Citations

Abstract Purpose We retrospectively compared 2 strategies for adalimumab biosimilar conversion at an academic medical center to better understand the effects of each strategy. Methods The formulary for our institution is managed by physician- and pharmacist-led task forces, in collaboration with our specialty pharmacy and pharmacy benefit manager. We implemented 2 phased strategies to increase adalimumab biosimilar utilization. First, we added preferred biosimilars to the formulary at parity to reference product and relied on prescribers to promote conversion. Second, we added an interchangeable biosimilar and removed reference product from the formulary while leveraging specialty pharmacy workflows for prescription conversions, streamlined facility inventory, and minimized dependence on prescriber workflows. For both strategies, we evaluated prescribing trends, dispensing data, and pharmaceutical spend for all medical center patients, specialty pharmacy patients, and patients with the top 3 specialty pharmacy payers. Results During phase 1 (quarter [Q] 2 of 2023 [2Q23] to 1Q24), reference product dispensing remained largely unchanged (<5% reduction). Phase 2 (2Q24 to 2Q25) resulted in a significant reduction in specialty pharmacy dispenses of reference product, from 95.7% to 19.0%. This phase also resulted in a 76.0% reduction in medical center adalimumab/biosimilar spend. At the end of phase 2, biosimilar accounted for 42.6% of all medical center patient prescriptions. Total dispensed units of reference product/biosimilar were modestly decreased (6%) during phase 2. Conclusion Formulary and clinical support for adalimumab biosimilar alone did not promote use over the reference product, but rapid and substantial biosimilar uptake was achieved after operational barriers were addressed.

ABSTRACT Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.

Background: Assessing craniocervical fibromuscular dysplasia (cc-FMD) can be challenging using cross-sectional imaging. We hypothesize that photon-counting detector CT (PCD-CT), owing to its superior spatial resolution over conventional energy-integrating detector CT (EID-CT), may better help appreciate changes in cc-FMD. Materials and Methods: In this retrospective cohort, 24 patients with radiologically reported cc-FMD (mean age: 54 y; 75% women) underwent both PCD-CT and EID-CT within 180 days (median: 52 d). Bilateral internal carotid (ICA) and vertebral artery (VA) segments without dissection/occlusion were graded on a 3-point scale (absent/likely present/present). Intermodality agreement was evaluated with weighted Cohen κ, and radiation dose metrics (CTDIvol) were compared using the paired Wilcoxon signed-rank tests. Results: Eighty-seven paired segments were analyzed. PCD-CT detected FMD in 48 segments (55.1%) versus 30 (34.5%) on EID-CT. The mean reader confidence scores were consistently higher with PCD-CT compared with EID-CT, for both ICAs (2.16±0.95 vs. 1.93±0.99) and VAs (1.86±0.95 vs. 1.36±0.75). Intermodality agreement was almost perfect for ICAs (κ=0.807) and substantial for VAs (κ=0.662). Under our institutional protocols, median CTDIvol was lower with PCD-CT (16.6 mGy) than EID-CT (21.5 mGy; P =0.0112). Conclusion: PCD-CT demonstrated more frequent reader categorization of cc-FMD features than EID-CT, particularly in the VAs, and had a lower median CTDIvol under our institutional protocols. These preliminary findings suggest improved cc-FMD detection with PCD-CT as compared with EID-CT and require prospective, reference-standard validation to establish accuracy and clinical impact.

BACKGROUND AND OBJECTIVES: Surgery for cervical spondylotic myelopathy improves quality of life but remains expensive. We conducted a cost-effectiveness analysis of patients treated with anterior cervical diskectomy/fusion (ACDF), posterior cervical decompression/fusion (PCDF), and laminoplasty (LP) in the Cervical Spondylotic Myelopathy Surgical (CSM-S) Trial, a randomized trial comparing surgical approaches for cervical spondylotic myelopathy. METHODS: In the trial, patients were randomized (2:3) to anterior (ACDF) or posterior surgery (LP or PCDF, at surgeon's discretion). A cost-effectiveness analysis was performed from a societal perspective with a 1-year time horizon, including only US patients as-treated. Cumulative costs were estimated using patient data on utilization and lost productivity using a human capital approach. Direct costs were calculated using 2022 Medicare rates for professional fees and cost-to-charge ratios for hospital services. Quality-adjusted life-years (QALYs) were calculated from patient responses to the EuroQol-5-Dimensions instrument at baseline and 3, 6, and 12 months postoperatively. Incremental cost-effectiveness ratio analysis was performed with bootstrapping to address uncertainty. RESULTS: Of 163 total patients enrolled in the CSM-S Trial, 153 from the United States (mean age, 62 years; 80 (52%) female) were included as-treated (ACDF = 61, PCDF = 64, LP = 28) in a cost-effectiveness analysis. Economic data were not available for 9 patients. The remaining 144 patients treated (ACDF = 55, PCDF = 61, LP = 28) had cost data through a 1-year follow-up. Mean hospitalization costs were higher after PCDF than ACDF and LP ($33 410 vs $26 468 vs $25 550; P < .001). Mean total costs were higher after PCDF than ACDF and LP ($62 383 vs $53 074 vs $47 426; P = .017). LP yielded greater QALY gains than ACDF (0.792 vs 0.732; P = .08) and PCDF (0.792 vs 0.698; P = .01). At a willingness-to-pay threshold of $150 000/QALY-gained, the probability that LP was cost-effective compared with PCDF was 99.7% and the probability compared with ACDF was 96%. CONCLUSION: In the CSM-S Trial, LP yielded greater 1-year quality-of-life improvements at lower costs than PCDF and ACDF.

