ESPE Abstracts

Background: In the European Union, Increlex^® (mecasermin) is approved for the treatment of growth failure in children with severe primary insulin-like growth factor-1 deficiency (SPIGFD).

Methods: The European Increlex^® Growth Forum Database (EU-IGFD) registry (NCT00903110) is an ongoing, multicentre, open-label, observational study monitoring the safety and efficacy of mecasermin in children in the clinical practice setting. Here we present baseline characteristics and exposure data for each participating country.

Results: As of 9 October 2018, 280 patients were screened from 10 countries, and recruitment as a proportion of the study population was highest in Germany and France: Germany (31.4%, n=88), France (23.6%, n=66), Spain (12.1%, n=34), UK (11.1%, n=31), Italy (10.4%, n=29), Poland (5%, n=14) and 'Other' countries (Sweden, Austria, Belgium and the Netherlands; 6.4%, n=18). The most frequent diagnosis was SPIGFD (244/280 patients [87.1%]; less frequent in France [68.2%] and Spain [73.5%] than Germany [97.7%] and UK [100%]). Laron syndrome was present in more patients in UK (35.5%) and Italy (34.5%) than in France (6.1%), Germany (3.4%) and Poland (0%). Mean age at first mecasermin intake was similar between countries (range: 8.59 ±4.36 years [Spain] to 9.87 ±3.65 years [Germany]). Mean height standard deviation score (SDS) ±SD at first mecasermin intake was lowest in the UK (-4.75 ±1.02) and highest in 'Other' countries (-3.15 ±1.00). Patients from Poland and Germany were less likely to have received previous growth therapy (100% and 79.5% naïve patients, respectively, vs. 60.6%, 58.8%, 64.5%, 56.0% and 55.6% in France, Spain, UK, Italy and 'Other' countries, respectively), and treatment-naïve pre-pubertal status varied between countries (from 91.7% in Poland to 41.7% in Italy). Therapy was discontinued because adult height was achieved in 5.9%, 23.1%, 31.7%, 36.4%, 38.9%, 40.0% and 44.4% in France, Spain, Germany, UK, Italy, Poland and 'Other' countries, respectively. The median dose of mecasermin at baseline was 40 µg/kg/BID in all countries. Median dose was titrated up to 120 µg/kg/BID after 12 months in Germany and France, but was more slowly titrated in other countries. Median (95% CI) treatment duration was longest in Poland (5.28 [2.37, 7.21] years) and shortest in France (1.92 [1.21, 2.46] years).

Conclusions: Aetiology, previous growth therapy, treatment duration, and titration rates of the mecasermin dose varied across European countries. International collaboration is needed to ensure a consistent approach to the identification and management of rare growth diseases such as SPIGFD.