Advances in Therapy最新文献

Introduction

This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA).

Methods

Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May 2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6 months from treatment switch. Fatigue and treatment adherence were measured ≥ 6 months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA.

Results

Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111).

Conclusion

Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.

Introduction

Individuals living with Crohn’s disease (CD) experience burdensome symptoms. As such, it is important to measure CD symptom severity in clinical research. The goal of this study was to evaluate the content validity, psychometric performance, and score interpretability of a new patient-reported instrument, the Crohn’s Symptom Severity (CSS) questionnaire, among adolescents and adults with moderately to severely active CD.

Methods

Cognitive debriefing interviews (N = 30; n = 20 adults, n = 10 adolescents) were conducted to evaluate the content validity of the CSS. Additionally, the CSS scores were evaluated for reliability and validity using data from a phase 3 randomized clinical trial of risankizumab (NCT03105128; N = 850). Meaningful within-patient change (MWPC) thresholds were estimated using anchor-based methods.

Results

All interview participants (n = 30/30, 100.00%) reported the CSS was easy to complete and most participants (n = 28/29, 96.55%) reported that the CSS was relevant to their experience of CD. Among the clinical trial subjects (N = 850) the following was found for the CSS: mostly acceptable item–total correlations (0.26–0.79); weak to moderate inter-item correlations (r = 0.07–0.57), good internal consistency (Cronbach’s α = 0.76–0.87); intraclass correlation coefficients ranged from 0.48 to 0.70, not consistently exceeding the acceptable range for test–retest reliability (0.70); acceptable convergent validity and known-groups results; and demonstrated sensitivity to change. Analyses supported an MWPC estimate of 6–11 points.

Conclusions

This study supports use of the CSS for measuring CD symptoms and sleep impact among adolescents and adults aged 16 and older with moderately to severely active CD in clinical research.

Trial Registration

NCT03105128 (registration date 4 April 2017).

Introduction

Continuous glucose monitoring (CGM) devices allow for 24-h real-time measurement of interstitial glucose levels and have changed the interaction between people with diabetes and their health care providers. The large amount of data generated by CGM can be analyzed and evaluated using a set of standardized parameters, collectively named glucometrics. This review aims to provide a summary of the existing evidence on the use of glucometrics data and its impact on clinical practice based on published studies involving adults and children with type 1 diabetes (T1D) in Spain.

Methods

The PubMed and MEDES (Spanish Medical literature) databases were searched covering the years 2018–2022 and including clinical and observational studies, consensus guidelines, and meta-analyses on CGM and glucometrics conducted in Spain.

Results

A total of 16 observational studies were found on the use of CGM in Spain, which have shown that cases of severe hypoglycemia in children with T1D were greatly reduced after the introduction of CGM, resulting in a significant reduction in costs. Real-world data from Spain shows that CGM is associated with improved glycemic markers (increased time in range, reduced time below and above range, and glycemic variability), and that there is a relationship between glycemic variability and hypoglycemia. Also, CGM and analysis of glucometrics proved highly useful during the COVID-19 pandemic. New glucometrics, such as the glycemic risk index, or new mathematical approaches to the analysis of CGM-derived glucose data, such as “glucodensities,” could help patients to achieve better glycemic control in the future.

Conclusion

By using glucometrics in clinical practice, clinicians can better assess glycemic control and a patient's individual response to treatment.

Introduction

Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings.

Methods

Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method.

Results

As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60 years and prevalent (2 years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%–40% and 46–68 years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74–81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16–42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47–54%). Kaplan–Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively.

Conclusions

In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort.

A graphical abstract is available with this article.

Graphical Abstract

Introduction

Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner–Whitehouse 3 (TW-3) method.

Methods

Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts’ mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident.

Results

For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed.

Conclusion

In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.

Introduction

Insurance claims data and electronic health records (EHRs) have been used to characterize Duchenne muscular dystrophy (DMD) in real-world populations. The ability to assess patient-level DMD disease progression within insurance claims or EHR data infrastructures is unknown. Insurance claims and EHR data were comprehensively examined for availability and reliability of DMD outcomes that describe functional status and disease progression at the individual patient level over time.

Methods

MarketScan Commercial and Medicaid claims, and EHR-linked Clarivate open claims datasets were examined for data measuring 54 previously identified DMD-relevant outcomes in patients with DMD. Each outcome was assigned to one of five categories: functional and clinical events, clinical measures, biomarkers, functional measures, or patient-reported outcomes (PROs). Patients were identified using published coding algorithms. Annual 5-year attrition and data availability for each outcome was determined. The ability to distinguish disease severity and identify test results was also considered where applicable.

