Corrigendum to 'Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis' [Research and Practice in Thrombosis and Haemostasis, Volume 7, Issue 2, February 2023, 100077].

[This corrects the article DOI: 10.1016/j.rpth.2023.100077.].

Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis.

Background: Across the HAVEN clinical trial program, the efficacy of emicizumab has been demonstrated in children, adolescents, and adults with hemophilia A, with or without factor VIII inhibitors. After the 4-week loading dose period, emicizumab concentrations are expected to remain at levels that provide bleed protection throughout the entire dosing interval, regardless of the chosen maintenance dosing regimen, ie, weekly, every 2 weeks, or every 4 weeks. Objectives: The objective of this study was to examine the timing of treated bleeds within the dosing intervals for emicizumab administered during the HAVEN 1 to 4 studies. Methods: In this post hoc analysis, we pooled data from all the participants of the HAVEN 1 to 4 studies and analyzed the timing of treated bleeds in relation to the emicizumab dose. Results: A total of 392 participants were included in this analysis, with a median (range) age of 28.0 years (1.1-77.0 years). Target joints were identified in 237 of 392 (60.5%) participants before the study entry. Overall, 211 of 392 (53.8%) participants experienced 907 treated bleeding events. The total mean (SD) annualized bleeding rate across the 4 studies was 1.6 (5.9). There was no evidence that bleeding events clustered on any 1 particular day in any dosing schedule from HAVEN 1 to 4 (P > .05 for all 3 treatment regimens). Conclusion: Data from the HAVEN 1 to 4 trials show consistent bleed prevention within the dosing interval, regardless of the dosing regimen chosen. These findings provide further evidence of the sustained efficacy of emicizumab across all approved dosing regimens to reduce bleeding in people with hemophilia A.

Real-World Clinical Outcomes Based on Body Mass Index and Annualized Weight Change in Patients with Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Identification of clinical characteristics associated with prognosis for idiopathic pulmonary fibrosis (IPF) may help to guide management decisions. This analysis utilized data from the Pulmonary Fibrosis Foundation Patient Registry to examine the relationships between clinical outcomes and both body mass index (BMI) at study enrollment (hereafter referred to as baseline BMI) and annualized percent change in body weight in patients with IPF in a real-world setting. METHODS: The following outcomes over 24 months were stratified by baseline BMI and annualized percent change in body weight: all-cause mortality; annualized change in percent predicted forced vital capacity (%FVC), percent predicted diffusing capacity for carbon monoxide, and 6-min walk distance; all-cause and respiratory-related hospitalizations; and acute exacerbations. RESULTS: Overall, 600 patients with IPF were included (baseline BMI: < 25 kg/m2, n = 120; 25 to < 30 kg/m2, n = 242; ≥ 30 kg/m2, n = 238; annualized percent change in body weight: no loss, n = 95; > 0% to < 5% loss, n = 425; ≥ 5% loss, n = 80). Enrollment demographics and characteristics were generally similar across subgroups. There was no association between mortality and BMI. All-cause mortality was lower among patients who experienced no annualized weight loss versus those with ≥ 5% (OR [95% CI] 3.28 [1.15, 10.95]) or > 0 to < 5% weight loss (OR [95% CI] 2.83 [1.14, 8.62]) over 24 months. Patients with baseline BMI < 25 kg/m2 had a significantly greater estimated annualized decline in %FVC versus patients with baseline BMI ≥ 30 kg/m2 (difference [95% CI] 1.47 [0.01, 2.93]). No relationship was observed between %FVC and weight loss. Other clinical outcomes were generally similar across subgroups. CONCLUSIONS: Some clinical outcomes may be worse in patients with IPF who have a low BMI (< 25 kg/m2) or who experience weight loss over 24 months, but the causation for these relationships is unknown. These results may help to inform management decisions for patients with IPF. GOV IDENTIFIER: NCT02758808.

A Patient-Centered Evaluation of Meaningful Change on the 32-Item Motor Function Measure in Spinal Muscular Atrophy Using Qualitative and Quantitative Data.

The 32-item Motor Function Measure (MFM32) is an assessment of motor function used to evaluate fine and gross motor ability in patients with neuromuscular disorders, including spinal muscular atrophy (SMA). Reliability and validity of the MFM32 have been documented in individuals with SMA. Through semi-structured qualitative interviews (N = 40) and an online survey in eight countries (N = 217) with individuals with Types 2 and 3 SMA aged 2-59 years old and caregivers, the meaning of changes on a patient-friendly version of the MFM32 was explored. In an independent analysis of clinical trial data, anchor- and distribution-based analyses were conducted in a sample of individuals with Type 2 and non-ambulant Type 3 SMA to estimate patient-centered quantitative MFM32 meaningful change thresholds. The results from this study demonstrate that, based on patient and caregiver insights, maintaining functional ability as assessed by a patient-friendly version of the MFM32 is an important outcome. Quantitative analyses using multiple anchors (median age range of 5-8 years old across anchor groups) indicated that an ~3-point improvement in MFM32 total score represents meaningful change at the individual patient level. Overall, the qualitative and quantitative findings from this study support the importance of examining a range of meaningful change thresholds on the MFM32 including ≥0 points change reflecting stabilization or improvement and ≥3 points change reflecting a higher threshold of improvement. Future research is needed to explore quantitative differences in meaningful change on the MFM32 based on age and functional subgroups.

Randomized trial of efficacy and safety of dornase alfa delivered by eRapid nebulizer in cystic fibrosis patients.

BACKGROUND: Dornase alfa administered via jet nebulizer is indicated as a chronic respiratory medication for cystic fibrosis (CF) patients. Efficacy and safety of dornase alfa via an electronic nebulizer with vibrating membrane technology have not been formally assessed in randomized clinical trials. METHODS: 87 CF patients (≥6 years) were randomized in a crossover study to receive dornase alfa 2.5 mg/d in 2-week periods with the Pari eRapid and Pari LC Plus jet nebulizers. The primary end point was comparison of forced expiratory volume in the first second. Safety, quality of life, and treatment satisfaction/preference were also compared between devices. RESULTS: Lung function was equivalent between nebulizers. Most domain scores from the Cystic Fibrosis Questionnaire-Revised and Treatment Satisfaction Questionnaire for Medication instruments were similar but patients strongly preferred the eRapid. Mean patient-reported administration times were shorter with the eRapid vs the LC Plus (2.7 vs 10.2 min). Adverse events were similar between devices. CONCLUSIONS: Administration of dornase alfa via the eRapid nebulizer resulted in comparable efficacy and safety, shorter nebulization times, and higher patient preference.