Advances in Therapy最新文献

Introduction: Three previous publications have reported real-world comparative effectiveness of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) in patients with chronic obstructive pulmonary disease (COPD) in the USA. This subgroup analysis assessed treatment with FF/UMEC/VI and BUG/GLY/FORM in patients with COPD who stepped up from dual therapy, stratified by number of prior exacerbations and class of prior dual therapy.

Methods: Propensity score (PS)-weighted patients identified within healthcare claims from the Komodo Research database were used to compare annualized rates and time to first moderate-severe COPD exacerbation between FF/UMEC/VI and BUD/GLY/FORM initiators stepping up from dual therapy, stratified by the type of dual therapy (long-acting muscarinic antagonist plus long-acting β₂-agonist [LAMA/LABA] or inhaled corticosteroid [ICS] plus LABA) and by prior (none or ≥ 1) COPD exacerbation. Results are presented as events per patient year (PPY) and rate ratio (RR) with 95% confidence intervals (CIs).

Results: Approximately 14,000 patients contributed to this analysis, 10,093 FF/UMEC/VI and 3926 BUD/GLY/FORM initiators. Baseline characteristics were well balanced following PS weighting. Step-up to FF/UMEC/VI was associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM irrespective of exacerbation history: no prior exacerbation, n = 7235, 0.48 vs 0.56 PPY, RR [95% CI] 0.86 [0.77, 0.95], P = 0.003; ≥ 1 prior exacerbation, n = 6784, 1.14 vs 1.41 PPY, RR [95% CI] 0.81 [0.74, 0.87], P < 0.001. Step-up to FF/UMEC/VI was also associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM across both subgroups of prior dual therapy: LAMA/LABA, n = 5717, 0.71 vs 0.95 PPY; RR [95% CI] 0.75 [0.67, 0.83], P < 0.001; ICS/LABA, n = 8302, 0.85 vs 0.99 PPY; RR [95% CI] 0.86 [0.79, 0.93], P < 0.001.

Conclusion: Patients newly initiating FF/UMEC/VI following prior treatment with ICS/LABA or LAMA/LABA experienced a significantly lower rate of moderate-severe COPD exacerbations than those newly initiating BUD/GLY/FORM irrespective of number of prior exacerbations or prior dual therapy class.

Introduction: The relative efficacy of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma (RRMM) was assessed via unanchored matching-adjusted indirect comparison (MAIC) using data from the CARTITUDE-4 and CARTITUDE-1 (cilta-cel) and KarMMa-3 (ide-cel) trials. This updated MAIC includes longer follow-up and overall survival (OS).

Methods: An unanchored MAIC was performed utilizing individual patient-level data (IPD) from CARTITUDE-4 [1-3 prior lines of therapy (LOT); n = 208] and CARTITUDE-1 (3-4 prior LOT; n = 37). Patients fulfilling KarMMa-3 inclusion criteria (2-4 prior LOT, triple-class exposed) were selected, and outcomes were compared against published aggregate KarMMa-3 data. Cilta-cel IPD were weighted to match reported baseline characteristics of KarMMa-3 on key prognostic factors identified a priori. Comparative efficacy was estimated for progression-free survival (PFS), OS, overall response rate, very good partial response (VGPR) or better rate, and complete response (CR) or better rate.

Results: Eighty-five patients from CARTITUDE-4 and CARTITUDE-1 were included. After adjustment, patients in the cilta-cel group (effective sample size = 39) had a 58% reduction in PFS risk [hazard ratio (HR) 0.42 (95% CI 0.26-0.68); p = 0.0004] and a 42% reduction in OS risk [HR 0.58 (0.34-0.99); p = 0.0452] versus ide-cel. Patients in the cilta-cel group were significantly more likely to achieve an overall response [relative response ratio (RR) 1.22 (95% CI 1.08-1.38); p = 0.0126] and deeper levels of response [≥ VGPR: RR 1.37 (1.19-1.59); p = 0.0009; ≥ CR: RR 1.80 (1.49-2.18); p < 0.0001] versus ide-cel.

Conclusion: This updated MAIC with longer follow-up time demonstrated significant superiority of cilta-cel over ide-cel in PFS, OS, and response outcomes in patients with triple-class exposed RRMM treated with 2-4 prior LOT. The OS results reinforce the added value of cilta-cel in this population.

Trial registration: ClinicalTrials.gov ID: CARTITUDE-1: NCT03548207; CARTITUDE-4: NCT04181827; KarMMa-3: NCT03651128.

