formoterol 12 µg BID; indacaterol 75, 150, and 300 µg once daily [OD]; olodaterol 5 and 10 µg OD, and vilanterol 25 µg OD). Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1), transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.Results: At 12 and 24 weeks, indacaterol 300 and 150 µg OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 µg OD was superior to formoterol 12 µg BID. At 12 weeks, indacaterol 75 µg OD was associated with significant improvement in trough FEV1 compared to formoterol 12 µg BID and olodaterol (5 and 10 µg OD); salmeterol 50 µg BID was superior to formoterol 12 µg BID and olodaterol 5 µg OD. Indacaterol 300 µg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150 µg OD had significantly better results in exacerbation rates than olodaterol 5 µg and olodaterol 10 µg OD.Conclusion: Indacaterol 300 µg, followed by 150 and 75 µg, were the most effective LABA monotherapies for moderate to severe COPD. Keywords: COPD, long-acting β2-agonists, network meta-analysis, systematic literature review, indacaterol

Objective: Patients with type 2 diabetes (T2D) are at high risk for developing chronic kidney disease (CKD). The onset of incident CKD may complicate glycemic control among these patients. This study aimed to characterize antihyperglycemic medication use after incident CKD onset among patients with T2D to inform disease management., Study Design: Retrospective cohort study., Methods: Patients with incident CKD and prior T2D were identified from the Optum electronic health records database between March 2013 and September 2021. Patterns of antihyperglycemic use were assessed during the 1-year baseline period and after incident CKD diagnosis and described by baseline hemoglobin A1C (HbA1C) level (controlled [< 7%] vs elevated [≥ 7%]) and CKD severity., Results: The study consisted of 262,395 patients, of whom 51% had elevated HbA1C. After CKD onset, 23.9% of patients initiated new antihyperglycemics within 1 year. Patients with elevated HbA1C had shorter time to new treatment initiation compared with those with controlled HbA1C (median, 28.7 vs 83.7 months). Patients with elevated urine albumin-to-creatinine ratio (uACR) had shorter median time to new treatment initiation (39.9-42.4 months) than those with normal uACR (59.8 months). Less than 7% of patients with stage 3 CKD and even smaller percentages of patients with higher stages of CKD utilized glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors., Conclusions: Treatment of T2D was considerably heterogenous by HbA1C level and CKD severity in patients with incident CKD. Current agents may not sufficiently fulfill the unmet need of T2D management in patients with CKD.

Introduction: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months., Methods: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24 months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared., Results: Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months 7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months 13-18 included 119 and 48 patients, respectively; and months 19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months 1-6; $26,840 versus $27,983, respectively, in months 7-12; $22,899 versus $25,137 in months 13-18; and $22,279 versus $27,947 in months 19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months 1-6; $25,144 versus $26,692, respectively, in months 7-12; $21,645 versus $23,709 in months 13-18; and $20,486 versus $25,515 in months 19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months 19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months 7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months 7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125)., Conclusion: Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6 months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months 7 to 24., (© 2024. The Author(s).)

Background: There is limited real-world data regarding subsequent treatment utilization and clinical outcomes following initial androgen receptor pathway inhibitor (ARPI) exposure for the treatment of advanced prostate cancer. This study aimed to address this evidence gap., Methods: Electronic health records during 01/01/2013-07/31/2022 from Flatiron Health were used to identify adults with mCRPC, who had prior exposure to ARPIs (irrespective of the setting) and ≥1 post-ARPI line of therapy (LOT) in the mCRPC setting (index therapy: the first eligible LOT in the mCRPC setting). Treatment patterns and survival outcomes following the initiation of index therapy were reported., Results: Among 804 ARPI-experienced mCRPC patients, 459 patients (57.1%) received another ARPI as their index therapy and 192 (23.9%) received chemotherapy as their index therapy. In the overall population, median time on the index therapy and median time from index therapy to next therapy were 4.1 and 6.2 months, respectively. Median overall survival and radiographic progression-free survival from the initiation of index therapy were 15.1 and 7.0 months, respectively., Conclusions: In this real-world analysis, more than half of patients attempted at least 1 additional ARPI in the mCRPC setting, despite prior treatment with ARPIs. The short treatment duration and survival time highlight the unmet need for additional, effective therapies that may improve clinical outcomes in this population., Competing Interests: Disclosure VN received research grant (to institution) from Pfizer, Janssen Oncology, Merck, Regeneron, Bristol-Myers Squibb, Xencor, TMunity Therapeutics; and advisory board/consulting fees from Bristol-Myers Squibb, Pfizer, Janssen Oncology, Exelixis, Myovant Sciences, Regeneron, Amgen, Eisai, AstraZeneca. MYP, ST, and LR are employees of Bristol Myers Squibb who may own stock/stock options. XY is a real-world evidence consultant at Bristol Myers Squibb. KAB, IP, SG, and MS, are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Bristol Myers Squibb, which funded the development and conduct of this study and manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Nivolumab is approved as adjuvant therapy for resected stage III/IV melanoma based on the phase 3 CheckMate 238 trial. This analysis compared outcomes from CheckMate 238 with those from the real-world Flatiron Health electronic health record-derived de-identified database in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab., Materials: Outcomes included baseline characteristics, overall survival (OS) in the CheckMate 238 cohort (randomization until death or last known alive), and real-world overall survival (rwOS) in the Flatiron Health cohort (nivolumab initiation until death or data cutoff). rwOS was compared with OS using unadjusted and adjusted Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was combined with the adjusted model to reduce baseline discrepancies., Results: The CheckMate 238 and real-world cohorts included 369 and 452 patients, respectively (median age, 56.0 and 63.0 years; median follow-up, 61.4 vs. 25.5 months). rwOS was not different from OS in the unadjusted (hazard ratio [HR] 1.27; 95% CI 0.92-1.74), adjusted (HR 1.01; 95% CI 0.67-1.54), and adjusted IPTW (HR 1.07; 95% CI 0.70-1.63) analyses. In the adjusted analysis, 2-year OS and rwOS rates were 84%. Median OS and rwOS were not reached. After IPTW, OS and rwOS were not different (HR 1.07; 95% CI 0.70-1.64)., Conclusions: In this comparative analysis, OS in the CheckMate 238 trial was similar to rwOS in the Flatiron Health database after adjustments in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab, validating the trial results., (© 2024. The Author(s).)

