Advances in Therapy最新文献

Introduction

The global Communicating Needs and Features of Inflammatory Bowel Disease Experiences (CONFIDE) study aimed to evaluate the impact of ulcerative colitis (UC)- and Crohn’s disease (CD)-related symptoms on patients’ lives and elucidate communication gaps between patients and health care professionals (HCPs). We report the findings from the study in patients with UC or CD and HCPs in Japan.

Methods

Online, quantitative, cross-sectional surveys were conducted in Japan for patients with moderate-to-severe UC or CD and HCPs responsible for the care of patients with UC and/or CD. Subgroup analyses based on disease activity were conducted using the Manitoba Inflammatory Bowel Disease Index. Data were described using descriptive statistics.

Results

Surveys were completed by 124 patients with UC, 99 patients with CD, and 100 HCPs in Japan. Differences were noted in the most common patient-reported symptoms experienced in the month prior to survey completion between patients with UC and CD (diarrhea [45.2% UC, 68.7% CD], flatulence [34.7% UC, 32.3% CD], increased stool frequency [32.3% UC, 43.4% CD], bowel urgency [BU; 25.0% UC, 32.3% CD], and fatigue [36.4% CD]). More patients with active disease than inactive disease reported these symptoms. BU and BU-related accidents were among the symptoms ranked as most impactful by patients with UC and CD. HCP-perceived symptoms with the greatest impact on patients were diarrhea and blood in stool. Findings in the Japanese cohort of CONFIDE were generally consistent with those in the United States (US)/European cohorts. The percentage of patients reporting BU as the symptom with the greatest impact was higher in the US/European cohorts than in the Japanese cohort, potentially as a result of differences in baseline characteristics and social environments such as toilet facilities.

Conclusion

BU is an impactful symptom among Japanese patients with UC and CD and should be considered by HCPs during treatment of these conditions.

Physical inactivity (PIA) is a pressing public health issue globally, contributing significantly to the rise of non-communicable diseases (NCD), such as cardiovascular disease and type 2 diabetes. The World Health Organization emphasises the importance of regular physical activity (PA) for preventing and managing NCDs. Initiatives to promote active living have gained momentum, ranging from community programs to workplace wellness campaigns, all focused on reducing sedentary lifestyles in modern society. Structured Physical Activity—Dance, Exercise, and Sports (SPADES) has emerged as an innovative approach to addressing PIA and promoting holistic health. After thoroughly reviewing existing literature from PubMed and Google Scholar databases, a panel of experts developed consensus statements through in-depth discussions, and the strength of concurrence on these statements was voted on using a Likert scale. The panel reached a consensus on the best strategies for PA, dance, exercise, sports, and key factors to consider during PA. This consensus targets individuals with metabolic diseases, particularly in regions like South Asia, East Africa, the Gulf, and Latin America, where these conditions are highly prevalent. The SPADES guidelines emphasise overcoming the barriers people with metabolic disorders face in achieving adequate PA, providing tailored recommendations to improve health outcomes for this population.

Introduction

This study aimed to establish and apply a multicriteria value framework to determine the value of prophylaxis versus on‑demand treatment in adult patients with hemophilia A in China, which could enhance evidence-based care decisions.

Methods

The framework was developed using key literature to identify dimensions and indicators for assessing the value of hemophilia A. We interviewed 21 stakeholders—including clinical experts, medical insurance experts, health economics and outcomes research (HEOR) experts, charity organization representatives, and patient advocacy organization representatives—to evaluate the relative importance of indicators. The interviewees also assessed the value of prophylaxis and on-demand treatments for adults, providing justification for their ratings. The analytic hierarchy process (AHP) was employed to calculate the weight of each indicator based on stakeholder ratings. A linear additive value function was used to calculate total value scores. The main outcomes of the study include the weighted indicators of the value framework and the comprehensive value scores for different hemophilia A care strategies.

Results

The primary indicators in the value framework were clinical value, economic value, patient value, and social value. These were further broken down into nine secondary indicators. Overall, interviewees rated patient value highest (32.88%), followed by clinical value (30.08%), social value (22.25%), and economic value (14.79%). The adult prophylaxis strategy scored higher than on-demand treatment in all four primary value categories, with the largest difference observed in patient value. The total value score for adult prophylaxis (8.42) was higher than that for on-demand treatment (5.90), with an absolute difference of 2.52 (95% confidence interval [CI] 1.68–3.36).

