Switching from originator recombinant growth hormone (Genotropin™) to biosimilar (CRISCY™): Results from a 6-month, multicentric, non-inferiority, extension trial.

OBJECTIVE: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm. DESIGN: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). RESULTS: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group. CONCLUSIONS: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch.

Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial.

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

Diagnóstico de diabetes gestacional / Diagnosis of gestational diabetes

No disponible

Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes.

OBJECTIVE: Our goal was to compare sensitivity, specificity, and predictive values of glucose and cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF)] in amniotic fluid (AF) to detect an AF-positive culture. METHODS: Amniocentesis was performed on 113 patients with preterm labour (PTL) and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria, and for mycoplasmas. AF analysis included cytokines and glucose determinations. RESULTS: The prevalence of positive AF cultures was 11.5% (13/113). Anaerobic bacteria were isolated in 9 patients (69.2%). The glucose <16 mg/dl and cytokines values; IL-1 >640 pg/ml, IL-6 >55,000 pg/ml, IL-8 >1,000 pg/ml, TNF >672 pg/ml, were significantly correlated (P < 0.01) with AF culture result. Glucose had a sensitivity of 69.2% and a specificity of 96% for the prediction of positive AF culture. The sensitivity and specificity of the cytokines ranged from 61.5-53.4% and 79.8-8.99%, respectively. CONCLUSIONS: In the diagnosis of the AF-positive culture, glucose <16 mg/dl is more sensitive than cytokines.

Phenotypic analysis of yellow fever virus derived from complementary DNA.

A thorough phenotypic characterization of yellow fever (YF) virus generated from cDNA is a necessary prerequisite for mapping virulence/attenuation determinants and exploring the potential of YF attenuated virus 17D as a carrier for heterologous protective epitopes. In this study, YF virus was produced from 17D cDNA clones after lipofectin-mediated RNA transfection of certified primary cultures of chicken embryo fibroblasts (YFiv5.2/SL). This virus was passaged once in embryonated chicken eggs according to current YF vaccine manufacture methodology to produce the experimental virus (YFiv5.2/VL). These viruses were characterized in established monkey neurovirulence safety tests and quantitative clinical and histologic scores were derived for each virus. The experimental vaccine viruses (YFiv5.2/SL and VL) compared favorably with another well-known YF vaccine strain (17DD) used as control virus for the histologic score. Although slightly higher clinical neurovirulence was observed for YFiv5.2 as compared with the 17DD virus, it should not preclude the use of YFiv5.2 for mapping YF virus virulence determinants.

Nail-patella syndrome and pre-eclampsia.

We present here the first described case of Nail-patella syndrome (NPS) and pregnancy. Complications occurred during the pregnancy with the onset of preeclampsia at 22 weeks, leading to intrauterine fetal death at 24 weeks. The nephropathy of the NPS began clinically during the course of gestation. Postpartum, it persisted as isolated proteinuria, which became a nephrotic syndrome 18 months later.

Serum fructosamine is not a useful screening test for gestational diabetes.

Serum fructosamine was measured in 569 samples of pregnant women without gestational diabetes. We defined abnormal fructosamine as mean + 2SD, and analysed its potential value to detect patients with gestational diabetes diagnosed with current screening criteria. We found serum fructosamine to be an insensitive parameter: Measured at the time of a positive 50 g glucose screening, SF would have detected 4/48 gestational diabetes.

Conservative treatment of intrapartum fetal acidosis with a betamimetic agent.

553 cases of intrapartum fetal acidosis (pH less than 7.25) were treated with a betamimetic agent (ritodrine 250-300 micrograms/min). In 403 cases (72.8%), an improvement of fetal pH greater than 0.05 pH U was observed. Improvement was comparable in cases where the cause of fetal distress was abnormal uterine activity and in those where this was not the cause. Indeed, the recovery rate was the same, independent of the percentage of uterine activity inhibition. The neonatal condition was better in the pH recovered versus not recovered group. We suggest that conservative treatment of fetal distress with betamimetic drugs is a reasonable measure for improvement of fetal and neonatal condition.

Long-term hospitalization and beta-mimetic therapy in the treatment of intrauterine growth retardation of unknown etiology.

A group of 98 third trimester pregnant women whose ultrasonographic studies raised the suspicion of intrauterine fetal growth retardation was studied. The patients were randomly assigned to two groups: Group A (Treatment group: 44 patients) and Group B (Control group: 54 patients). All patients were admitted to the hospital upon diagnosis for baseline evaluation. Those in Group A remained in the hospital until delivery (mean stay 15 +/- 5 days) and received treatment with 10 mg/t.i.d. of p.o. ritodrine. Group B patients were discharged after an average stay of 7 +/- 3 days. This group was not treated with ritodrine, and they were seen weekly in an outpatient setting. The prevalence of low-birth-weight infants for their gestational age was 47.73% in the treatment group and 40.74% in the control group. Of the deliveries in the treatment group, 40.9% were induced (half for fetal indications). In the control group 35.18% of the induced labors was (47.35% for fetal indications). Of the cases in the treatment group 18.18% were delivered by cesarean section, of which 62.5% were performed for fetal distress. The control group showed similar figures: 16.66% cesarean sections with 77.7% of them done for fetal distress. We observed an incidence of 20.45% of acute fetal distress in the study group against 12.96% in the control group. Such a difference is not statistically significant. The group under study demonstrated a rate of 6.82% pathological pH value in the umbilical artery, while the rate of abnormal values in the control group was 18.52%. In both groups, the greatest percentage of acidotic pH was observed in patients with IGR.(ABSTRACT TRUNCATED AT 250 WORDS)