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., Competing Interests: Komal Gupte-Singh is an employee of Bristol Myers Squibb and holds stock/options in the company. Keith A. Betts, Ella Xiaoyan Du, and Xiaoyu Nie are employees of Analysis Group, Inc., which has received consulting fees from Bristol Myers Squibb. Scott D. Lee has served as a consultant for and/or received research support from Bristol Myers Squibb, Takeda, AbbVie, Janssen, Pfizer, Protagonist, AMT, and TLL Pharmaceutical. Timothy Ritter has nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Aim: Real-world adverse event (AE) data are limited for first-line (1L) treatments in advanced non-small-cell lung cancer (NSCLC). Methods: Using Flatiron Health Spotlight data, information for a pre-specified list of AEs was abstracted and described among patients with advanced NSCLC receiving 1L nivolumab + ipilimumab (NIVO + IPI), NIVO + IPI + chemotherapy and other approved immuno-oncology (IO) therapy + chemotherapy combination therapies. Results: Fatigue, pain, dyspnea, weight loss, decreased appetite, diarrhea, nausea/vomiting, cough, constipation and rash were the most common AEs. Rates of AEs were generally numerically similar across the three cohorts. The majority of patients received treatment for AEs and approximately one fourth of the patients had hospitalization due to their AEs. Conclusion: The real-world safety experiences of patients treated with 1L NIVO + IPI-based regimens were in general similar to those treated with other approved IO + chemotherapy combination therapies.

Aim: To compare the efficacy of erenumab versus rimegepant as preventive treatment for patients with episodic and chronic migraine using an anchor-based matching-adjusted indirect comparison. Methods: Patients from two phase II/III trials for erenumab (NCT02066415 and NCT02456740) were pooled and weighted to match on the baseline effect modifiers (age, sex, race, baseline monthly migraine days [MMDs], and history of chronic migraine [CM]) reported in the phase II/III trial for rimegepant (NCT03732638). Four efficacy outcomes were compared between the two erenumab regimens (70 mg and 140 mg) and rimegepant, including changes in MMDs from baseline to month 1 and month 3, changes in Migraine-Specific Quality of Life Questionnaire role function - restrictive domain score from baseline to month 3, and change in disability from baseline to Month 3. Results: Compared with rimegepant, erenumab 70 mg was associated with a statistically significant reduction in MMDs at month 3 (-0.90 [-1.76, -0.03]; p = 0.042) and erenumab 140 mg was associated with statistically significant reductions in MMDs at month 1 (-0.94 [-1.70, -0.19]; p = 0.014) and month 3 (-1.28 [-2.17, -0.40]; p = 0.005). The erenumab regimens also had numerical advantages over rimegepant for other efficacy outcomes. Conclusion: In the present study, we found that erenumab had a more favorable efficacy profile than rimegepant in reducing MMDs at month 1 and month 3 for migraine prevention. These results may help with decision-making in clinical practice and can be further validated in future clinical trials or real-world studies.

Introduction: Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib., Methods: MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022., Results: A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib., Conclusion: Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation., (© 2023. The Author(s).)

Objectives: This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy., Methods: A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective., Results: A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46)., Conclusions: VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy., Competing Interests: Author Disclosures Drs Li, Suh, and Lachaine reported receiving personal fees from AbbVie Inc during the conduct of the study. Drs Schuh and Pratz reported receiving grants and personal fees from AbbVie Inc during the conduct of the study. Drs Betts and Song reported receiving other from AbbVie Inc during the conduct of the study. Ms Dua reported receiving personal fees from AbbVie Inc during the conduct of the study. Dr Bui reported receiving personal fees and other from AbbVie Inc during the conduct of the study. No other disclosures were reported., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Nivolumab, a programmed cell death protein (PD)-1 inhibitor, was approved by the US Food and Drug Administration in 2021 advanced/metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, in combination with fluoropyrimidine and platinum-based chemotherapy. In the present study, the number needed to treat (NNT) for overall survival (OS), progression-free survival (PFS), and objective response rate (ORR)-and the number needed to harm (NNH) for tolerability outcomes-with nivolumab + chemotherapy versus chemotherapy alone were determined., Methods: NNT and NNH were calculated as the reciprocal of the risk difference between the two treatment arms, with the 95% CIs calculated as the reciprocals of the upper and lower bounds of the 95% CI of the risk difference, using data from the CheckMate 649 study., Findings: Among all treated patients, the NNTs for OS over 1 and 2 years were 15.15 and 12.05; for PFS, 10.87 and 19.61; and for ORR over the entire trial period, 8.95. The corresponding NNTs in the subgroup with PD-L1 CPS ≥5 were less. The NNH for grade ≥3 treatment-related adverse events (TEAEs) over 1 year among all treated patients was 7.02., Implications: The small estimated NNT values in this study suggest that patients would benefit from nivolumab + chemotherapy, and while the NNH for grade ≥3 TRAEs was small, the NNH for any individual TRAE were large or negative., Competing Interests: Declaration of Competing Interest K.A. Betts and X.Y. Nie are employees of Analysis Group Inc, which received consultant's fees from Bristol-Myers Squibb for this work. J. Hartman was an employee of, and holds stock options in, Bristol-Myers Squibb during the conduct of the study. H. Nguyen is an employee of, and holds stock options in, Bristol-Myers Squibb. The authors have indicated that they have no other conflicts of interest with regard to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

BACKGROUND: Immune checkpoint inhibitors, such as pembrolizumab, nivolumab, and atezolizumab, have demonstrated substantial survival benefits in patients with advanced non-small cell lung cancer (NSCLC). However, there is limited evidence on their relative safety profiles and adverse event (AE)-related cost burden. OBJECTIVE: To compare the AE management costs of nivolumab plus ipilimumab with and without limited chemotherapy with those of chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy in a first-line setting among patients with advanced NSCLC. METHODS: The mean per-patient AE costs were estimated using the incidence of all-cause grade 3/4 AEs with any-grade incidence greater than or equal to 15% and the corresponding costs of AE management in the inpatient setting. AE rates were obtained from individual patient data from the CheckMate 227 and CheckMate 9LA trials for nivolumab plus ipilimumab with/without limited chemotherapy and aggregated data from the KEYNOTE-189 and KEYNOTE-407 trials for pembrolizumab plus chemotherapy and the IMpower130 trial for atezolizumab plus chemotherapy. AE management costs from the third-party payer perspective were estimated based on inpatient medical costs from the 2016 United States Healthcare Cost and Utilization Project National Inpatient Sample. All costs were inflated to 2020 US dollars. RESULTS: Nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were associated with lower per-patient grade 3/4 AE costs compared with chemotherapy ($1,708 and $624 lower over the treatment course, respectively). Compared with pembrolizumab plus chemotherapy, nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs in patients with nonsquamous histology (difference: -$4,866) and squamous histology (difference: -$3,795), and nivolumab plus ipilimumab with limited chemotherapy also had lower AE costs for both nonsquamous (difference: -$2,800) and squamous (difference: -$2,753) disease. Similarly, nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were also associated with lower AE costs ($11,400 and $8,809 lower, respectively) compared with atezolizumab plus chemotherapy among patients with nonsquamous disease. In particular, nivolumab plus ipilimumab without or with limited chemotherapy were associated with much lower AE costs of hematological AEs compared with chemotherapy and other immune checkpoint inhibitor-based treatments in combination with a full course of chemotherapy. CONCLUSIONS: Nivolumab plus ipilimumab with/without limited chemotherapy was associated with lower AE management costs compared with chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy as first-line treatment for advanced NSCLC. The AE cost benefits were largely driven by the lower cost burden for hematological AEs for nivolumab plus ipilimumab with/without limited chemotherapy. DISCLOSURES This study was supported by Bristol-Myers Squibb. The sponsor was involved in all aspects of the work and in the decision to submit the manuscript for publication. Dr Stenehjem has received consulting fees from Bristol-Myers Squibb. Dr Lubinga was an employee of Bristol-Myers Squibb at the time of the study's conduct and holds stock/options. Drs Betts and Wu are employees of Analysis Group, Inc., a consulting company that has received funding from Bristol-Myers Squibb for this research.

