Advances in Therapy最新文献

Immune thrombocytopenia (ITP) is a rare autoimmune disease that results in low platelet counts and an increased risk of spontaneous bleeding due to impaired blood clotting. Several therapeutic approaches can be used to treat patients with ITP. However, many patients either lose response in the long term or are unable to maintain a response after treatment discontinuation, necessitating chronic treatment and multiple lines of therapy. Here, two patients with ITP share their experience, each providing a firsthand description of their ITP diagnosis, symptoms, management, and perspectives on the future. These stories are complemented by a clinical review of ITP pathophysiology, symptoms, and treatments presented by two expert hematologists who care for patients with ITP. The physician perspective reinforces the challenges faced by patients in everyday life and highlights the remaining areas of concern regarding the treatment of chronic ITP.

Introduction: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune neuromuscular disorder that currently lacks a curative treatment. Efgartigimod alfa is the first human IgG1 Fc fragment approved in Spain for the management of this condition. This study aims to evaluate the value of efgartigimod for treating gMG with anti-acetylcholine receptor (gMG AChR+) antibodies compared with ravulizumab, zilucoplan, and rozanolixizumab using a multi-criteria decision analysis (MCDA) framework.

Methods: A multidisciplinary group of eight experts evaluated the value of efgartigimod against ravulizumab, zilucoplan, and rozanolixizumab. The MCDA framework adapted for evaluating orphan drugs (ODs) in Spain, comprising nine quantitative and three qualitative criteria, was used.

Results: gMG AChR+ has been recognised as a severe and debilitating condition with considerable unmet needs. Efgartigimod achieved favourable average scores compared with ravulizumab, zilucoplan, and rozanolixizumab across all comparative parameters, including efficacy, safety, and patient-reported outcomes (PROs), potentially resulting in cost savings. Efgartigimod was deemed to have a significant therapeutic impact, with supporting data considered high quality. Efgartigimod alfa showed a higher overall value contribution than the three comparators, with the difference being most notable for ravulizumab. Furthermore, it was concluded that efgartigimod aligns well with the specific priorities, objectives, and capacities of the National Healthcare System (NHS).

Conclusion: Efgartigimod has been recognised as a valuable option for gMG AChR+ treatment in Spain by a multidisciplinary panel of experts through the application of MCDA, receiving higher scores compared with ravulizumab, zilucoplan, and rozanolixizumab.

Introduction: The long-term efficacy of biologics in psoriasis is compromised by primary or secondary resistance, and poor treatment adherence due to frequent dosing.

Methods: We assessed the efficacy and safety of switching to an interleukin-23 subunit p19 (IL23p19) inhibitor picankibart at 200 mg every 12 weeks, without a washout period, on skin clearance and quality of life (QoL) in patients with plaque psoriasis.

Results: A total of 152 patients were enrolled, comprising 83 suboptimal responders (static Physician's Global Assessment [sPGA] ≥ 2 or body surface area [BSA] ≥ 3%) and 69 clinical responders (sPGA0/1 and BSA < 3%). More than 96% had received IL-17A inhibitors. Among suboptimal responders, 48.2% achieved sPGA 0/1 and BSA < 3% at week 16 (W16), and the percentage increased to 54.2% at W44. Among responders, 82.6% maintained their therapeutic response at W44. The Dermatology Life Quality Index was reduced by 68.8% in suboptimal responders and by 61.5% in responders from baseline to W44. The most common adverse event was upper respiratory tract infection (25.0%).

Conclusion: Directly switching to picankibart resulted in clinically meaningful improvements in both skin lesions and QoL among suboptimal responders. Moreover, the majority of responders maintained their therapeutic response throughout the trial, accompanied by further enhancements in QoL. Picankibart was well tolerated without any new safety signals.

Trial registration: ClinicalTrials.gov identifier, NCT05970978.

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling and a deficiency of endogenous prostacyclin, a potent vasodilator with antiproliferative effects. Prostacyclin analogues (PCAs) target this deficiency and are integral to the PAH treatment algorithm. Parenteral PCA therapy is recommended for patients at intermediate-high and high risk, and early initiation-particularly in combination regimens-is associated with improved survival in real-world and post hoc analyses.The 2002 approval of the parenteral PCA treprostinil (Remodulin®) marked a significant advancement in PCA therapy. Compared with epoprostenol, treprostinil offers greater chemical stability at room temperature and a longer half-life, enabling subcutaneous (SC) infusion and minimizing the complications and challenges associated with intravenous delivery. Despite robust evidence demonstrating its benefits on morbidity and mortality and risk-based guideline recommendations, parenteral PCA therapy remains underutilized. Contributing factors include concerns about the complexity and perceived burden of pump-based delivery systems.Here we review the place for parenteral prostacyclin in PAH therapy, and the evolution of SC PCA pumps over time, with a focus on recent enhancements intended to overcome practical limitations of older devices and thereby improve usability. Key features such as simplified cassette filling, automated priming, a larger and more intuitive touchscreen remote, and expanded flow rate options aim to reduce the perceived challenges of SC therapy and support broader adoption among patients and prescribers. The article also provides perspectives and practical guidance from experienced practitioners on the initiation and maintenance of SC PCA therapy, emphasizing how improvements in pump technology can help overcome barriers to use. Addressing these challenges through improved design, education, and support may help bridge the gap between evidence-based recommendations and real-world practice.Graphical abstract available for this article.

