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.

The evolution of Graves' ophthalmopathy during treatment with antithyroid drug alone and combined with triiodothyronine.

We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.