Background: Benralizumab is an mAb therapy for severe eosinophilic asthma. Real-world data on its clinical impact in various patient populations such as patients with varying eosinophil levels, previous biologic use, and extended follow-up in the United States are limited., Objective: To determine the effectiveness of benralizumab in different asthmatic patient cohorts and its long-term clinical impact., Methods: Patients with asthma treated with benralizumab from November 2017 to June 2019 with 2 or more exacerbations in the 12 months before benralizumab initiation (index) were included in this pre-post cohort study that used medical, laboratory, and pharmacy US insurance claims. Asthma exacerbation rates in the 12 months pre and post index were compared. Nonmutually exclusive patient cohorts were defined by blood eosinophil counts (<150, ≥150, 150-<300, <300, and ≥300 cells/μL), a switch from another biologic, or follow-up for 18 or 24 months post index., Results: There were 429 patients in the eosinophil cohort, 349 in the biologic-experienced cohort, and 419 in the extended follow-up cohort. In all eosinophil cohort subgroups, the asthma exacerbation rate decreased from 3.10-3.55 per patient-year (PPY) pre index to 1.11-1.72 PPY post index (52%-64% decrease; P < .001). Similar decreases were observed in patients switching from omalizumab (3.25 to 1.25 PPY [62%]) or mepolizumab (3.81 to 1.78 PPY [53%]) to benralizumab and those followed up for 18 months (3.38 to 1.18 PPY [65%]) or 24 months (3.38 to 1.08 PPY [68%]) (all P < .001). In the extended follow-up cohort, 39% and 49% had no exacerbations in the 0 to 12 months and the 12 to 24 months post index, respectively., Conclusions: Benralizumab achieved significantly improved asthma control in real-world patients with different blood eosinophil counts, including eosinophil counts ranging from less than 150 to greater than or equal to 300 cells/μL, switching from other biologics, or treated for up to 24 months., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials., Objective: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib., Design, Setting, and Participants: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426., Intervention: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially)., Outcome Measurements and Statistical Analysis: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib., Results and Limitations: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted., Conclusions: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC., Patient Summary: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions., (Copyright © 2023. Published by Elsevier B.V.)

Background: Recurrence-free survival (RFS) and overall survival (OS) data for adjuvant nivolumab versus placebo (proxy for routine surveillance) in patients with high-risk, resected melanoma are lacking. This post hoc, indirect treatment comparison (ITC) used pooled data from the phase 3 EORTC 18,071 (ipilimumab vs. placebo) and CheckMate 238 (nivolumab vs. ipilimumab) trials to assess RFS and OS with nivolumab versus placebo and the numbers needed to treat (NNT) over 4 years., Methods: Patients with resected stage IIIB-C cutaneous melanoma (American Joint Committee on Cancer seventh edition) were included. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics. RFS NNTs were calculated for nivolumab versus ipilimumab and placebo. OS NNTs were calculated for nivolumab versus placebo. To adjust for different post-recurrence treatments, the difference in post-recurrence survival between the two ipilimumab arms was added to OS of the placebo arm., Results: This ITC included 278, 643, and 365 patients treated with nivolumab, ipilimumab, and placebo, respectively. Following IPTW, nivolumab was associated with improved RFS versus placebo (hazard ratio [HR]: 0.49; 95% confidence interval [CI] 0.39-0.61) and ipilimumab (HR: 0.69; 95% CI 0.56-0.85). RFS NNT was 4.2 for nivolumab versus placebo and 8.9 for nivolumab versus ipilimumab. After post-recurrence survival adjustment, weighted 4-year OS rates were 75.8% for nivolumab and 64.1% for placebo; OS NNT for nivolumab versus placebo was 8.5., Conclusions: In patients with resected stage IIIB-C cutaneous melanoma in this ITC, nivolumab improved RFS versus placebo and ipilimumab, and OS versus placebo after post-recurrence survival adjustment., (© 2022. The Author(s).)

Background: Hyperkalemia is associated with increased healthcare resource utilization (HRU). This study evaluated the impact of sodium zirconium cyclosilicate (SZC) use on HRU in outpatients with hyperkalemia., Research Design and Methods: A retrospective noncomparative study using claims data from the HealthVerity warehouse, which included outpatients in the United States who initiated SZC between January and December 2019 (index date) with ≥6 months' continuous coverage before (baseline) and after (follow-up) the index date (total coverage of 12 months). The study aimed to describe HRU with long-term and short-term SZC (defined as >90 and ≤90 days' supply, respectively, during 180 days' follow-up) and identify characteristics associated with long-term versus short-term therapy., Results: Of 1153 patients, 748 (64.9%) received short-term and 405 (35.1%) received long-term therapy. During follow-up, lower proportions of patients on long-term versus short-term therapy had hyperkalemia-related hospitalizations (10.1% vs 15.1%; P < 0.05) and all-cause hospitalizations (22.5% vs 29.3%; P < 0.05). Hyperkalemia-related and all-cause hospitalization proportions were 33.0% and 23.3% lower, respectively. Predictors of long-term therapy included stage 3 chronic kidney disease., Conclusions: Approximately one-third of patients with hyperkalemia received long-term SZC therapy. Hyperkalemia-related and all-cause hospitalization proportions were lower with long-term therapy, although further confirmatory studies are needed.

Background: Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking., Materials and Methods: A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars., Results: Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs. $4508 vs. $5772, and treatment-related grade 3/4 AE costs were $741 vs. $2722 vs. $4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs. $5800 vs. $9285, while treatment-related grade 3/4 AE costs were $863 vs. $3162 vs. $5030 over ~26.6 months of FU., Conclusion: Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile., (© The Author(s) 2022. Published by Oxford University Press.)

Background and Aim: Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US., Methods: Insurance claims data (11/2016-6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months)., Results: In all cohorts (mean age 51-53 years; 67-70% female; biologic-naïve, N  = 1,292; biologic-experienced, N  = 349; 18-month follow-up, N  = 419; 24-month follow-up, N  = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53-68% ( p  < .001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p  < .001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p  < .001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort., Conclusion: Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation.

