Safe & Effective Hormone Therapy for Turner Syndrome Patients

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The Turner Syndrome Foundation (TSF) is a strong advocate for early diagnosis. Diagnosing Turner Syndrome (TS) early is critical, in part, because it allows for timely and effective growth hormone therapy (GHT) treatment for TS patients. Read below about one important study of a GHT treatment.

The Importance of Early Diagnosis

TS is a chromosomal condition that affects 1 in 2,000 female births. TS causes a partially or completely missing X chromosome. This chromosome holds DNA–the building blocks of cell function–that helps develop various organs like the ovaries and immune system. Patients with TS can have various physical, mental, and social challenges. 

Since this condition is not well known, early diagnosis is rare, but it helps:

  • give growth hormone and/or hormone replacement therapy (GHT and HRT) enough time to improve the health and height of patients with TS; and
  • make potentially lifesaving medical interventions for heart and other health challenges possible, preventing them from developing into dangerous problems.

It is important for both doctors and patients to spread TS awareness. 

"I believe in innovation, and that the way you get innovation is you fund research and you learn the basic facts."

Bill Gates

Growth Hormone Study

This post discusses a recent research study published in August 2021 about a type of growth-hormone therapy called Omnitrope, a recombinant human growth-hormone (rhGH) therapy. This type of therapy is created by using bacteria to copy human growth hormone DNA and administering it to patients. The study’s discoveries are causing doctors to consider Omnitrope as a more affordable, effective and thus accessible alternative to other GH therapies.

Note: Please see the Glossary below for an explanation of some of the terms in this article.

Purpose

This is what Omnitrope looks like, courtesy of HGH Vallarta.

For over two decades (since 1996), rhGH has been approved to help the TS community overcome height-and growth-related challenges. Various clinical trials have shown rhGH’s overall effectiveness and safety with helping to improve the adult height of patients with TS. However, its effectiveness varies, based on when patients start their treatment, the doses they take, their weight, and other factors.

Omnitrope, a biosimilar rhGH therapy, was approved in 2006 by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

The international and observational study, PAtients TReated with Omnitrope (PATRO) Children, reviews the safety and effectiveness of this drug in all areas of pediatric patients using data from the PATRO study.

Researchers

This project’s researchers included: 

  • Philippe Backeljauwa, from the Cincinnati Children’s Hospital Medical Center in Ohio;
  • Shankar Kanumakalab, from the Royal Alexandra Children’s Hospital in Brighton, UK;
  • Sandro Lochec, from the Hospital for Children Microcitemico “A. Cao” in Cagliari, Italy;
  • Karl Otfried Schwabd, from the Pediatric Department at the University Medical Center in Freiburg, Germany;
  • Roland Werner Pfäffle, from the Pediatrics Department at the University of Leipzig in Germany;
  • Tadej Battelinoi, from the University Medical Centre-University Children’s Hospital’s Paediatric Sector, Endocrinology, Diabetes, and Metabolic Diseases Department, at the University of Ljubljana in Slovenia;
  • Tomasz Giemza, from Sandoz Poland in Warsaw; 
  • Hichem Zouater, from Sandoz GmbH in Holzkirchen, Germany;
  • Elena Lundberg, from the Pediatrics Division’s Institute of Clinical Science at Umeå Uiversity in Sweden;
  • Berit Kriström, from the Pediatrics Division’s Institute of Clinical Science at Umeå Uiversity in Sweden; and
  • Charlotte Höybyef, from the Endocrinology Department at Karolinska University Hospital in Solna, Sweden, and Karolinska Institute’s Department of Molecular Medicine and Surgery in Stockholm.

Scope & Funding

The study sample included 348 infants, children, and adolescents with TS who received at least one dose of Omnitrope. As of August 2019, they were from 130 medical centers in various countries. Of these 348 patients, 163 participated in the GH therapy effectiveness test for three years.

The PATRO Children Study was funded by Sandoz Biopharmaceuticals and HEXAL AG, a drug manufacturer owned by Sandoz.

Conduct of the Study

The researchers conducted the observational, long-term study in the following manner:
  • For monitoring safety, all adverse symptoms in patients receiving Omnitrope were monitored and recorded in electronic case report forms (eCRFs) until August 2019. Data management then reviewed these forms to identify inconsistencies. 
  • A contract research organization performed centralized data monitoring.
  • To monitor the therapy’s effectiveness, researchers recorded several factors of height development during each child’s visit. Some factors included height velocity (HV), height standard deviation score (HSDS), height velocity SDS (HVSDS)and body mass index SDS (BMI SDS)
  • The effectiveness tests included 163 patients. These patients continually had their height measured over three years, while they were taking GHT at least once 60 days after starting it.
  • The study was discontinued for a patient if they reached their target adult height.
  • Finally, data analysis was created by using descriptive statistics.

Safety Results

Researchers determined that the biosimilar rhGH Omnitrope is safe and effective for children with TS. 

  • The safety profile in TS patients is consistent with the geoup of PATRO children overall, which included children receiving the same treatment for conditions other than TS.
  • As of August 2019, almost 50% of the TS patients (170) experienced nonfatal symptoms during the study.
  • Many participants had serious symptoms (49/170 patients), with the most serious reported symptom being intracranial hypertension. Despite this, the study doesn’t support the theory that GH therapy increases the risk of serious health challenges like intracranial hypertension and scoliosis.
  • Other patients reported mild to moderate symptoms (25/170 patients).
  • There was no evidence of an increased risk of unexpected adverse effects (AEs) or new malignancies observed in the study.