Introduction: Atopic dermatitis (AD), a chronic type 2 inflammatory disease, often requires long-term therapeutic intervention. Understanding the long-term safety profile of dupilumab treatment is crucial for clinicians and patients, especially regarding laboratory parameters.

Methods: LIBERTY AD OLE, a phase 3, multicenter, open-label extension (OLE) study, evaluated clinical laboratory findings in adults with moderate-to-severe AD treated with dupilumab for up to 5 years.

Results: In total, 2677 patients entered the OLE study. At the time of database lock, 238 patients completed up to week 272 and 1297 patients completed treatment or the end-of-study visit. There were no clinically meaningful changes from baseline values in mean hematology or serum chemistry parameters. Few laboratory abnormalities were reported as treatment-emergent adverse events (TEAEs), most of which were not serious and did not lead to permanent drug discontinuation. Five serious laboratory-related TEAEs occurred in one patient each (number of patients [nP]/100 patient-years [PY], 0.02): febrile neutropenia, hemolytic anemia, thrombocytopenia, hypokalemia, and hematuria. Six laboratory-related TEAEs led to permanent treatment discontinuation: one case each (nP/100 PY, 0.02) of increased alanine aminotransferase, increased aspartate aminotransferase, increased blood creatine phosphokinase, and increased transaminases and two cases of thrombocytopenia (nP/100 PY, 0.03); although rare, some were related to the study drug. Serious laboratory-related TEAEs and TEAEs leading to study discontinuation were generally lower in our study than in the placebo arm of the 1-year LIBERTY AD CHRONOS study, which was included for comparison. Most of these TEAEs were considered unrelated to the study drug and were recovered/resolved during the study period. No deaths due to laboratory-related TEAEs were reported.

Conclusions: Treatment with dupilumab for up to 5 years showed no clinically meaningful changes in mean laboratory parameters. Continuous long-term use of dupilumab in adults with moderate-to-severe AD does not require laboratory testing before initiating or during the treatment.

Trial registration: ClinicalTrials.gov identifiers NCT01949311 and NCT02260986.

Introduction: There is an increasing demand for information on the environmental impact of medical devices from decision-makers in healthcare. Performing 'comprehensive' life cycle assessments (LCA) can be time and resource intensive to undertake. We present a screening LCA approach (scLCA) to streamline the LCA process for device manufacturers, intended to provide comparable results to more comprehensive assessments.

Methods: The scLCA is similar to the 'comprehensive' LCA in scope (cradle to grave) and methodology. In the scLCA two key changes are made to the LCA methodology: the use of standardized models for transport and product end-of-life. Furthermore, result interpretation is via a hotspot analysis and the validation process does not include an external review. The application of scLCAs is presented here with examples from three dialysis machines, where the functional unit is the production and operation of one dialysis machine over its lifetime.

Results: All three dialysis machines showed similar hotspots, with the main drivers of environmental impact being water and electricity consumption during use. Using the scLCA is an efficient approach to perform environmental assessments on multiple products. The results of the scLCA provide an informative hotspot analysis that can be used to target improved sustainability of the device's manufacturing and distribution process.

Conclusion: The scLCA makes performing environmental assessments more feasible for manufacturers while generating results comparable to 'comprehensive' LCAs.

Introduction: Combining ezetimibe (EZ) and statins is recommended for the treatment of elevated low-density lipoprotein-cholesterol (LDL-C). This subgroup analysis evaluated the efficacy of fixed-dose combination (FDC) therapy with EZ and atorvastatin (AS) versus AS monotherapy on attaining LDL-C goals in Chinese patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) grouped by ASCVD risk, age, and sex.

Methods: Data from the phase III, randomized, double-blind study (NCT03768427) compared EZ10/AS10 mg FDC versus AS20 mg (cohort A), and EZ10/AS20 mg FDC versus AS40 mg monotherapy (cohort B) in Chinese patients with uncontrolled hypercholesterolemia. Proportions of patients attaining 2016 Chinese guideline-recommended LDL-C goals (low/medium risk [< 130 mg/dL], high risk [< 100 mg/dL], very high risk [< 70 mg/dL]) were assessed at weeks 6 and 12. Subgroup analyses by ASCVD risk, age (< 65 and ≥ 65 years), and sex were conducted.

Results: LDL-C goal attainment was significantly higher with FDCs versus AS monotherapy at week 12 (cohort A: 62.7% vs. 35.1%, P = 0.0009; cohort B: 67.5% vs. 31.0%, P < 0.0001). A greater proportion of patients with very high ASCVD risk attained LDL-C goals with FDCs versus AS monotherapy at week 12 (cohort A: 62.3% vs. 33.9%; cohort B: 69.1% vs. 29.5%). LDL-C goal attainment was higher with FDCs versus individual doses of AS at weeks 6 and 12 in both cohorts, regardless of age or sex.

Conclusion: FDCs significantly improved LDL-C goal attainment compared to AS monotherapy in patients with very high ASCVD risk. In the subgroups by age and sex, a higher proportion of patients with uncontrolled hypercholesterolemia attained their LDL-C goals.

Trial registry: Trial registration number NCT03768427.