Some patients have sudden onset and rapid progression to death, whereas others have long-term chronic illness but few life-threatening complications. Its clinical course is highly unpredictable. The prevalence rate is 12–13 per 1,000,000 persons and is similar across sexes but higher among older adults. Although onset can occur at any age, PNH has a worldwide mean age of diagnosis of 39.3 years (SD = 18.6). If untreated, up to 35% die within 5 years of diagnosis. Such patients generally have a poor quality of life (QOL). PNH is characterized by dysregulation of the terminal complement pathway, leading to intravascular hemolysis and thrombosis. People with PNH may present with hemoglobinuria, thrombosis, impaired kidney function, abdominal pain, dysphagia, pulmonary hypertension, chest pain, dyspnea, erectile dysfunction in males, end organ damage, and/or severe fatigue. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematologic disorder with significant morbidity and premature mortality. These findings suggest that the treatments enabled adaptive changes. Significant effects of DIF by group and DIF over time support recalibration and reprioritization response-shift effects. This study revealed that people with PNH on ravulizumab or eculizumab for 26 weeks reported QOL levels better than those of the general population. DIF analyses revealed no treatment DIF, but did uncover group DIF (9 items with uniform DIF, and 11 with non-uniform) and DIF over time (7 items with uniform DIF, and 3 with non-uniform).
Results were similar for lower and higher PNH risk factors, with slightly stronger effects in the former. Ravulizumab generally showed larger effect sizes. ResultsĪcross PNH risk-factor levels, people who had been on either treatment for 26 weeks reported better-than-expected functioning and lower symptom burden compared to GenPop. Reprioritization response shift was operationalized as non-uniform DIF over time, i.e., the relative difficulty of endorsing an item over time changes across the total domain score. Recalibration response shift was operationalized as uniform DIF over time, reflecting the idea that, for a given group, the difficulty of endorsing an item changes over time, after adjusting for the total subscale score. DIF analyses examined 24 items from scales with at least two items.
Differential item functioning (DIF) analyses examined whether item response varied systematically (1) by treatment, (2) compared to GenPop, and (3) over time, the latter two suggesting and reflecting response-shift effects, respectively.
Risk-factor groups were created based on clinical indicators known to be associated with worse PNH outcomes, and separate MANCOVAs were computed for lower- and higher-risk-factor groups. Multivariate analysis of covariance (MANCOVA) investigated function and symptom scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 of people with PNH as compared to GenPop, after covariate adjustment.
#Paroxysmal nocturnal dyspnea trial
This secondary analysis compared PNH trial participants after 26 weeks on either treatment (n = 438) to a general-population sample (GenPop) (n = 15,386) and investigated response-shift effects. Clinical trials (NCT02946463 and NCT03056040) comparing ravulizumab with eculizumab for PNH have supported the non-inferiority of the former and similar safety and tolerability. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening intravascular hematologic disorder with significant morbidity and premature mortality.
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