Objective: To assess the available clinical and economic evidence of erenumab vs onabotulinumtoxinA for chronic migraine (CM) and present de-novo indirect treatment comparisons (ITCs) based on available clinical trial data., Methods: We conducted ITCs based on results from the pivotal 295 trial (NCT02066415) of erenumab vs placebo and published aggregate data from the PREEMPT 1 (NCT00156910) and PREEMPT 2 (NCT00168428) trials of onabotulinumtoxinA vs placebo. ITCs were conducted for CM patients with and without prior administration of onabotulinumtoxinA and among CM patients with ≥3 prior preventive treatment failures. Efficacy was assessed based on responder rates of ≥50% reductions in monthly headache days (MHDs) and monthly migraine days (MMDs) as well as change from baseline in both MHDs and MMDs., Results: Among patients with CM, 140 mg erenumab was associated with a reduction of 1.2 MHD ( p  = .092) and a reduction of 1.0 MMD ( p  = .174) compared to onabotulinumtoxinA at Week 12. Among onabotulinumtoxinA-naïve patients, erenumab was associated with a reduction of 1.8 MHD ( p  = .026) and 1.4 MMD ( p  = .080) at Week 12. Among patients that had received ≥3 prior preventive treatments, the odds ratios comparing erenumab vs onabotulinumtoxinA were 1.7 for ≥50% responder rates based on reductions in MHD ( p  = .155) and 1.7 for ≥50% responder rates based on reductions in MMD ( p  = .140)., Conclusion: These findings suggest directional benefits (although not reaching the threshold of statistical significance) associated with erenumab vs onabotulinumtoxinA for the preventive treatment of CM. Evidence from this study may inform healthcare stakeholders in treatment selection and optimization for patients with CM.

BACKGROUND: Venetoclax, in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC), received confirmatory approval in 2020 by the US Food and Drug Administration for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients aged 75 years or older or who are ineligible for intensive induction chemotherapy. The economic value associated with response to venetoclax combinations compared with other treatments for this patient population has not been comprehensively evaluated. OBJECTIVE: To assess the cost per patient achieving remission with venetoclax combination therapies, compared with other therapies for newly diagnosed patients with AML who are ineligible for intensive induction chemotherapy, from a US third-party payer perspective. METHODS: The analysis used treatment effect estimates (ie, complete remission [CR] + CR with incomplete blood count recovery [CRi]) from a network meta-analysis and annual cost estimates from a prior budget impact model. The model considered the total cost of care including the costs of drug and administration, adverse events, hospitalization, disease monitoring, blood transfusions, and subsequent AML management when patients discontinued active treatment. Costs per patient achieving CR + CRi associated with venetoclax + azacitidine, venetoclax + LDAC, azacitidine, decitabine, LDAC, and best supportive care (ie, treatment given with the intent to maximize quality of life without specific antileukemic intent, such as blood transfusion products and antibiotics) were calculated as the annual total cost of care per patient divided by the CR + CRi rate. All costs were adjusted to 2020 US dollars. RESULTS: Venetoclax combination therapies were estimated to have substantially lower costs per patient achieving CR + CRi (venetoclax + azacitidine: $473,960; venetoclax + LDAC: $428,071) than alternative treatments. Azacitidine was estimated to have the the highest cost per patient achieving CR + CRi ($1,197,438), followed by best supportive care ($869,849), LDAC ($689,101), and decitabine ($594,074). A pair-wise matrix of the difference between therapies estimated that both venetoclax + azacitidine and venetoclax + LDAC were associated with significantly lower costs per patient achieving CR + CRi than azacitidine (by $723,477 and $769,367, respectively) and LDAC (by $215,141 and $261,030; all P < 0.05). CONCLUSIONS: From a US third-party payer perspective, venetoclax in combination with azacitidine or LDAC was estimated to be associated with a significantly lower cost per patient achieving CR + CRi than azacitidine or LDAC among newly diagnosed patients with AML ineligible for intensive chemotherapy. DISCLOSURES: This research was supported by AbbVie Inc. and Genentech. The sponsors helped design the study, interpret the data, and draft the manuscript. Drs Bui and Kapustyan are employees of and have equity ownership in AbbVie; Dr Choi was an employee of AbbVie during the study's conduct and has equity ownership. Ms Ma and Dr Montez are employees of and have equity ownership in Genentech. Drs Song and Chai, Ms Yin, and Dr Betts are employees of Analysis Group, Inc., which has received funding from AbbVie and Genentech for the conduct of this research. Dr LeBlanc reports personal fees for consulting or advisory boards from AbbVie, Agios/Servier, AstraZeneca, Amgen, Astellas, BlueNote, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Genentech, GSK, Pfizer, and Seattle Genetics; royalties from UpToDate; speakers bureau fees from Agios/Servier, AbbVie, and BMS/Celgene; and grants and/or research contracts from the American Cancer Society, AstraZeneca, BMS, Jazz Pharmaceuticals, and Seattle Genetics.

Rationale & Objective: To evaluate progression patterns and associated economic outcomes, using estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) based on the Kidney Disease: Improving Global Outcomes (KDIGO) risk categories, among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD)., Study Design: Patients with T2D and moderate- or high-risk CKD were selected from the Optum electronic health records database (January 2007-December 2019). Progression patterns and post-progression economic outcomes were assessed., Setting & Participants: Adults with T2D and CKD in clinical settings., Predictor: Baseline KDIGO risk categories., Outcomes: Progression to a more severe KDIGO risk category; healthcare resource utilization and medical costs., Analytical Approach: Progression probability was estimated using cumulative incidence. Healthcare resource utilization and costs were compared across progression groups., Results: Of 269,187 patients (mean age 65.6 years) with T2D and CKD of moderate or high baseline risk, 18.9% progressed to the very high-risk category within 5 years. Among moderate-risk patients, 17.8% of CKD stage G1-A2, 44.0% of stage G2-A2, and 61.3% of stage G3a-A1 patients progressed to a higher KDIGO risk category. Among high-risk patients, 63.9% of stage G3b-A1/G3a-A2 and 56.0% of stage G2-A3 patients progressed to very high risk. Within the same eGFR stage, a higher UACR stage was associated with 4- to 7-times higher risk of progressing to very high risk and faster eGFR decline. Nonprogressors had lower annual medical costs ($16,924) than patients who progressed from moderate risk to high risk ($22,117, P  < 0.05), from high risk to very high risk ($32,204, P  < 0.05), and from moderate risk to very high risk ($35,092, P  < 0.05)., Limitations: Infrequent lab testing might have caused lags in identifying progression; medical costs were calculated using unit costs., Conclusions: Patients with T2D and CKD of moderate or high risk per KDIGO risk categories had high probabilities of progression, incurring a substantial economic burden. The results highlight the value of UACR in CKD management., (© 2022 The Authors.)