Effectiveness Results

  • Biosimilar rhGH therapy did increase the height of girls with TS.
  • Around one-third of the girls in the three-year effectiveness group reached their target adult height.

Limitations

Limitations of this study included: 

  • The approved starting dose for rhGH in TS patients in Europe is 45-50 ug/kg per day and in the U.S. 50-54 ug/kg per day. However, in the current study, it ranged from 10-67 ug/kg per day, and the mean dose remained lower than the 2017 recommendations for TS patients.
  • Some other limitations of the study are typical of observational studies, such as potential selection bias due to the enrollment of patients from selected clinics in some countries. Each country’s clinics have management methods that differ from each other, and how clinics are run overall differ from country to country. 
  • As the source of data is from routine clinical practice, there is a risk of bias from incomplete data.
  • The study’s short treatment time reduces the results’ validity. A longer test is needed to see if these the trends in these results continue long-term.

The researchers (whose names are abbreviated below) disclosed the following conflicts of interest:

    • P.B., S.L., and K.O.S. are PATRO Children Global Steering Committee members. 
  • S.K. has been a speaker for Sandoz and is a member of the above committee. 
  • C.H. has received lecture fees from Sandoz and is a member of the PATRO Adult Global Steering Committee. 
  • T.B.’s institution has received grants from Sandoz. 
  • R.W.P. has received lecture fees from Sandoz, Merck, Pfizer, Novo Nordisk, and Ferring. He also serves as an advisory board member for the PATRO Children Study in Germany. 
  • H.Z. and T.G. are employees of Sandoz. 
  • E.L. and B.K. had no relevant disclosures to declare.

Suggestions for Future Research

  • Several AEs are observed, so there is a need for ongoing patient monitoring.
  • Optimization of rhGH dose may contribute to a higher adult height and needs further evaluation.

Importance for the TS Community

Advocating for TS awareness is important, as it equips both patients and doctors to recognize signs and receive earlier diagnoses. Thus, early detection of TS allows for GHTs like Omnitrope and other potentially lifesaving medical interventions to be utilized to their full potential. Supporting the TS community and advocating for TS awareness increase opportunities and help individuals with TS overcome their health challenges.

If you would like to help promote TS awareness, you can:

  • join TSF’s professional membership to learn how to help the TS community get the medical services they need and support them,
  • join TSF’s educator membership and check out resources to learn more about TS and the TS community and how to support students, and
  • participate in TS research or collaborate with TSF for your research project to help the TS community.

Glossary

  • Adverse effects(AE’s): the body’s harmful or abnormal reactions to medicine that you take.
  • Biosimilar rhGH therapy: rhGH therapy that uses living organisms as ingredients; not identical to its brand-name counterparts, but it is highly similar and has no meaningful clinical differences in its active components.
  • Body mass index standard deviation score (BMI SDS): measures the rate at which a patient is gaining, losing, or staying at the same weight.
  • Descriptive statistics: a set of brief descriptive coefficients that summarize a given data set representative of an entire or sample population.
  • Electronic case report forms (eCRFs): a paper or electronic questionnaire specifically used in clinical trial research to collect data from each participating patient.
  • Growth-hormone therapy (GHT): used to help patients with TS improve their height.
  • Height standard deviation score (HSDS): measures how close someone’s height is to the average range of height that most people fall into.
  • Height velocity (HV): measures how much someone’s height increases over time.
  • Height velocity standard deviation score (HV SDS): measures whether someone grows vertically at a rate that is below, at, or above average as compared to most people.
  • Hormone teplacement therapy (HRT): includes growth hormone therapy or estrogen replacement therapy to ensure that patients with TS age healthily.
  • Intercranial hypertension: a build-up of pressure around the brain.
  • Malignancies: health conditions worsening over time.
  • PAtients TReated with Omnitrope (PATRO) Children Study: multicenter, longitudinal, observational, post-marketing surveillance study.
  • Recombinant DNA: DNA constructed with bacterial enzymes, which take different parts of various people’s DNA, combine them, and then clone them for scientific use, such as GHT.
  • Recombinant human growth-hormone (rhGH) therapy: GHT that utilizes recombinant DNA.
  • Scoliosis: curving of the spine that makes it hard to breathe if not treated properly.
  • Ug: the abbreviation for micrograms.

Takeaways

  • In real-life clinical practice, the biosimilar rhGH Omnitrope is effective and well-tolerated in pediatric TS patients.
  • Since TS is diagnosed late and therefore rhGH therapy is also initiated late, many patients with TS have a reduced chance of reaching their target adult height. The delay in starting treatment after TS diagnosis should be minimized.
  • After the diagnosis of TS, starting rhGH treatment by 4-6 years of age has a better outcome.
  • Biosimilar therapies like the one discussed in the study could help lower health-care costs for some patients.

Written by Ruchika Srivastava, TSF volunteer blog writer. Edited by Prabhat Sharma, TSF volunteer blog editor, and Susan Herman, TSF volunteer lead blog editor.

Sources

Clinical

Non-Clinical

TSF Resources

 © Turner Syndrome Foundation, 2022

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