Introduction: Psoriasis is a chronic inflammatory disease often accompanied by musculoskeletal symptoms and psoriatic arthritis (PsA). Early identification of PsA remains challenging, underscoring the need for interdisciplinary care between dermatology and rheumatology. To evaluate the diagnostic and therapeutic impact of an interdisciplinary dermatology-rheumatology board (IDRB) for patients with psoriasis, we initiated a non-randomized, prospective bicentric study.

Methods: A total of 182 patients with psoriasis were enrolled at baseline (V0), of whom 111 completed the 12-month follow-up (V2). Forty-seven (25.8%) patients participated in the IDRB, and 135 (74.2%) patients received standard dermatological care. Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS-A/D), pain, systemic inflammation, psoriatic arthritis (PsA) diagnosis, and systemic therapy courses were analyzed. Group differences and changes over time were assessed using non-parametric and parametric tests, and predictors of therapy modification were explored using univariate logistic regression.

Results: Over 12 months, patients in the IDRB group showed statistically significant improvements in PASI, DLQI, and HADS-A (all p ≤ 0.05). Among participants without PsA at baseline and with complete PsA documentation at follow-up, new PsA diagnoses occurred more often in the IDRB cohort (31%) than in standard care (9.8%) (Fisher's exact p = 0.0295; χ² p = 0.0360; OR = 4.14). In univariate analyses, higher baseline PASI, DLQI, and HADS-A values were each associated with subsequent therapy modification. Within the IDRB group, biologic treatments shifted over time toward IL-17- and IL-23-targeted agents, indicating a move toward more streamlined and targeted systemic therapy patterns compared with standard care.

Conclusion: An IDRB may contribute to more structured PsA assessment and to more informed therapeutic decisions in patients with psoriasis. Integrating objective clinical measures together with patient-reported burden appears crucial for guiding treatment modification and optimizing outcomes. Given the non-randomized, self-selected design, these findings should be interpreted as associations.

Trial registration: DRKS-Deutsches Register Klinischer Studien listing: DRKS00037907.

Introduction: Olutasidenib and ivosidenib are isocitrate dehydrogenase 1 (IDH1) inhibitors approved for relapsed/refractory (R/R) IDH1 mutant (IDH1m) acute myeloid leukemia (AML).

Methods: A matching-adjusted indirect comparison estimated relative treatment effects using registrational Phase I/II data for olutasidenib (Study 2102-HEM-101; individual patient data) and ivosidenib (Study AG120-C-001; study-level data) since a head-to-head trial is unlikely. Weights were estimated using a logistic propensity score model adjusted for pre-defined covariates identified from a literature review, validated by clinical experts. Eight covariates were determined to be the most important prognostic factors/effect modifiers for the target population as reported in the Food and Drug Administration labels: number of prior systemic therapies, age, prior hematopoietic stem cell transplantation, AML type, relapse type, cytogenetic risk, Eastern Cooperative Oncology Group performance status, and IDH1 mutation.

Results: Olutasidenib versus ivosidenib adjusted rates of complete remission (CR; odds ratio [OR] 1.12, 95% confidence interval [CI] 0.61-2.08), CR plus CR with partial hematologic recovery (CR + CRh; OR 0.83, 95% CI 0.46-1.50), and median CR duration (difference in medians 11.18 months, 95% CI - 4.30 to 22.72) were not significantly different. Median CR + CRh duration was significantly longer for olutasidenib (difference in medians 9.84 months, 95% CI 3.24-22.28), accompanied by a numerical non-significant trend in overall survival that should be considered exploratory (hazard ratio 0.75, 95% CI 0.53-1.07).

Conclusion: While not confirmatory, these findings may be clinically relevant in the context of this difficult-to-treat R/R IDH1m AML population.

Introduction: Hypochondroplasia (HCH) is a disproportionate short-statured skeletal dysplasia condition caused by gain-of-function pathogenic variants in the fibroblast growth receptor 3 gene (FGFR3). Although HCH typically becomes clinically apparent after the first year of life, when height discrepancy compared with the general population becomes more pronounced, diagnosis is often delayed by several years. Early recognition of HCH is challenging because of wide phenotypic variability and subtle clinical and radiographic features, leading to delayed or missed diagnosis. Furthermore, wide variant heterogeneity and restrictive testing criteria can contribute to diagnostic delays. Early diagnosis may facilitate timely clinical management and psychosocial support. However, no standardized diagnostic criteria for HCH currently exist, nor are diagnostic pathways well described in the literature.

Methods: In October 2024, 14 experts across multiple specialties completed an online survey on current clinical practices for diagnosing HCH. A subset convened in person to discuss strategies to optimize clinical diagnostic pathways, which were subsequently refined by the collective group.