Introduction: Eosinophilic gastritis and eosinophilic enteritis (EoG/EoN) are associated with a substantial clinical burden. However, limited information is available regarding the economic burden of EoG/EoN. This study was conducted to compare healthcare resource use (HRU) and costs among patients with EoG/EoN versus without EoG/EoN in the USA., Methods: Administrative claims data from the IBM MarketScan ® Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits Databases (2009-2019) was used to identify two cohorts of patients. Patients without EoG/EoN were matched 3:1 to patients with EoG/EoN on sex, year of birth, and healthcare plan type. Study measures included demographic characteristics, select comorbidities, all-cause HRU, and costs. Comparisons were made over a 1-year period following EoG/EoN diagnosis for patients with EoG/EoN and an eligible date for patients without EoG/EoN., Results: A total of 2219 patients with EoG/EoN and 6657 patients without EoG/EoN were analyzed. Significantly higher proportions of patients with EoG/EoN versus without EoG/EoN had comorbid conditions. Rates of all-cause HRU were significantly higher among patients with EoG/EoN versus patients without EoG/EoN (adjusted rate ratio [95% confidence interval]: inpatient visits, 6.26 [5.26, 7.46]; outpatient visits, 1.17 [1.16, 1.19]; emergency department visits, 2.11 [1.98, 2.25]; all p < 0.001). Patients with EoG/EoN incurred significantly higher costs versus patients without EoG/EoN (adjusted mean cost difference $31,180; p < 0.001). Cost differences were largely due to outpatient (adjusted mean cost difference $14,018; p < 0.001) and inpatient (adjusted mean cost difference $11,224; p < 0.001) costs., Conclusion: The economic burden associated with EoG/EoN is substantial, with patients with EoG/EoN having a higher rate of HRU and incurring $31,180 more than patients without EoG/EoN on average. Most of the cost difference was attributable to outpatient and inpatient costs. Cost-saving strategies to lower the burden of illness in this patient population are needed., (© 2022. The Author(s).)

Objectives: Clinical practice guidelines recommend at least annual testing of estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (uACR) for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). This study assessed the adequacy of eGFR and uACR testing in this patient population across the United States., Study Design: Observational real-world study., Methods: Adults with CKD and T2D were identified from the Optum Clinformatics database (2015-2019). The eGFR and uACR tests were assessed nationally and by state. The proportions of tested patients and patients receiving adequate monitoring per clinical practice guidelines were analyzed during the 1-year period after T2D and CKD diagnosis, along with all-cause health care costs., Results: Among 101,057 adults with CKD and T2D, 94.1% had at least 1 eGFR test and 38.7% had at least 1 uACR test over 1 year. Only 20.3% of patients had adequate uACR monitoring; this was much lower than observed for adequate eGFR monitoring (86.6%). The eGFR testing rates were high across states (range, 79.5% [Colorado] to 97.3% [Alabama]); conversely, uACR testing rates were uniformly lower and showed wider variation (range, 14.0% [Maine] to 58.9% [Hawaii]). Mean annual all-cause health care costs were $28,636 and increased with CKD GFR stage. Lower uACR testing rates were associated with higher health care costs at the state level (Pearson r = -0.55; P < .01)., Conclusions: In the United States, uACR testing is underutilized, with large geographical variations in testing rates noted between states. Lower uACR testing rates were associated with higher health care costs. The lack of sufficient uACR testing raises concerns about CKD management in patients with T2D.

Background and Objectives: Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC., Methods: Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms., Results: Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs., Conclusions: Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period., (© 2022. The Author(s).)

Background: Real-world evidence characterizing the clinical outcomes and economic impact on patients with severe eosinophilic asthma treated with benralizumab is limited., Objective: To characterize patients with severe asthma treated with benralizumab and assess its clinical and economic impact in the United States., Methods: A pre-post benralizumab comparison was performed using a large US insurance claims database between November 2016 and November 2019. The primary cohort included patients with asthma aged 12 years or more with 2 or more records of benralizumab. Secondary cohorts included persistent users (6 or more records of benralizumab), patients switching to benralizumab from mepolizumab or omalizumab, and stratified by Medicaid vs non-Medicaid. Exacerbations, concomitant medications, and exacerbation-related health care resource utilization (HCRU) and costs were compared in the 12-month periods pre- and post-benralizumab initiation (index)., Results: Of the 204 patients in the primary cohort, mean age at index was 45.3 years and 68.6% were of female sex. The patients experienced a significant 55% reduction in rates of exacerbations post-benralizumab initiation (3.25 pre-index vs 1.47 post-index per person-year; P < .001), and 41% of the patients had no exacerbations post-benralizumab initiation. The proportion of oral corticosteroid-dependent patients decreased from 82% to 50% (P < .001). Reductions in HCRU were 42%, 46%, and 57% for asthma exacerbation-related inpatient hospitalizations, emergency department, and outpatient visits, respectively (all P < .001). Exacerbation-related costs decreased by $6439 ($13,559 vs $7120; P < .001). Similar results for all outcomes were observed for the persistent cohort, switch cohorts, and Medicaid vs non-Medicaid cohorts., Conclusion: Patients with severe asthma treated with benralizumab experienced clinical and economic benefits in the real world, as demonstrated by the reduction in exacerbations and HCRU., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (nivolumab plus ipilimumab, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received nivolumab plus ipilimumab had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs than sunitinib.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA)., Methods: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles., Results: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA., Conclusion: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster)., (© 2021. The Author(s).)

Introduction: Hyperkalemia is often managed in the emergency department (ED) and it is important to understand how ED management and post-discharge outcomes vary by hyperkalemia severity. This study was conducted to characterize ED management and post-discharge outcomes across hyperkalemia severities., Methods: Adults with an ED visit with hyperkalemia (at least one serum potassium lab measure above 5.0 mEq/L) were selected from US electronic medical record data (2012-2018). Patient characteristics, potassium levels, treatments, and monitoring prior to and during the ED visit were compared by hyperkalemia severity (mild [> 5.0-5.5 mEq/L], moderate [> 5.5-6.0], severe [> 6.0]) using unadjusted analyses. Death, immediate inpatient admission, 30-day hyperkalemia recurrence, and 30-day inpatient admission were also assessed by severity., Results: Of 6222 patients included, 4432 (71.2%) had mild hyperkalemia, 1085 (17.4%) had moderate, and 705 (11.3%) had severe hyperkalemia. Chronic kidney disease (39.9-50.1%) and heart failure (21.6-24.3%) were common. In the ED, electrocardiograms (mild, 56.5%; moderate, 69.6%; severe, 81.0%) and patients with at least two potassium laboratory values increased with severity (15.0%; 40.4%; 75.5%). Among patients with at least two potassium laboratory values, over half of patients (60.4%) had potassium levels ≤ 5.0 mEq/L prior to discharge. Use of potassium-binding treatments (sodium polystyrene sulfonate: mild = 4.1%; moderate = 17.1%; severe = 27.4%), temporizing agents (5.6%; 15.5%; 31.6%), or dialysis (0.4%; 0.8%; 3.0%) increased with severity; treatment at discharge was not common. Death (1.1%; 3.7%; 10.6%), immediate admission to inpatient care (5.8%; 8.7%; 12.7%), 30-day hyperkalemia recurrence (2.9%; 19.0%; 32.5%), 30-day inpatient admission with hyperkalemia (6.5%; 7.9%; 9.3%) also increased with severity., Conclusion: Patients with moderate and severe hyperkalemia experienced elevated risk of hyperkalemia recurrence and hyperkalemia-related inpatient readmission following discharge from the ED from a descriptive analysis. Future research to assess strategies to reduce hyperkalemia recurrence and inpatient admission in this patient population would be beneficial., (© 2021. The Author(s).)