Results

A total of 1964 (MarketScan Commercial), 2007 (MarketScan Medicaid), and 10,639 (Clarivate) patients were identified. At 5 years, 31.7%, 35.1%, and 59.1% of patients remained in MarketScan Commercial, MarketScan Medicaid, and Clarivate, respectively. Claims were available for five of six functional and clinical events, with 45.5% (MarketScan Commercial), 48.0% (Clarivate), and 48.5% (MarketScan Medicaid) of patients with ≥ 1 claim for the most frequently identified clinical event (cardiomyopathy diagnosis). No data were available to describe frequency of wheelchair use or loss of ambulation. Very limited EHR data (≤ 2% of patients) were available to indicate tests were ordered for clinical measures, biomarkers, or functional assessments. No PRO notes or scores were observed. Data existed for inferring disease severity (e.g., hospitalization for cardiomyopathy); however, it was not apparent whether these events were incident.

Conclusion

Insurance claims and EHR-linked open claims data are of limited utility for holistically evaluating the progression and burden of DMD in individual patients.

Introduction

There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment.

Methods

Participants (≥ 65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60–89 mL/min for mild and 30–59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25 mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75 mg/h continuous intravenous (IV) infusion over 24 h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15 mg every 6 h. There were four treatment periods of 24 h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration–time profiles against target profiles. Adverse events were monitored.

Results

Thirty-nine subjects enrolled. Concentration–time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred.

Conclusions

NTM-001 was considered safe and well tolerated in this population of participants ≥ 65 years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.

Introduction

Understanding the patient journey of hepatocellular carcinoma (HCC) may inform future clinical decision-making and enhance the patient experience. The objectives of this study were to explore the patient experience of HCC in relation to treatment options, treatment decision-making and treatment goals throughout the disease journey. This study also aimed to determine the symptoms and impacts of HCC across early, intermediate and advanced HCC.

Methods

Semi-structured 60-min interviews were conducted with n = 50 patients with HCC and n = 12 healthcare professionals (HCPs) with experience of treating patients with HCC. Interview data were analyzed using directed content analysis techniques with a hybrid inductive and deductive approach. An assessment of conceptual saturation was conducted for patients' symptom experience.

Results

Patients described treatment decisions as mostly HCP-led. In this study, surgery/resection was the most frequently offered treatment option across the HCC journey, and most patients were satisfied with the treatment options presented to them. Overall, patients described extending their overall survival (OS) and preserving quality of life (QoL) as their most important treatment goals, with patients diagnosed with advanced/unresectable HCC prioritizing QoL. HCPs also prioritized OS and progression-free survival (PFS) though reported that QoL became more important as HCC progressed. Patients experienced various symptoms across the HCC journey including fatigue, nausea, appetite loss, diarrhea and pain.

Conclusion

Overall, HCPs and patients collaborate throughout the treatment journey regarding treatment decisions and shared treatment goals. OS is critically important to patients and HCPs, though treatment goals may change depending on various clinical factors.

Introduction

Symptom status and treatment changes among patients with chronic obstructive pulmonary disease (COPD) using inhaler treatment in real-world clinical settings are not well understood, particularly according to class of treatment. We investigated the proportion of symptomatic patients among those with COPD using inhaler treatment, based on COPD Assessment Test (CAT) scores in clinical practice, and changes in inhaler treatments and symptoms at 1-year follow-up.

Methods

This was a retrospective analysis of data from a multicenter, prospective cohort study conducted at medical institutions with respiratory specialists in Japan. The primary endpoint was the proportion of patients with CAT scores ≥ 10 or < 10 in each inhaler treatment group at registration.

Results

Of 414 patients in the full analysis set, 76 (18.4%), 261 (63.0%), and 77 (18.6%) were using long-acting muscarinic antagonist (LAMA), LAMA + long-acting β₂-agonist (LABA), and inhaled corticosteroids (ICS) + LABA, respectively, at registration. The proportions of patients with CAT scores ≥ 10 or < 10 per inhaler treatment group at registration, respectively, were 32.9% and 67.1% in the LAMA group, 55.0% and 45.0% in the LAMA + LABA group, and 50.0% and 50.0% in the ICS + LABA group. Most patients (> 75%) in each inhaler treatment group showed no change in inhaler treatment at 1 year, regardless of their CAT score at registration. Approximately 70–80% of patients with CAT scores ≥ 10 at registration still had CAT scores ≥ 10 at 1 year; 10–30% of patients with CAT scores < 10 at registration had CAT scores ≥ 10 at 1 year.

Conclusion

In real-world Japanese clinical practice, a considerable proportion of patients have persistent symptoms (CAT score ≥ 10) despite using mono or dual inhaler treatment; > 75% of symptomatic patients with COPD using inhaler treatment did not undergo treatment escalation at 1-year follow-up and remained symptomatic.

Trial Registration

ClinicalTrials.gov identifier, NCT05903989.