Steroids vs. Steroid-Sparing Treatments
In the 1950s, scientists made an enormous medical discovery: corticosteroid medicines, which mimic the body’s stress hormones, could help reduce the symptoms of inflammatory conditions and suppress the immune system. This would enable them to fight diseases where the immune system mistakenly attacks its own tissues, such as rheumatoid arthritis, multiple sclerosis, vasculitis and lupus. The advent of corticosteroid medicines in the 1950s led to Nobel prizes in medicine and physiology, and offered enormous relief to people suffering from these severe inflammatory diseases.
While corticosteroid medicines are useful in treating many kinds of diseases, they also carry an array of potential side effects, such as fluid retention, bone damage, elevated blood sugars, and problems with mood, memory, and mania. In some clinical situations, the risks of corticosteroids outweigh the benefits of the treatment, particularly when high doses are required for a prolonged period of time, which is why many physicians and investigators are now focusing on “steroid-sparing” treatments, to help minimize these effects.
“Corticosteroids are like the oncology equivalent of chemotherapy,” says Paul Brunetta, Principal Medical Director and Global Head of Anti-CD20 Immunology at Genentech. “They’ve been around a long time, and have a use. But increasingly, over time, we want more options that may have less toxicity.”
Today, physicians across multiple specialties have the goal of tapering the use of corticosteroids, or getting their patients off steroids completely. There are an increasing number of therapies that help reduce the required therapeutic dose of steroids, including new biologic drugs that moderate the immune system. But until recently, there was no tool investigators could use in clinical trials that effectively measured the negative impact of steroid use.
To help measure the relationship between steroid use and adverse side effects, Genentech, along with a group of independent investigators, has developed an instrument called the Glucocorticoid Toxicity Index (GTI). This is an instrument that can be used in clinical trials to assess steroid toxicity. “This kind of instrument has never been developed before,” says Brunetta. The tool can be used across many diseases, tracking the relationship between steroid exposure and an adverse event. The GTI quantifies adverse steroid effects in nine different domains, including body mass index, glucose tolerance and skin reactions. He went on to add, “This tool helps investigators understand whether a side effect is likely caused by steroids.”
The GTI will give investigators the first sensitive tool to use in randomized trials to measure whether a reduction in steroids leads to less steroid toxicity. Right now, they are beginning to use the GTI in several clinical trials. To help clinical investigators and eventually physicians in clinical practice, the GTI team is looking to develop an app so that the instrument is accessible on a mobile platform. They are also developing a pediatric version of the GTI, since steroid side effects are different in young patients. A future app may allow patients to report their own adverse events.
“Steroid toxicity is an issue that is important across many different diseases and across multiple drugs,” says Brunetta. “We’re going to hear a lot more discussion about steroid-sparing or steroid avoidance in the future.”