The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization. As such, a literature review was conducted to better understand the economic value of remission. Despite the large heterogeneity found in RA-related economic outcomes across studies, patients in remission consistently had lower direct medical and indirect costs, less healthcare resource utilization, and greater productivity compared to those without remission. Remission was associated with 19-52% savings in direct medical costs and 37-75% savings in indirect costs. The economic value of remission should thus be considered in economic analyses of RA therapies to inform treatment and reimbursement decisions., (© 2021. The Author(s).)

Introduction: The long-term benefit-risk profiles of licensed and investigational treatments for moderate-to-severe plaque psoriasis have not been fully characterized., Methods: Randomized controlled trials (RCTs) of licensed and investigational treatments for moderate-to-severe plaque psoriasis were identified through a systematic literature review through 2 May 2021. Bayesian network meta-analyses (NMAs) were conducted to compare the efficacy (Psoriasis Area and Severity Index [PASI] 75/90/100 [at least a 75/90/100% reduction in PASI score from baseline] response) and safety outcomes (any adverse event [AE], any serious AE [SAE], and AEs leading to treatment discontinuation) of each treatment evaluated between weeks 48 and 56 after baseline. Surfaces under the cumulative ranking curves (SUCRAs) were calculated to evaluate the relative ranking of treatments. The benefit-risk profiles of treatments were assessed by bidimensional plots of the NMA-estimated efficacy and safety outcomes., Results: In the efficacy NMA (N = 14 RCTs), the relative rankings for PASI 75/90/100 responses by weeks 48-56 were the highest for risankizumab (SUCRA: 98.5%) and bimekizumab (83.8% for dosing every 4 weeks [Q4W], 72.7% for dosing Q4W then every 8 weeks). The PASI response rates did not differ significantly between risankizumab and the two bimekizumab regimens. Additionally, risankizumab was associated with significantly higher PASI response rates than brodalumab, guselkumab, ixekizumab, secukinumab, ustekinumab, adalimumab, and etanercept. In the safety NMAs (N = 8 RCTs), risankizumab had the highest relative rankings for all three outcomes (SUCRA: 92.1%, 82.0%, and 91.0% for any AE, any SAE, and AEs leading to treatment discontinuation, respectively). Risankizumab had a significantly lower rate of any AE than bimekizumab, ustekinumab, and secukinumab., Conclusions: Risankizumab was associated with the most favorable long-term benefit-risk profile for the treatment of moderate-to-severe plaque psoriasis. Although ixekizumab and bimekizumab had favorable efficacy profiles, both treatments had lower rankings for safety outcomes., (© 2021. The Author(s).)

Objective: To provide cost estimates for chronic kidney disease (CKD) management and major CKD complications among patients with CKD and type 2 diabetes (T2D)., Study Design: A retrospective cohort study of 52,599 adults with CKD and T2D using Optum Clinformatics claims data from 2014 to 2019., Methods: Medical costs associated with CKD management, renal replacement therapies (RRTs), major CKD complications (eg, myocardial infarction, stroke, heart failure, atrial fibrillation, and hyperkalemia), and death were estimated using generalized estimating equations adjusting for baseline demographics, complications, and medical costs. Costs for CKD management, RRT, and major CKD complications were assessed in 4-month cycles. Mortality costs were assessed in the month before death., Results: The estimated 4-month CKD management costs ranged from $7725 for stage I to II disease to $11,879 for stage V (without RRT), with high additional costs for dialysis and kidney transplantation ($87,538 and $124,271, respectively). The acute event costs were $31,063 for heart failure, $21,087 for stroke, and $21,016 for myocardial infarction in the first 4 months after the incident event, which all decreased substantially in subsequent 4-month cycles. The acute event costs of atrial fibrillation and hyperkalemia were $30,500 and $31,212 with hospitalization, and $5162 and $1782 without. The costs associated with cardiovascular-related death, renal-related death, and death from other causes were $17,031, $12,605, and $9900, respectively., Conclusions: Management of CKD and its complications incurs high medical costs for patients with CKD and T2D. Results from this study can be used to quantify the economic profile of emerging treatments and inform decision-making.

Introduction: The progression of mild hyperkalemia and the predictors of progression have not been well characterized. In this study we aimed to characterize the progression of hyperkalemia and identify the risk factors for hyperkalemia progression., Methods: Adults with mild hyperkalemia (at least one serum potassium measure > 5.0 and ≤ 5.5 mEq/L) were identified using electronic medical records from the Research Action for Health Network (2012-2018). Progression to moderate-to-severe and progression to severe hyperkalemia were defined as the first occurrences of a serum potassium measure > 5.5 and > 6.0 mEq/L, respectively. Kaplan-Meier analyses were conducted to estimate progression rates for all patients and by pre-specified patient subgroups. Hazard ratios (HR) of moderate-to-severe and severe hyperkalemia progression were estimated using Cox models., Results: Of 35,369 patients with mild hyperkalemia, 16.9% and 8.7% progressed to moderate-to-severe and severe hyperkalemia, respectively. Rates of hyperkalemia progression elevated with the severity of chronic kidney disease (CKD). The highest progression rates were seen in patients with CKD stage 5 (stage 5 vs. no CKD: moderate-to-severe, 50.2% vs. 12.0%; severe, 31.3% vs. 3.9%; p < 0.001). Higher progression rates were also observed in patients with heart failure, hypertension, and type II diabetes compared with patients without those conditions (all p < 0.001). The most prominent risk factors were CKD stage 5 (HR of progression to moderate-to-severe hyperkalemia, 3.32 [95% CI 3.03-3.64]; severe, 4.08 [3.55-4.69]), CKD stage 4 (2.19 [1.97-2.43], 2.28 [1.92-2.71]), CKD stage 3 (1.57 [1.46-1.68], 1.65 [1.46-1.87]), type I diabetes (1.37 [1.18-1.61], 1.54 [1.23-1.93]), and serum potassium (1.12 [1.10-1.15], 1.13 [1.10-1.17] per 0.1 mEq/L increase) (all p values < 0.05)., Conclusion: Hyperkalemia progression rates increased significantly with CKD stage and were also higher among patients with higher baseline potassium level, heart failure, hypertension, and diabetes., (© 2021. The Author(s).)

Introduction: Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence., Methods: Adult patients with CKD stage 3-5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate < 18 mEq/l and < 22 mEq/l)., Results: In the 2017 patient cohort and among patients with CKD and hyperkalemia, patients with metabolic acidosis were younger (69 versus 74 years), more likely to have advanced CKD (35% versus 13%), and use oral sodium bicarbonate (21% versus 4%) than patients without metabolic acidosis. The prevalence of metabolic acidosis (< 22 mEq/l) ranged from 25 to 29% when hyperkalemia was defined by potassium > 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l., Conclusion: Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized., (© 2021. The Author(s).)

