Long-Term Velaglucerase Alfa Treatment in Children with Gaucher Disease Type 1 Naïve to Enzyme Replacement Therapy or Previously Treated with Imiglucerase

Background Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). Methods Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30–60 U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. Results The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for \u3e 30 months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8 years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24 months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. Conclusion The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults

Personality and Temperament Correlates of Pain Catastrophizing in Young Adolescents

Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of the behavioral inhibition and behavioral activation systems (BIS-BAS), and various reactive and regulative temperament traits. Results demonstrated that BIS, reactive temperament traits (fear and anger-frustration), and perceptual sensitivity were positively related to pain catastrophizing, whereas regulative traits (attention control, inhibitory control) were negatively associated with this cognitive factor. Further, regression analyses demonstrated that only BIS and the temperamental traits of fear and perceptual sensitivity accounted for a unique proportion of the variance in adolescents’ pain catastrophizing scores

Lumbar muscle dysfunction during remission of unilateral recurrent nonspecific low-back pain: evaluation with muscle functional MRI

Objectives: After cessation of a low back pain (LBP) episode, alterations in trunk muscle behavior despite recovery from pain have been hypothesized to play a pathogenic role in recurrence of LBP. This study aimed to identify the presence of lumbar muscle dysfunction during remission of recurrent LBP, while performing a low-load trunk extension movement. Methods: Thirteen participants with unilateral recurrent LBP were tested at least one month after cessation of the previous LBP episode and were compared to a healthy control group without any history of LBP (n=13). Also, differences between previously painful and non-painful sides were examined. Muscle functional magnetic resonance imaging (MRI), based on quantitative T2-imaging, was used to examine muscle tissue characteristics (T2-rest), and muscle recruitment (T2-shift) during prone trunk extension. The lumbar Multifidus (MF), Erector Spinae (ES), Quadratus Lumborum (QL) and Psoas (PS) were bilaterally visualized on 2 lumbar levels using a T2-weighted (spin-echo multi-contrast, SE_MC) MRI-sequence. Results: Linear Mixed Model analysis revealed a significantly lower T2-rest (p=0.044) and a significantly higher T2-shift (p=0.034) solely for the MF in the LBP group compared to the control group. No significant differences between pain-sides were found. Discussion: Lower T2-rest values have been suggested to correlate with a conversion of the MF fiber typing towards the glycolytic muscle spectrum. Elevated T2-shifts correspond with increased levels of metabolic activity in the MF in the LBP group, for which several hypotheses can be put forward. Taken together, these findings provide innovative evidence of concurrent alterations in Multifidus structure and activity in individuals with unilateral recurrent LBP, despite being pain-free and functionally recovered

Safety and Efficacy of Long-Term Velaglucerase Alfa Therapy in Treatment-Naïve Adults with Type 1 Gaucher Disease: Results from Phase III Trials

A subgroup analysis of the safety and efficacy of velaglucerase alfa in adult patients (age ≥ 18 years) with type I Gaucher disease (GD1) who were treatment-naïve at advent of trial participation is presented