Results: Age-specific diagnostic opportunities were identified. Prenatally, sonographic features of HCH may be detectable from approximately 20 weeks' gestation. Postnatally, features suggestive of HCH include a sustained fall in length/height centiles over the first 2 years of life, relative macrocephaly, neonatal seizures, and specific radiographic and neuroimaging findings. Between ages 2-3 years, a characteristic growth pattern including limb shortening and body disproportion may become evident. Neurocognitive involvement including neurodevelopmental challenges may become apparent. HCH should be considered in the differential diagnosis of idiopathic or isolated short stature. Genetic testing panels that include FGFR3 and evaluation of short-statured parents can support diagnosis.

Conclusion: Early diagnosis of HCH is achievable when age-specific key clinical and radiologic features are recognized and supported by molecular testing using appropriate diagnostic platforms. This work represents an important first step towards developing consensus-based diagnostic guidelines for HCH.

Introduction: Antimicrobial resistance (AMR) is exacerbated by the ongoing misuse of antibiotics for upper respiratory tract infections (URTIs), and it is vital to try and determine factors associated with antibiotic misuse. The Sore Throat and Antibiotic Resistance (STAR) study aims to evaluate public knowledge, perceptions, and behaviors to antibiotic use for acute URTIs and sore throat in Malaysia.

Methods: A nationwide online survey was carried out in June 2024 among Malaysian adults who reported having sore throats with other URTI symptoms in the past six months using a random sampling method. A 26-item (plus 5 for screening) self-administered questionnaire, adapted from the Eurobarometer survey on AMR, was shared through the Toluna online panel. The questionnaire included four sections that covered demographic details, URTI symptom patterns, antibiotic use, and self-medication practices for symptomatic relief, as well as knowledge, perceptions, and behaviors about these practices.

Results: Among 1031 respondents, sore throat was the most common symptom (62%). It often occurred significantly (p < 0.001) with cough (51.4%) and flu-like symptoms (53.8%). Antibiotic use was high, with 72% using them for respiratory illnesses and 33.4% for sore throat. Self-medication for symptomatic relief occurred mostly for sore throat (62%). While 78% had seen AMR messages and 70% knew about antibiotic risks, many held misconceptions: 66.1% thought antibiotics relieve pain and 72.5% believed they speed recovery. Confidence in non-antibiotic care was low at 42%, and 80% expressed anxiety about not using antibiotics. Unsafe behaviors included keeping leftover antibiotics (34%) and stopping treatment early (45%).

Conclusions: This study found a significant gap between perceived knowledge and practice as well as behaviors that contribute to inappropriate antibiotic use. These findings emphasize the need for targeted interventions such as public education, improved communication between healthcare providers and patients, including the benefits of a pro-symptomatic approach to first line management.

Introduction: Chronic kidney disease (CKD) is a leading cause of global morbidity and mortality, affecting one in ten Swiss adults. Patient numbers are expected to increase due to demographic shift and increasing comorbidity rates, necessitating strategic healthcare planning. Holistic burden remains unknown and detailed projections-including expectations of prospective economic and environmental impact-are lacking. To inform Switzerland's public health strategies and support its 2050 net-zero healthcare goal, this study aims to forecast the multidimensional burdens of CKD.

Methods: The IMPACT-CKD microsimulation model was utilised to project CKD-progression and clinical, healthcare resource utilisation, economic, societal, and environmental outcomes in Switzerland over 10 years (2023-2032). Modelled individuals were assigned CKD-relevant characteristics-including kidney function, comorbidities and clinical events-based on real-world data. Individuals were categorised into non-CKD or one of six CKD stages and progressed through the disease, diagnosed or undiagnosed. Model inputs and outcomes were validated and calibrated against literature, real-world evidence, and expert consultation.

Results: By 2032, IMPACT-CKD projects Switzerland's cases of CKD to rise by 6.7% (0.96m to 1.03m) with late-stage CKD and kidney replacement therapy (KRT) surging by 18.1% (437k to 516k) and 57.2% (8.4k to 13.2k). CKD-related healthcare costs are projected to increase by 27.6% (Swiss francs [CHF] 3.3b to CHF 4.2b), driven by a 77.3% rise KRT-related costs. CKD would account for 4.6% of the Swiss healthcare budget, incur CHF 12.9b in lost productivity, 43.2m missed workdays and CHF 606m in lost tax revenue. Greenhouse gas emissions are projected to increase by 12.9%, driven by rising dialysis demand.