Objectives: Patients with hyperkalemia are commonly treated in the inpatient setting; however, real-world evidence is limited. The purpose of this study was to describe the inpatient management and post-discharge outcomes among patients with hyperkalemia., Methods: Electronic medical record data (2012-2018) were used to analyze US adult patients with an inpatient stay with hyperkalemia (≥1 potassium value >5.0mEq/L). Patient characteristics, treatments, and monitoring six months prior to and during the inpatient stay, and hyperkalemia recurrence and inpatient readmissions post-discharge were summarized and compared among patients with mild (>5.0-5.5mEq/L), moderate (>5.5-6.0), and severe (>6.0) hyperkalemia., Results: Of the 21,793 patients, 69.2% had mild, 19.0% had moderate, and 11.8% had severe hyperkalemia during inpatient care. The most common inpatient treatments were temporizing agents (mild: 28.9%; moderate: 46.0%; severe: 73.0%), diuretics (32.7%; 37.1%; 34.6%), and sodium-polystyrene sulfonate (11.7%; 27.8%; 45.3%). Almost no patients (0.1%) received a potassium binder at discharge. Most patients (86.8%) had their potassium levels return to ≤5.0mEq/L during the inpatient stay. Death during the inpatient stay occurred in 12.3% of mild, 15.5% of moderate, and 19.5% of severe hyperkalemic patients. Within 30 days of discharge, hyperkalemia recurred in 13.3%, 15.4%, and 18.4% of patients with mild, moderate, and severe hyperkalemia, respectively. Additionally, 19.7%, 21.5%, and 19.6% of patients were readmitted to inpatient care within 30 days post-discharge., Conclusion: Among patients with hyperkalemia in the inpatient setting, treatment and normalization of serum potassium levels were common. However, death, readmission, and hyperkalemia recurrence were also fairly common across all cohorts. Future studies examining measures to reduce inpatient death, readmission, and hyperkalemia recurrence among patients with hyperkalemia in inpatient care are warranted.

Background: The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied., Objective: To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments., Methods: A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs)., Results: Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile., Limitations: The results may not be generalizable to real-world populations., Conclusions: Anti-interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term., Competing Interests: Conflicts of interest Dr Shear is a paid consultant for AbbVie, Amgen, Lilly, Leo, Bausch Health, Sun Pharma, Janssen, Galderma, Otsuka, UCB, Celgene, Sanofi Genzyme, Novartis, and Pfizer. Drs Joshi, Soliman, and Sinvhal are employees of AbbVie and may own AbbVie stock or stock options. Drs Betts, Wang, and Zhao are employees of Analysis Group, Inc, which received payment from AbbVie Inc for participation in this research. Dr Gisondi has served as a speaker or an advisory board member for AbbVie, Almirall, Amgen, BMS, Celgene, Eli-Lilly, Janssen, Leo-pharma, Merck, MSD, Novartis, Pfizer, Sanofi, Sandoz, and UCB Pharma. Dr Armstrong has served as a research investigator or consultant to Leo, AbbVie, UCB, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun, Dermavant, BMS, Sanofi, Regeneron, Dermira, and Modmed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Chemotherapy (CT) alone was previously standard first-line (1L) therapy for metastatic non-small-cell lung cancer (NSCLC) but alternative treatments, including immunotherapy (I-O), are now available. Patients & methods: In this retrospective study, adults with stage IV NSCLC who initiated 1L treatment between 1 August 2018 and 31 December 2019 and had ≥2 visits were identified in the Flatiron database. Patients were followed up until 30 June 2020. Baseline characteristics and treatment patterns were described by treatment group: CT, I-O + CT, I-O monotherapy and other. Results: Approximately 20% of patients received 1L CT in the 2018-2019 timeframe studied; these patients tended to have squamous histology and low (≤49%) programmed death ligand-1 expression. Conclusion: A proportion of patients with metastatic NSCLC still receive 1L CT despite the availability and widespread use of I-O therapies.

While results from clinical trials are important in determining the efficacy of treatment, restrictive eligibility criteria may limit generalizability to patient populations in the real-world setting. Real-world analyses can therefore identify subgroups of patients who may respond differently to specific therapeutic regimens. This supplementary data is supportive to the research article entitled "Real-world outcomes of immunotherapy-based regimens in first-line advanced non-small cell lung cancer" [1]. Using electronic health records data from a large demographically and geographically diverse oncology database, we present real-world progression-free survival (rwPFS) outcomes for patients with advanced non-small cell lung cancer in the United States treated with either first-line immunotherapy as monotherapy or single-agent immunotherapy combined with chemotherapy. rwPFS was estimated for patients in each treatment group using Kaplan-Meier methods; analyses were conducted separately for patients with squamous and non-squamous histology and stratified by Eastern Cooperative Oncology Group performance status, tumor programmed death ligand-1 expression, and presence of brain metastases., Competing Interests: Keith Betts, Sophie Gao and Lei Yin are employees of Analysis Group which received research funding for the work under consideration. David Stenehjem has received personal fees from Bristol Myers Squibb, Dracen Pharmaceuticals, Iterion Therapeutics, Molecular Templates, and Salarius Pharmaceuticals; grants from Bristol Myers Squibb, AstraZeneca, Bayer, Novartis, and Jazz Pharmaceuticals. David Waterhouse has received personal fees from Abbvie, Amgen, AstraZeneca, AZTherapies, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Janssen Oncology, Jazz Pharmaceuticals, MCGivenny Global, Merck, Pfizer, Mirati Therapeutics, and Seattle Genetics. John Hartman, Jenny Lam, Solomon Lubinga and Sumati Rao are employees of Bristol Myers Squibb., (© 2021 Bristol Myers Squibb. Published by Elsevier Inc.)

Background: First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States., Methods: Patients aged ≥18 years with confirmed advanced (stage III-IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020., Results: Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3-11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3-12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8-12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4-15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort., Conclusion: Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O-based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens., (Copyright © 2021 Bristol Myers Squibb. Published by Elsevier B.V. All rights reserved.)