Abstract: Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposition of insoluble proteins. Glucagon-like peptide-1 analog (AGLP1)-type amyloidosis is a rare iatrogenic form of amyloidosis localized to areas of glucagon-like peptide-1 analog injections. In this study, we describe a case of AGLP1-type amyloidosis presenting as a subcutaneous mass on the abdomen of a 71-year-old woman with a history of liraglutide, semaglutide, and tirzepatide use. Biopsy, including Congo red stain, was consistent with an amyloid deposit. Amyloid protein identification by liquid chromatography tandem mass spectrometry showed a typical amyloid profile with low spectra for liraglutide. Immunohistochemistry, subsequently performed, showed that the amyloid deposits were positive for glucagon; there is an extensive peptide homology between liraglutide and glucagon. Only 3 cases of AGLP1-type amyloidosis have been previously reported. It is vital for clinicians and pathologists to be aware of AGLP1-type amyloidosis given the increasing worldwide use of GLP-1 agonists, as well as the potential for misdiagnosis of systemic amyloidosis, which has profound therapeutic and prognostic implications.

Chimeric antigen receptor T-cell (CAR-T) and CD20xCD3 bispecific antibody (BsAb) therapies are both effective for relapsed/refractory (R/R) follicular lymphoma (FL), but comparative real-world survival outcomes and time toxicity have not been characterized. We performed a multicenter retrospective study of 228 patients with R/R FL treated with standard-of-care CAR-T (n = 141) or BsAb (n = 87) across 17 U.S. academic centers in the third-line or later setting. Progression-free survival (PFS) and overall survival (OS) were stratified by 2 or ≥3 prior lines of therapy (LOT2 or LOT3+), including propensity matching. Time toxicity was measured by physical health care contact days. Median PFS was not reached (NR) with CAR-T and 581 days with BsAb in the LOT2 cohort (p &lt; .0001), and was NR with CAR-T and 584 days with BsAb in the LOT3+ cohort (p = .0064). CAR-T recipients were younger (p &lt; .0001) and had better performance status (p = .007) but were more refractory to prior LOT (p = .017). PFS advantages of CAR-T were independent of these differences. OS did not differ between treatment groups. CAR-T had significantly greater time toxicity over the first year, with higher mean contact days than BsAb in both the LOT2 (58 vs 44) and LOT3+ (69 vs 49) cohorts. In this large multicenter cohort of patients with R/R FL, CAR-T was associated with superior PFS but greater time toxicity compared with BsAb therapy. These findings provide real-world outcomes data and time toxicity benchmarks to support treatment sequencing decision-making in R/R FL.

A thorough understanding of hand and wrist vascular anatomy and disease patterns, combined with strategic use of multimodality imaging, enables radiologists to diagnose vascular diseases, guide clinical management, and help preserve limb function.

Background Rhabdomyolysis is a complex and potentially life-threatening syndrome characterized by the rapid breakdown of damaged skeletal muscle. Despite its clinical significance, universally accepted diagnostic criteria and standardized management guidelines are lacking. Methods A cross-sectional online survey about the current diagnostic approach, assessment of risk factors and severity, and management of follow-up of rhabdomyolysis was conducted among clinicians across Europe, Australia, and the USA. Results Fifty-four respondents from 16 countries completed the survey. Results revealed considerable variability in hospital admission practices, and patient follow-up. Some agreement was found in the frequent use of genetic and neurophysiological testing in as diagnostic tools. The survey revealed no consensus on which CK-level would be considered cut-off levels for rhabdomyolysis. Conclusions The survey found little to no coherent approach to diagnosing, assessment of severity, nor follow-up of rhabdomyolysis among respondents who were primarily neurologists and pediatric neurologists. It highlights the need for international guidelines in the diagnostic process, treatment and follow-up of rhabdomyolysis as well as a universally agreed definition of rhabdomyolysis.