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.

Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus.

AIMS: Clinical inertia, the tendency to maintain current treatment strategies despite results demanding escalation, is thought to substantially contribute to the disconnect between clinical aspirations for patients with diabetes and targets achieved. We wished to explore potential causes of clinical inertia among physicians and people with diabetes. METHODS: A 20-min online survey of 652 adults with diabetes and 337 treating physicians in six countries explored opinions relating to clinical inertia from both perspectives, in order to correlate perceptions and expectations relating to diagnosis, treatment, diabetes complications and therapeutic escalation. RESULTS: Physicians had low expectations for their patients, despite the belief that the importance of good glycaemic control through lifestyle and pharmacological interventions had been adequately conveyed. Conversely, people with diabetes had, at best, a rudimentary understanding of the risks of complications and the importance of good control; indeed, only a small proportion believed lifestyle changes were important and the majority did not intend to comply. CONCLUSIONS: The principal findings of this survey suggest that impairments in communication are at the heart of clinical inertia. This manuscript lays out four key principles that we believe are achievable in all environments and can improve the lives of people with diabetes.

Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20-34.

BACKGROUND: A group of patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) 20-34 kg/m(2) were submitted to laparoscopic interposition of a segment of ileum into the proximal jejunum or into the proximal duodenum associated to a sleeve gastrectomy. The objective of this study is to evaluate the hormonal changes in the pre- and postoperative period. MATERIALS AND METHODS: Hormonal evaluation was done in 58 patients operated between April 2005 and July 2006. Mean age was 51.4 years (40-66 years). Mean BMI was 28.2 (20-34.8) kg/m(2). All patients had had the diagnosis of T2DM for at least 3 years. Mean duration of T2DM was 9.6 years (3-22 years). Two techniques were performed, consisting of different combinations of ileal interposition (II) associated to a sleeve gastrectomy (SG). The following hormones were assayed in the pre- and postoperative period (mean 16 months) at the baseline and following specific food stimulation (30, 60, 120 min): glucogen-like protein 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), insulin, glucagon, C-peptide, amylin, cholecystokinin (CCK), pancreatic polypeptide (PPP), somatostatin, peptide YY (PYY), ghrelin, adiponectin, resistin, leptin, and interleukin-6 (IL-6). RESULTS: Thirty patients had II associated to sleeve gastrectomy (II-SG) and 28 had II with diverted sleeve gastrectomy (II-DSG). GLP1 exhibited an important rise following the two operations, especially after II-DSG (p < 0.001). GIP also exhibited an important rise, with both II-SG and II-DSG being equally effective (p < 0.001). Insulin and amylin showed a significant rise at 30 min. Glucagon decreased slightly. CCK measurements were very low after II-DSG. PPP was also slightly altered by the II-DSG. PYY showed an important increase with both operations (p < 0.001). Ghrelin showed a significant decrease following the two operations (p < 0.001). Somatostatin and IL-6 were not affected (p = 0.632). Both leptin and resistin blood levels decreased. Adiponectin showed a slight increase. Mean postoperative follow-up was 19.2 months. Both II-SG and II-DSG were effective in achieving adequate glycemic control (91.2%). CONCLUSIONS: There was a significant hormonal change following laparoscopic ileal interposition. These alterations may explain the promising good results associated to these operations for the treatment of T2DM in the nonmorbidly obese population.

Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes mellitus.

BACKGROUND: Metabolic syndrome refers to risk factors for cardiovascular disease. Hyperglycemia is a critical component contributing to the predictive power of the syndrome. This study aimed to evaluate the results from the laparoscopic interposition of an ileum segment into the proximal jejunum for the treatment of metabolic syndrome in patients with type 2 diabetes mellitus and a body mass index (BMI) lower than 35. METHODS: Laparoscopic procedures were performed for 60 patients (24 women and 36 men) with a mean age of 51.7 +/- 6.4 years (range, 27-66 years) and a mean BMI of 30.1 +/- 2.7 (range, 23.6-34.4). All the patients had a diagnosis of type 2 diabetes mellitus (T2DM) given at least 3 years previously and evidence of stable treatment using oral hypoglycemic agents, insulin, or both for at least 12 months. The mean duration of type 2 diabetes mellitus was 9.6 +/- 4.6 years (range, 3-22 years). Metabolic syndrome was diagnosed for all 60 patients. Arterial hypertension was diagnosed for 70% of the patients (mean number of drugs, 1.6) and hypertriglyceridemia for 70%. High-density lipoprotein was altered in 51.7% of the patients and the abdominal circumference in 68.3%. Two techniques were performed: ileal interposition (II) into the proximal jejunum and sleeve gastrectomy (II-SG) or ileal interposition associated with a diverted sleeve gastrectomy (II-DSG). RESULTS: The II-SG procedure was performed for 32 patients and the II-DSG procedure for 28 patients. The mean postoperative follow-up period was 7.4 months (range, 3-19 months). The mean BMI was 23.8 +/- 4.1 kg/m(2), and 52 patients (86.7%) achieved adequate glycemic control. Hypertriglyceridemia was normalized for 81.7% of the patients. An high-density lipoprotein level higher than 40 for the men and higher than 50 for the women was achieved by 90.3% of the patients. The abdominal circumference reached was less than 102 cm for the men and 88 cm for the women. Arterial hypertension was controlled in 90.5% of the patients. For the control of metabolic syndrome, II-DSG was the more effective procedure. CONCLUSIONS: Laparoscopic II-SG and II-DSG seem to be promising procedures for the control of the metabolic syndrome and type 2 diabetes mellitus. A longer follow-up period is needed.