Conclusion: IMPACT-CKD projects substantial increases in the multidimensional burdens of CKD in Switzerland. Impact could be mitigated via earlier detection and broader uptake of guideline-directed medical therapy. Comprehensive health policies and strategic public health planning are necessary to reduce burden and sustain Switzerland's 2050 net-zero healthcare ambition.

This Summary of Research summarizes a previously published original article, "Risdiplam treatment following onasemnogene abeparvovec in individuals with spinal muscular atrophy: a multicenter case series." Spinal muscular atrophy (SMA) is a rare genetic disease that causes muscle weakness and is associated with swallowing and breathing difficulties. Risdiplam (EVRYSDI^®) and onasemnogene abeparvovec (OA, ZOLGENSMA^®) are two medications approved by the US Food and Drug Administration for the treatment of individuals with SMA. This study explored the clinical benefits and safety of using risdiplam after OA in children with SMA. All children whose muscle movement was assessed showed stability or improvement after risdiplam initiation, and around one in three children saw improvements in swallowing and decreased usage of respiratory support. Risdiplam treatment was well tolerated. This study may help to improve understanding of the potential risks and benefits of using risdiplam treatment after OA treatment in children with SMA. Further studies including more children are necessary.

Introduction: Wilson disease (WD) is a rare inherited disorder that causes copper accumulation and can be fatal if untreated. This study used real-world data from the US Komodo Health claims database to describe healthcare resource utilization (HCRU) and evaluate direct economic costs among patients with WD.

Methods: This retrospective observational study identified patients with WD using ICD-9/10 codes (excluding Menkes disease) between 2016 and 2019, with data spanning 2012-2020. Sociodemographic characteristics, HCRU, and costs were analyzed using SPSS v23, SAS v9.4, and R v3.6.0. The study was approved by Pearl Pathways IRB (#20-KANT-224).

Results: A total of 2115 patients with prevalent WD, including 360 ever-treated (with reimbursable WD prescriptions), were identified. During the 2-year follow-up, about 25% were hospitalized, with a mean stay of 9 days, and most visited the ER three times annually. Hepatic patients with WD were more likely to undergo liver biopsy or transplant but had fewer home health visits and less use of assistive mobility devices. Annual liver transplant costs averaged $9094.72 ± 8110.23 per prevalent WD patient and $10,147.98 ± 7030.83 per ever-treated patient. Mean annual costs per prevalent versus ever-treated patients with WD were inpatient ($716.52 ± 2675.06 vs. $252.75 ± 333.39), pharmacy ($270.35 ± 1348.79 vs. $1284.51 ± 2994.85), and outpatient ($73.93 ± 156.89 vs. $60.82 ± 62.17), respectively. Pharmacy costs for adherent patients averaged $157,505.28 for any medication, $252,617.11 for D-penicillamine, $189,328.52 for trientine, and $1574.91 for zinc. Among ever-treated patients with WD, respective costs were lower at $85,117.60, $123,190.73, $100,017.20, and $820.35.

Conclusion: Estimated annual HCRU and treatment costs for patients with WD were lower than previously reported. These findings provide updated real-world insights into the economic burden of WD and highlight the cost implications of medication adherence in managing this rare disorder in the USA.

Introduction: Spinal muscular atrophy (SMA) is a rare, progressive, neuromuscular disorder that leads to loss of motor and respiratory function, affecting the individual's ability to work and life expectancy. The magnitude of productivity losses due to medical absenteeism and premature death associated with SMA is unknown. We estimated the productivity losses attributable to SMA in a working age population compared with the general working age population in Sweden.

Methods: This was a population-based, 1:4 matched cohort study of patients with SMA aged ≥ 18 years identified in the Swedish National Patient Registry from 2007 to 2019. Amongst those of working age (18-65 years), morbidity-induced productivity losses compared with a matched-reference cohort were estimated as the difference in the number of workdays lost attributable to SMA, monetised using mean income. Mortality-induced productivity losses were estimated as foregone lifetime earnings due to premature deaths for individuals with SMA compared with matched references, after adjusting for sex, age, and background unemployment.

Results: Overall, 172 adult patients with SMA were identified. Amongst those of working age, their average annual medical absenteeism was 100 days (95% confidence interval 61.5-138.1) higher than that of their references, leading to morbidity-induced productivity losses of €31,638 per patient per year alive whilst of productive age, of which €25,650 was directly attributable to SMA. Average mortality-induced productivity losses due to premature death were €108,253 for men and €87,160 for women with SMA.

Conclusions: Productivity losses due to medical absenteeism and premature mortality place a significant burden on adult patients with SMA of working age and Swedish society.