Conclusion

The hemophilia value framework affirmed value of prophylaxis for adult patients with hemophilia A versus on-demand treatment, with benefit in terms of clinical value, economic value, patient value, and social value. The study also demonstrates that the value framework is an excellent tool for assisting stakeholders in decision-making that is grounded in patient-centered value in China.

Introduction

Pemphigus diseases are a family of chronic, autoimmune, blistering skin conditions. Despite advances in treatment approaches, more effective and safer therapies for pemphigus are urgently needed. Trials investigating novel therapeutics must be designed to yield evidence that can be compared to existing data, necessitating a comprehensive understanding of the clinical trial landscape. We aimed to perform a mapping review to assess the comparability of randomized controlled trials (RCTs) evaluating existing treatments for pemphigus vulgaris (PV) and pemphigus foliaceous (PF).

Methods

Embase, MEDLINE, and Cochrane Library were systematically searched from inception to July 2023, supplemented with conference abstracts, clinical trial registries, and grey literature searches, for RCTs evaluating pharmacotherapies in adults with moderate-to-severe PV or PF. Comparability of study populations (demographic and clinical characteristics), interventions and comparators (dose, administration route, regimen), and outcomes (definition, time point, measure) across trials was assessed.

Results

Fifteen RCTs were eligible for inclusion. Substantial heterogeneity was observed in participant age, sex, and disease duration at baseline, and none of the studies used the same criteria to assess illness severity. Doses and regimens differed across trials assessing the same interventions. Across 16 outcome measures extracted, clinical remission outcomes had limited comparability across studies and were often not defined according to published guidelines. Cumulative corticosteroid dose during the study period had the highest comparability. Health-related quality of life data and serious adverse events were infrequently reported.

Conclusions

The lack of comparability across studies has major implications for developers of new treatments for PV and PF and for decision-makers who must evaluate the efficacy, safety, and cost-effectiveness of these treatments relative to existing therapeutics.

Introduction

Use of niraparib and abiraterone acetate (AA; abiraterone prodrug) in patients with metastatic castration-resistant prostate cancer (mCRPC) targets two oncogenic drivers: homologous recombination repair (HRR) gene alterations and the androgen-receptor axis. Fixed-dose niraparib/AA combination is available as regular-strength dual-action tablets (RS-DAT; 200 mg/1000 mg) and low-strength DAT (LS-DAT; 100 mg/1000 mg, enabling niraparib dose reduction). We characterized the population pharmacokinetics (PPK) of niraparib and abiraterone, administered alone or in combination, in patients with mCRPC.

Methods

PPK modeling and covariate analysis using a non-linear mixed-effect modeling approach were conducted using pooled PK data from patients with mCRPC enrolled in the BEDIVERE (NCT02924766), GALAHAD (NCT02854436), QUEST (NCT03431350), and MAGNITUDE (NCT03748641) studies and in a study of relative bioavailability for LS-DAT and bioequivalence for RS-DAT. In all but GALAHAD (niraparib monotherapy), AA + prednisone was given alone or with niraparib. Overall, 9935 and 6289 niraparib and abiraterone plasma PK samples from 916 and 954 patients, respectively, were available.

Results

Niraparib and abiraterone PK were adequately described by an open two-compartment disposition model with linear elimination, with a zero-order rate of drug release into the depot compartment followed by first-order absorption (via two transit compartments for abiraterone) into the central compartment. For niraparib, identified covariates were creatinine clearance on apparent oral clearance; LS-DAT on zero-order drug-release duration and apparent oral bioavailability; HRR status on apparent oral clearance; race on first-order absorption-rate constant, intercompartmental clearance, and peripheral compartment volume of distribution. Covariate effects had no clinically relevant impact on niraparib exposure, warranting no dose adjustments. For abiraterone, RS-DAT was the only newly identified covariate on apparent oral bioavailability, first-order absorption-rate constant, and zero-order drug-release duration; however, effect magnitude was deemed not clinically relevant.

Conclusion

PPK analyses support the selected clinical dosage of RS-DAT (200-mg niraparib/1000-mg AA) plus 10-mg prednisone daily for treating patients with mCRPC and HRR gene alterations.

Graphical Abstract

Introduction

This study assessed the effects of astaxanthin supplementation on chronic and acute digital eye strain in school-aged children (10–14 years) and evaluated its safety. While previous studies focused on adults, this study examined astaxanthin’s effects on developing eyes.

