“Steroids have a role in treating so many diseases - and yet, they do not cure any of them.” 

John H. Stone, MD MPH is a Professor of Medicine at Harvard Medical School, and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital. He is the inventor of the Glucocorticoid Toxicity Index (GTI) family of clinical outcome assessment instruments and the chair of the Steritas Scientific Advisory Board. He is also the editor of the much-loved book, A Clinician’s Pearls and Myths in Rheumatology.

As a young resident physician, Dr Stone was initially torn between becoming an infectious disease specialist and supporting the fight against HIV/AIDS and rheumatology, which he describes as, “diseases in which the immune system becomes confused and different immune cells start to attack the patient's own body.”

However, witnessing his mother pass away from an autoimmune disease known as scleroderma, an event he describes as “cataclysmic,” as well as his interactions with other rheumatology patients made him realize his calling was to be a rheumatologist.

“We have enormous progress in the rheumatic diseases over the past 30 years, but sadly the one disease where we really have not made much progress is scleroderma, where we still have a long way to go, although I am encouraged by some therapeutic approaches I see on the horizon.”

Despite the progress made with the development of biologic agents that target diseases more effectively, Dr Stone cautions that all too often clinicians rely on glucocorticoids as a mainstay of treatment.

“Steroids are rheumatology’s dirty little secret. And they're also the dirty little secret for gastroenterology and for dermatology and for neurology and nephrology and pulmonary medicine. Although we have designed successful trials that demonstrate steroid-sparing effects of some medications, in routine clinical practice steroid use is still ubiquitous and excessive.

The epidemiologic studies that have examined practice patterns very clearly show that arthritis patients who are treated in clinical practice, as opposed to a clinical trial, receive twice the amount of steroids over the same period of time as patients who might be enrolled in a trial.”

Even with considerable progress in the development of new therapies, he cautions that there’s no real sign that steroid use is declining, and highlights that several recent studies show that usage is actually on the rise.

“Clinicians were trained to prescribe steroids, and they are a knee-jerk response for so many different conditions because we know there is no therapy that achieves swifter disease control. They're a nice safety net because we know that they work, but it's challenging to get patients off of them. So in that way, they can actually be like opioids.

One of the reasons it's difficult to get patients off of steroids is that we know that when we stop them, very often disease flares occur. Steroids have a role in treating so many diseases - and yet, they do not cure any of them.”

Another challenge Dr Stone highlights is one of awareness, either of the insidious nature of the build-up of steroid-toxicity or the availability of newer steroid-sparing therapies that can be prescribed for conditions that primary care clinicians do not often see in routine care.

He also details that while the side-effects are very expensive, glucocorticoids are cheap to prescribe, especially in comparison to the cost of newer medications that may require busy clinicians to work through bureaucracy to encourage payors to allow them to be prescribed - all while the patient is suffering.

“All too often, the physician and the patient strike a Faustian bargain when they agree to have short-term beneficial effects of steroids, in return for long-term toxicity.”

When asked about the issues he raises with patients when prescribing steroids, Dr Stone says he has a series of items he raises with them, including both the positives about how they control inflammation very quickly, but also that they have a lot of side effects.

“I do have to acknowledge that like many of my colleagues, during routine clinic I don't have adequate time to consent patients fully to all the things that might happen as there are just too many. There are as many as 70 or 80 well-known steroid-toxicities, and that explains why measurement has historically been so challenging.

What is shocking is that currently, there isn't a single resource for us to share with patients about these side effects. We put patients on these powerful, potentially dangerous medications for many months. We tell them a few things about them in the clinic, but there is no detailed literature for patients, not even a well-developed website.”

Over the past few years, Dr Stone has spent much of his research developing a suite of clinical outcome assessment instruments for measuring steroid-toxicity with the help of subspecialty experts from around the world.

“The challenge of measuring and monitoring steroid-toxicity was so great that I convened a group of well-respected subspecialty experts to develop the Glucocorticoid Toxicity Index. It was a tremendous collaboration featuring Zoom calls and a day-long meeting in San Francisco just before the ACR meeting in 2016. All of the collaborators worked really hard to develop a validated measure of steroid-toxicity.

Many of the collaborators have continued to push this mission forward very actively. Frank Buttgereit from Charite Hospital in Berlin, for example, just visited me this week to collaborate on the impact of glucocorticoid toxicity on bone. Liam Heaney's group of pulmonologists have used and published on the GTI in a longitudinal cohort of asthma patients in Belfast, and Dedee Murrell has used the GTI with another international group of dermatologists, publishing several papers on autoimmune blistering diseases. All of this just helps the effort go from strength to strength.”

Dr Stone and Steritas have seen a fantastic response to the GTI from academic investigators and pharmaceutical researchers. 

“Pharma has been one of our most powerful allies, and I truly enjoy the interactions and collaborations we've developed. We are natural allies, and colleagues in industry have helped us develop in important directions - not only in the area of supporting clinical trials to help bring new therapies to market, but also helping to figure out how to make the case for steroid-toxicity reduction to payors and how to develop instruments for the purpose of educating patients. It has been refreshing to see so many early adopters and to gather new ideas from these interactions.”

Those efforts have seen the GTI family expand with the addition of the pediatric GTI (pGTI), which provides a systematic approach to assessing steroid-toxicity in children between the ages of 2 and 18 years, and a clinical version of the GTI, the GTI-MD, that is easy to integrate into existing clinical workflows. 

“It's very clear that being able to measure things is essential if we want to change them. And with the suite of clinical outcome assessments, the GTI, pGTI and now the GTI-MD, we can measure steroid-toxicity not only in clinical trials but in clinical practice as well. 

We can interrogate large databases to ask intelligent questions about the impact of steroid-toxicity using data that's already been collected. With the GTI-MD, we can review that data and understand what the implications of steroids are over a 10-year period. Patients could soon be able to measure their own steroid-toxicity. 

Ultimately, this information is very important for discussions with payors to help them identify when and why new treatments should be made available to patients.”