Introduction: The clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis., Methods: A systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration- or European Medicines Agency-licensed treatments for moderate-to-severe psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10-16 weeks from baseline) and maintenance periods (long-term: 48-52 weeks from baseline) were estimated using Bayesian network meta-analysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments., Results: In the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.9%, SUCRA 0.951), risankizumab (72.5%, 0.940), and brodalumab (72.0%, 0.930), which were significantly higher than those for guselkumab (65.0%, 0.795), secukinumab (65.0%, 0.794), infliximab (56.8%, 0.702), certolizumab (400 mg: 49.6%, 0.607; 200 mg: 42.2%, 0.389), ustekinumab (90 mg: 47.9%, 0.568; weight-based: 45.7%, 0.505; 45 mg: 44.6%, 0.460), adalimumab (43.0%, 0.410), tildrakizumab (200 mg: 39.7%, 0.327; 100 mg: 37.2%, 0.268), etanercept (18.0%, 0.171), apremilast (12.4%, 0.090), and dimethyl fumarate (12.2%, 0.092). The PASI 100 response rates were highest for ixekizumab (41.4%), risankizumab (40.8%), and brodalumab (40.3%). In the long term (N = 11 RCTs), the PASI 90 rate was highest for risankizumab (85.3%, SUCRA: 0.998), which were significantly higher than those for brodalumab (78.8%, 0.786), guselkumab (78.1%, 0.760), ixekizumab (72.1%, 0.577), secukinumab (67.0%, 0.450), ustekinumab (weight-based: 55.0%, 0.252), adalimumab (51.6%, 0.176), and etanercept (37.9%, 0.001). Risankizumab had the highest PASI 100 response rate (65.4%), followed by brodalumab (55.7%) and guselkumab (54.8%)., Conclusions: Ixekizumab, risankizumab, and brodalumab had the highest short-term efficacy, and risankizumab had the highest long-term efficacy.

Introduction: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers., Methods: A retrospective chart review of patients with migraine treated with erenumab for at least 3 months across five major headache centers was conducted. Data was collected from patient charts between April 2019 and April 2020 and included patient and clinical characteristics, migraine medication use, and outpatient visits. The date of the first prescription fill of erenumab was defined as the index date. The baseline period comprised the 3 months prior to the index date and the study period comprised the at least 3 months on erenumab treatment., Results: Data from a total of 1034 patients with chronic migraine with a mean of 9.3 months of erenumab treatment were analyzed. Patients were on average 48 years old, 86% were female, and 79% were white. Patients had a mean of 5 preventive treatment failures prior to erenumab initiation. Patients used a mean of 2 preventive treatments (excluding erenumab) and 2 acute treatments during baseline and study periods. Among patients with effectiveness data, 45% of patients had improvement in physician-reported migraine severity and 35% experienced at least 50% reduction in mean headache/migraine days per month. The average number of monthly outpatient visits was 0.43 and 0.30 before and after erenumab initiation, respectively., Conclusion: In this predominantly refractory chronic migraine population treated in select headache centers, patients had fewer headache/migraine days per month and outpatient visits after initiating erenumab. However, patients largely continued to be managed via a polypharmacy approach after erenumab initiation.

Aims: To compare the efficacy of nivolumab 1 mg/kg + ipilimumab 3 mg/kg with regorafenib 160 mg, cabozantinib 60 mg and nivolumab 3 mg/kg monotherapy for second-line treatment of advanced hepatocellular carcinoma. Materials & methods: Indirect comparison using network meta-analysis and propensity score weighting. Results:  Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had significantly higher objective response rate (median 31.2% [95% credible interval: 19.6-44.5%]) than cabozantinib (4.2% [2.0-6.5%]) and regorafenib (4.8% [1.1-8.3%]), and significantly longer overall survival (cabozantinib: hazard ratio: 0.46 [95% credible interval: 0.27-0.79]; regorafenib: 0.56 [0.32-0.97]). Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had significantly better objective response rate (difference 21.0% [4.5-37.5%]) and overall survival (hazard ratio: 0.58 [0.35-0.96]) than nivolumab monotherapy. Conclusion:  Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had a superior efficacy versus cabozantinib 60 mg, regorafenib 160 mg and nivolumab 3 mg/kg monotherapy as second-line therapy for advanced hepatocellular carcinoma.

Introduction: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs)., Methods: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients' global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests., Results: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively., Conclusions: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission).

Background: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood., Objective: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class., Methods: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported., Results: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78-15.54]), one copy of APOE ɛ4 (1.94 [1.08-3.47]), higher baseline CDR-SB (2.46 [1.56-3.88]), lower baseline MMSE (0.85 [0.75-0.97]), and higher baseline FAQ (1.13 [1.02-1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar., Conclusion: Approximately a third of participants experienced progression based on CDR-SB or FAQ during the  4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

Objectives: Data on the economic burden associated with tuberous sclerosis complex (TSC) among patients with epilepsy in the United States (US) are limited. This study aimed to assess all-cause and epilepsy-related healthcare resource utilization (HRU) and healthcare costs in the US among patients with epilepsy and TSC compared with patients with epilepsy but without TSC., Methods: This retrospective study was conducted using the Symphony Health Solutions claims database (April 1, 2017-June 30, 2019). Patients with ≥1 medical claim with a diagnosis code representing epilepsy or seizures were assigned to the cohort with TSC if they had ≥1 medical claim for TSC; the remaining patients were assigned to the cohort without TSC. Patients in the cohort with TSC were exactly matched 1:5 on demographics to patients in the cohort without TSC. All-cause and epilepsy-related HRU, medical charges, prescription drug costs, and the use of antiepileptic drugs (AEDs) were compared between the matched cohorts over the 1-year study period., Results: A total of 2028 patients with epilepsy and TSC were matched to 10,140 patients with epilepsy but without TSC. Patients with TSC were more likely to have a diagnosis code for refractory epilepsy (38.7% vs. 10.2%, p < 0.001) and more likely to have used an AED (89.5% vs. 71.2%, p < 0.001) than patients without TSC over the study period. On average, patients with TSC received 2.1 distinct AEDs versus 1.3 distinct AEDs among patients without TSC. Compared with patients without TSC, patients with TSC had numerically but not statistically higher incidence rates of all-cause outpatient, clinic, office, and other visits; significantly lower rates of all-cause inpatient and emergency room visits (p < 0.001); and statistically significantly higher incidence rates of epilepsy-related outpatient, inpatient, office, and other visits (p ≤ 0.001). All-cause prescription drug costs were significantly higher among patients with TSC than patients without TSC (cost difference per patient: $14,179, p < 0.001). All-cause medical service charges were numerically higher for patients with TSC, but the differences were not statistically significant (charge difference per patient: $4293 for medical services, p = 0.707). Epilepsy-related costs were significantly higher for patients with TSC; the cost difference per patient was $14,639 for prescription costs (p < 0.001), and the charge difference per patient was $16,838 for medical charges (p = 0.019)., Conclusion: The results of this study underscore the high epilepsy-related HRU and costs incurred by patients with epilepsy and TSC relative to those incurred by patients with epilepsy but without TSC., Competing Interests: Declaration of competing interest Karen M. Stockl was an employee of Greenwich Biosciences, Inc. at the time this study was conducted and owns stock in the company. Kelly Hollenack is an employee of Greenwich Biosciences, Inc. and owns stock in the company. Keith A. Betts, Lei Yin, Min-Jung Wang, Xiaoran Yang are employees of Analysis Group Inc., which has received consultancy fees from Greenwich Biosciences, Inc., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)