Methods

A randomized, double-blind, placebo-controlled trial was conducted over 84 days involving 64 children engaged in ≥ 4 h of screen time daily and experiencing mild to moderate computer vision syndrome (CVS) symptoms as indicated by a CVS-Questionnaire (CVS-Q) score ≥ 8 and < 19. Participants received a daily 4-mg astaxanthin soft capsule for 84 days. Primary outcomes were measured using CVS-Q, while secondary outcomes included visual fatigue Likert scale (VFLS), visual acuity, spherical equivalence, near point of accommodation, near exophoria, dry eye intensity, pupil size, stereopsis, blinking frequency, immunity, and safety variables.

Results

Of the 64 participants (mean age 11.5–11.7 years), 35 were male and 29 were female. Astaxanthin supplementation significantly improved CVS-Q scores after 84 days (− 4.00 ± 4.05 arbitrary units (A.U.) from baseline, p < 0.0001) compared to placebo (− 1.72 ± 3.61 A.U., p < 0.05), a 20% between group difference. The mean VFLS scores were significantly lower in the astaxanthin group (11.55 ± 5.78 A.U.) compared to placebo (15.78 ± 7.12 A.U., p = 0.01), showing a 27% improvement after 84 days. Stereopsis improved significantly after acute visual load at 28 and 84 days (p < 0.05, p < 0.0001 vs. placebo, respectively), and pupillary light reflex improved after 84 days (p < 0.05 vs. placebo). Tear production increased after 14, 56, and 84 days (p < 0.05, p < 0.001, and p < 0.001 vs. baseline, respectively) in the astaxanthin group, with no significant intergroup difference in the Schirmer I test, visual acuity, spherical equivalence, near point of accommodation, near exphoria, immune markers, or safety variables.

Conclusion

Astaxanthin supplementation effectively reduced chronic and acute digital eye strain, while enhancing objective measures of visual performance in school-aged children, underscoring the benefits of astaxanthin in pediatric visual health and performance.

Trial Registration

NIH ClinicalTrials.gov (Identifier: NCT05602402); Clinical Trials Registry India (Registration Number: CTRI/2022/10/046606).

Introduction

The treat-to-target concept established goals to guide treatment with systemic therapies in atopic dermatitis (AD), including goals for itch improvement, reported as the most burdensome symptom. The aim of this study is to assess optimal itch response onset and long-term maintenance using treat-to-target criteria in dupilumab-treated patients.

Methods

This post hoc analysis assessed patients ≥ 18 years with moderate-to-severe AD in two phase 3, randomized, double-blind, placebo-controlled studies. Patients received dupilumab 300 mg every 2 weeks or placebo with concomitant topical corticosteroids (TCS) for 52 weeks (CHRONOS); or dupilumab monotherapy 300 mg every week/every 2 weeks/every 4 weeks/every 8 weeks or placebo for 36 weeks after achieving Eczema Area and Severity Index improvement of 75% or Investigator’s Global Assessment 0/1 with dupilumab in SOLO1/2 (SOLO-CONTINUE). Optimal itch response was defined as Peak Pruritus Numeric Rating Scale ≤ 4.

Results

Patients receiving dupilumab + TCS achieved optimal itch response faster and in higher proportion than those receiving placebo + TCS (P < 0.0001) and maintained optimal response longer (median [Q1–Q3] 40 [11–50] vs 3 [0–23] weeks; P < 0.0001). Patients achieving optimal itch response with dupilumab monotherapy who continued treatment maintained response longer compared with those transitioned to placebo, although duration decreased with less frequent dosing (P < 0.0001 for all dupilumab regimens vs placebo).

Conclusion

Optimal itch response was achieved rapidly and maintained long term in adult patients treated with dupilumab with or without concomitant TCS therapy.

Trial Registration

NCT02395133 and NCT02260986.

Introduction

Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.

Methods

LymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry. Times to ALC reconstitution and lymphopenia were estimated by the Kaplan–Meier method. Univariate and multivariate analyses evaluated factors associated with ALC reconstitution after DMF discontinuation or lymphopenia after DMF initiation. Patients treated with DMF for ≥ 3 months with ≥ 1 ALC in the 6 months before/close to DMF initiation and ≥ 1 ALC during treatment were included.

