“I think we have a real problem in how we deliver steroid reduction, and that in part is due to the complexity of constantly changing doses.”
David Jayne, MD is a clinical nephrologist at Addenbrooke's Hospital, Cambridge UK where he directs a severe inflammatory disease service that has assessed and cared for over 5,000 patients, mainly with vasculitis and lupus, over the last 20 years. He is the founder and President of the European Vasculitis Society and a founding member of the Lupus Nephritis Trials Network.
As a young physician, he was fascinated by the technologies used to manage kidney failure and looked after several patients with severe forms of vasculitis and lupus whose kidneys had been severely impacted by these conditions. He was then invited to join a research program studying the diseases and that was where his passion for helping these patients really took off.
Thanks to the therapeutics that have been developed over the past 70 years, from glucocorticoids to modern immunomodulators, patients with lupus and vasculitis have a much-improved prognosis. However, patients with renal diseases still have increased risks of cardiac disease caused, in part, by factors such as hyperlipidemia, hyperglycemia and hypertension – all of which are exacerbated by glucocorticoids.
“If we have a recently diagnosed vasculitis or lupus patient with severe symptoms, we need to quickly bring the inflammation under control – often using high-dose steroids.
We increasingly worry about how to protect our patients from cardiovascular disease, especially as causes such as hyperlipidemia, and hypertension, and hyperglycemia are all exacerbated by steroids. There are a number of new non-steroid therapies which do reduce cardiovascular risk, and help patients avoid steroids – which is a really big benefit of these treatments – but they still often are used as a second-line treatment, once the initial disease flare is brought under control.”
While Dr Jayne applauds the positive impact that short-term steroid treatments can have, he is very conscious of their side effects.
“The impact of steroid-toxicity is huge – for example. In ANCA-associated vasculitis, infection is the major cause of death in the first year after diagnosis, and steroids are the major modifiable factor that impacts the risk of infection. If you look at irreversible tissue damage after five years, steroid-related damage rivals the damage that would have been caused by the disease itself.”
This poses a real challenge to clinicians, who need to reassure the patient that they are on the right treatment pathway, but also that the pathway they are on needs to navigate a complex set of changes once the condition is under control.
“Newly diagnosed patients are very motivated to get better, but they are often scared and not in a good frame of mind to receive a lot of complicated information about the short and long-term adverse effects of therapy.
What we normally do when we're starting high-dose steroids is to warn them about the short-term effects, particularly insomnia and psychological effects, because a minority of patients get a very bad psychological reaction, which can be very scary, we also warn carers and family members so they can cope better if, or when they occur. But it is a delicate balance because you don’t want to overload patients at a time when they're not really able to process the data and you don’t want to scare them off the treatment that will save their lives.”
Dr Jayne highlights one of the key challenges faced by clinicians, regulators and payers is that steroid-toxicity has been an understudied area, making the risk-benefit assessment of treatments for patients particularly challenging.
“Steroid-toxicity has historically been poorly assessed, but the Glucocorticoid Toxicity Index (GTI) changes this by enabling the objective assessment of toxicity in different treatment groups in clinical trials.
While its use in routine clinical practice outside trials is less developed, if we did use the GTI in more routine clinical settings, we might take a more holistic view of toxicity rather than focusing on just a few markers such as metabolic bone disease or hyperglycemia. There's certainly a movement towards annual reviews where you look at lipids, blood pressure, and cardiovascular risk factors – and that would be a good opportunity to assess the patient using the GTI. I've no doubt that the GTI would turn out to be predictive of a number of outcomes, including cardiovascular outcomes, which would be a big step forward for patient care.”
He believes having a measure such as the GTI may also help clinicians reduce steroid dosage, and therefore damage, especially those that are less experienced at delivering a steroid taper.
"I believe we could deliver steroid reduction protocols better in routine practice. We know what dose we want to start at and end at, but in the rough and tumble of normal practice, very few patients actually follow what would be a rigid step-down regimen that you would find in a clinical trial.
We tried to translate some of our learnings from clinical trials such as giving patients the regimen printed out so they know exactly how much they're taking on which day – but it's very complex as you're constantly changing the dose every day.
Less experienced clinicians tend to be very concerned about reducing steroid doses – with the tendency to keep people on too high a dose for too long. More experienced physicians are usually happier about bringing the dosage down.”