Introduction: Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). Objective: To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. Methods: Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, n = 67) with ≥4 years' height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. Results: The mean (SD) baseline age was 8.38 (3.57) years; HSDS, -2.76 (1.03); GH dose, 41.6 (11.1) μg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was -1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was -1.51 (0.60) (154.90 [3.21] cm) in females and -1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ -2. Adverse drug reactions and GH-unrelated serious adverse events (n = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. Conclusions: GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ -2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.
Bibliographical noteFunding Information:
Tilman R. Rohrer has acted as a consultant for Novo Nordisk and received speaker honoraria from Novo Nordisk. M. Jennifer Abuzzahab has received research grant/research support from As-cendis, Astra Zeneca, Levo, Millendo, Novo Nordisk, Rhythm, and Soleno. She has attended advisory boards for Ascendis and Rhythm and speaker’s bureau for Novo Nordisk, Rhythm, and Sandoz. Philippe Backeljauw has received research grant support from Novo Nordisk, Opko, and Ipsen and is a consultant for Novo Nordisk, Ipsen, Sandoz, and Endo Pharmaceuticals. Anna Camilla Birkegård, Vlady Ostrow, and Alberto Pietropoli are employees of Novo Nordisk. Jo Blair has acted as a consultant for Novo Nordisk, has received speaker honoraria from Novo Nordisk and Sandoz, and has received financial support in the form of registration fees from Novo Nordisk to attend academic meetings. Jovanna Dahlgren has received honoraria from Merck, Novartis, and Pfizer, as well as unrestricted grants from Pfizer for 2 clinical trials. Petur B. Juliusson has received a lecture fee from Novo Nordisk for a presentation at a Novo Nordisk meeting. Michel Polak is a member of the Increlex European registry and Novo Nordisk growth international advisory board and has institutional disclosures from Pfizer France. He has received grants from Ipsen, Novo Nordisk, Pfizer, Lilly, Sanofi, Sandoz, and Merck and government grants (PHRC, PHRIP, and ANR). Alicia Romano has been a consultant for Ascendis Pharma and is a consultant and speaker for Novo Nordisk. Judith Ross is a consultant for Novo Nordisk and Opko and receives research funding from Novo Nordisk. Lars Sävendahl has received consultancy fees from Ascendis, Hexal, Novo Nordisk, Merck, Pfizer, and Sandoz. Bradley S. Miller has been a consultant for Ascendis, BioMarin, Bluebird Bio, Gene-Science, Novo Nordisk, Pfizer, Sandoz, Sanofi Genzyme, Soleno, Takeda, Tolmar, and Versartis and has received research support from AbbVie, Alexion, Ascendis, Novo Nordisk, Opko, Orphan Reach, Sandoz, Sangamo, Sanofi Genzyme, Takeda, and Versartis in the last 3 years.
The authors would like to thank the patients, their families, the nurses and study coordinators, and all investigators involved in this study. Statistical support was provided by Jean-Marc Ferran (Qualiance ApS) and Moshe Fridman (AMF Consulting), both under contract to Novo Nordisk A/S. Medical writing and editorial support were provided by Penny Butcher, PhD, and Helen Marshall of Watermeadow Medical, part of the Ashfield Group, supported by Novo Nordisk Health Care AG. The sponsor was involved in the study design and collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. This work was dedicated to the memory of Dr. Jacqueline Noonan (1928–2020).
© 2020 The Author(s) Published by S. Karger AG, Basel.
- Growth hormone therapy
- Near-adult height
- Noonan syndrome
- Ras/mitogen-activated protein kinase
- Real-world evidence
PubMed: MeSH publication types
- Journal Article