Results

Overall, 1429 RRMS patients were included; 356 patients developed lymphopenia, of whom 183 discontinued DMF. Overall, ALC decreased by 33% over the first year and plateaued thereafter. The probability of developing lymphopenia was 18.2% after 1 year. In patients with lymphopenia, median times to ALC reconstitution after DMF discontinuation were 3.8 months overall, 4.0 months for Grade 1 lymphopenia, 3.0 months for Grade 2, and 9.7 months for Grade 3. At 12 months, 83.0% had reconstituted ALC. In DMF discontinuers, median time to discontinuation was 1.2 years. There was no increased risk of serious or opportunistic infections in patients with lymphopenia. No cases of progressive multifocal leukoencephalopathy were reported. First ALC reconstitution after DMF discontinuation was associated with diabetes, DMF duration, DMF duration before lymphopenia, and DMF duration after lymphopenia; first lymphopenia after DMF initiation was associated with age and ALC at DMF initiation.

Conclusion

LymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit–risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution.

Trial Registration

ClinicalTrials.gov NCT04756687.

Introduction

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is often associated with persistent symptoms and impaired quality of life despite treatment with intranasal corticosteroids. Biologics (dupilumab, mepolizumab, omalizumab) have been recently approved for CRSwNP. This study aims to characterize biologic use and real-world outcomes, including medication use and nasal polyps (NP) surgeries, following biologic treatment in US patients with CRSwNP.

Methods

This retrospective cohort study analyzed linked data from IQVIA longitudinal prescription and medical claims databases (July 2018–June 2023). Patients evaluated included those with ≥ 2 diagnoses of CRSwNP and ≥ 12 months of baseline data (overall cohort, index = first observed CRSwNP diagnosis) as well as patients with CRSwNP who received ≥ 2 consecutive biologic doses and had ≥ 24 months of follow-up data (biologic cohort, index = first biologic).

Results

Of 74,480 patients with CRSwNP, 8716 (12.0%) received a biologic and 2208 met all inclusion criteria. Dupilumab was the most frequently received biologic (89.8%; mepolizumab, 5.3%; omalizumab, 4.8%). Relative to the overall cohort, the biologic cohort was younger (mean age: 52.6 vs. 57.6 years), had more women (54.0% vs. 46.1%) and had a higher baseline prevalence of asthma (72.4% vs. 30.9%), allergic rhinitis (70.6% vs. 37.4%), NP surgery (15.8% vs. 5.8%), oral corticosteroid (OCS) use (84.0% vs. 51.8%), and antibiotic use (84.2% vs. 68.7%). During the 24 months after biologic initiation, 65.6% of patients had ≥ 1 OCS use (≥ 2 OCS uses during months 1–12, 27.0%; during months 13–24, 27.0%) and 77.9% had ≥ 1 antibiotic use; and 7.1% of patients without NP surgery before biologic initiation had ≥ 1 NP surgery during follow-up. Almost half of patients (49.3%) discontinued (≥ 90 days without receipt) their initial biologic during follow-up.

Conclusion

Biologic use was relatively low among US patients with CRSwNP. OCS and antibiotic usage among patients with CRSwNP remained substantial despite use of currently approved biologics, indicating an unmet need for improved treatment options.

Pulmonary hypertension (PH) is a progressive syndrome characterized by increased pulmonary artery pressure. PH often complicates chronic lung diseases, thus contributing to a substantial disease burden and poor prognosis. The WHO Group 3 Pulmonary Hypertension has many subcategories, including sleep-hypoventilation PH, high altitude-PH, chronic obstructive pulmonary disease (COPD)-PH, and interstitial lung disease (PH-ILD), the latter carrying the worst prognosis. ILD is a heterogeneous group of disorders characterized by cough and shortness of breath and, in progressive forms, irreversible loss of function and respiratory failure. The development of PH in patients with ILD worsens exercise capacity and exertional dyspnea and impairs quality of life. Thus, suspicion and early detection of PH following thorough cardiologic evaluation (i.e., echocardiography, pro-BNP, and right heart catheterization) is paramount for appropriate patient management. For PH secondary to chronic respiratory diseases, current guidelines recommend optimizing the treatment of the underlying respiratory condition and offering long-term oxygen therapy. In recent years, several clinical trials have failed to identify drugs beneficial for group 3 PH. Conversely, the INCREASE trial of inhaled treprostinil has recently provided hope for treating PH-ILD. In this review, we summarize and critically discuss the present and future of the pharmacological management of PH-ILD.