Steroid-toxicity insights

In Conversation With… Dan Hawcutt, MD MRCPCH

Written by Steritas | Mar 13, 2024 9:43:33 AM

“The harms caused by steroids are not the most reported side effects because there is still a prevalent misunderstanding that steroid-toxicities are just a cost of doing business with steroids.”

 
Dan Hawcutt, MD MRCPCH is a reader in pediatric pharmacology at the University of Liverpool, and honorary consultant in pediatrics at Alder Hey Children’s Hospital. He is the director of Alder Hey’s early-phase clinical research facility, overseeing early-phase drug trials, and testing medicines, including steroids.

He says he “fell” into the relatively unusual subspecialty of pediatric clinical pharmacology, because of a fascination with pharmacology and a preference for pediatric medicine.


“I am pretty much agnostic from a disease perspective. I’m more interested in balancing the risks, harms and benefits of medications, and these are typically understudied in pediatric medicine.


There are some areas of pediatrics where steroid reduction is done reasonably well, such as rheumatology, but there are some areas where it's not - particularly in areas where there are currently no licensed alternative therapies.”

 

Dr Hawcutt first became interested in steroids when he was asked to support a pediatric clinical trial by the Department of Health chair of pharmacogenomics. The trial was designed to investigate the pharmacogenetics of children using steroid inhalers to identify which patients were susceptible to adrenal suppression, and which weren't.

 

“There are a multitude of pharmacogenomic studies looking at the efficacy of various asthma treatments, but so far there have only been one or two studies into the harms of steroids. 


We have access to an array of asthma drugs that work through different mechanisms and come with different side effect profiles and what appear to be fairly distinct efficacy profiles. Asthma should provide the perfect case study of how to create a pharmacogenomic map and personalize treatment. 


We should be able to combine these data to come up with personalized treatment plans for patients. As soon as someone has an asthma attack and receives a blue (salbutamol) inhaler, we should be able to create a personalized plan for what happens if you have an exacerbation based on the patient's pharmacogenomic risk-benefit profile.”

 

According to Dr Hawcutt, steroid-toxicities are observed in two very different pediatric populations, a small population of pediatric patients where high-dose steroids are needed for prolonged periods, and a very large population where low levels of steroids are prescribed intermittently. 
 
The first group consists of young people with devastating conditions such as rheumatoid arthritis, cancer and Duchenne’s disease, where high-dose steroids are needed for prolonged periods. These patients incur typical high-dose steroid side effects such as weight gain, growth impairment, and increased susceptibility to infection.


The second group consists of pediatric patients with eczema, dermatitis and asthma. To put this in context, one in ten children has asthma. Not all of those will be prescribed steroids but this group consists of hundreds of thousands of steroid-treated children. 

 

“Steroids are one of the top two or three drugs for side effects that you could recognize. The harms caused by steroids are not the most reported side effects because there is still a prevalent misunderstanding that steroid-toxicities are just a cost of doing business with steroids. 

If a patient has leukemia and is given a massive dose of steroids as part of their treatment, they are going to gain weight, become hypoglycemic, and may develop vascular necrosis at their femoral head. But people don't distinguish the harms caused by steroids the way they probably should because the patient is already so ill, and the side effects are just expected.”

 

Dr Hawcutt explains to combat this, the MHRA and other regulatory agencies are moving towards real-world data to evaluate the efficacy of medications; however, he cautions that without careful and consistent prompting, the harms of medications can be missed.

 

“Unless you have a validated instrument such as the pGTI built into the electronic medical record system that generates mandatory fields that clinicians have to complete on prescribing medication, real-world data will never give you an accurate picture of the relative risks and benefits of different treatments.

If we could ensure standardized data collection at scale using the pGTI, it would help rationalize the prescribing advice for steroids across all sub-specialties, develop richer data sets, associate genetic polymorphisms with the risks of side effects, and build personalized treatment plans.

If personalized treatment isn’t possible, let's at least make sure you are on an enhanced monitoring plan.”

 

Dr Hawcutt is the clinical pharmacology lead for the STAR-JIA clinical trial, which has been designed to compare the effectiveness, safety and cost-effectiveness of intravenous and oral steroid regimens in juvenile idiopathic arthritis. Recruitment is taking place now in 20 sites across the UK and, as part of the trial, a biobank of samples will be collected and stored to enable future research.

 

“The primary outcome of the study is to find out which protocols work to reduce joint pain best and most rapidly. I hypothesize that massive doses of intravenous steroids will make the joints feel better faster.

I’m excited to use the Steritas pGTI to find out what the cost of these regimens are and plot not just the efficacy-dose response curves, but also the side-effect-dose curves. 

We can then go back to the families and start to offer them discrete choice experiments about the benefits and risks of each approach and start to find the best approaches for each patient.”

 

Dr Hawcutt is eager to be able to start adopting the “treat to target” concept, pioneered by Eve Smith, PhD MBCHB with lupus patients, with his pediatric patients. With “treat to target,” target levels of disease control and tolerable medication burden are agreed upon with the patient, with the realization that risks and harms are very different for a five-year-old, versus a fifteen-year-old, especially when compared to a 50-year-old.

 

“I want to be able to talk to my patients and ask, ‘How much better can we make you feel and how hard can we push to get you there?’ For me, this is about personalizing the goals of treatment - both the target benefits and target harms we are willing to accept to get to the benefits.”

 

 
Dr Hawcutt is a reader in pediatric pharmacology at the University of Liverpool, and honorary consultant in pediatrics at Alder Hey Children’s Hospital. He is director of research at Alder Hey Children's Hospital, and director of the NIHR Alder Hey Clinical Research Facility (CRF). Dr Hawcutt is also chair of the Royal College of Paediatrics and Child Health (RCPCH) / Neonatal and Paediatric Pharmacists Group (NPPG) joint standing committee on medicines, and a member of the Medicines and Healthcare Regulatory Agency Pharmacovigilance Expert Advisory Committees on both Pharmacovigilance and Paediatric Medicines. In addition, he is chair of the RCPCH training committee for Paediatric Clinical Pharmacology.