"Trial sponsors have a great opportunity and challenge to demonstrate what they mean by steroid-sparing and how that translates into healthcare benefits such as reduced hospitalizations, and improved quality of life.“

Sudhakar Sridharan MD is a board-certified rheumatologist serving as Vice President in Medical Science & Strategy Division at PPD/ThermoFisher in the Immunology/Rheumatology/Inflammation therapeutic area at the global contract research organization PPD. He gained experience as a clinical rheumatologist at the Cleveland Clinic before moving to Wyeth Pharmaceuticals (now part of Pfizer), where he oversaw the progression of therapeutic candidates in the inflammation therapeutic area.

He has extensive knowledge of study design in immunology, trial endpoints, biomarker development, and the regulatory landscape, including participating in FDA meetings for defining key efficacy endpoints, and providing input into EMA regulatory guidance documents. 

During his time at the Cleveland Clinic, he took care of many patients with significant autoimmune disorders that required immunosuppressive medications. Dr. Sridharan's perspective based on his experience is;

“Steroids are life-saving medications in the treatment of patients with organ-threatening or, in some instances, even life-threatening conditions that require immediate intervention. They are very potent, and very rapidly acting therapeutic agents.

Usually, patients respond quickly, and they go into remission within a month or so. And then they have to be on chronic long-term maintenance doses of glucocorticoids and that is where the problem begins - you are now dealing with the effects of long-term or medium-term use of glucocorticoids.

Clinicians try to reduce steroids as quickly as possible to ameliorate or prevent the well-known but serious side effects of steroids. Many, if not all the drugs that we use these days in immunology, are an effort to prevent the long-term consequences of steroid therapy. We have had lots of success in diseases like rheumatoid arthritis where we don't use steroids for the long-term very much anymore, but in other diseases such as vasculitis and lupus, we are still developing steroid-sparing therapies.”

Since joining the pharmaceutical industry some 20 years ago, Dr Sridharan has designed and led clinical trials for many different sponsors in the field of immunology and has been inspired to improve patient outcomes by working to ensure new steroid-sparing therapies are made available. He states that one of the big challenges has been;

“Trying to understand how to objectively measure and quantify steroid-related side effects and how to quantify the beneficial effects of drugs that we are developing in the field of immunology.

Historically, we have not been very successful at quantifying steroid-toxicity, because the toxicities affect so many different organs. Now with the Steritas Glucocorticoid Toxicity Index, we have a consistent and objective way to measure steroid toxicities.”

While Dr Sridharan does point to the need for clinicians and trial investigators to be trained to collect data consistently among sites and investigators, he emphasizes that robust operational implementation of the Steritas GTI within provider platforms is critical so that sponsors can maximize the impact GTI data has with regulators.

“The regulatory agencies have been prescriptive in asking for sponsors to present data demonstrating the reduction in steroid-related side effects in order for them to grant a steroid-sparing claim.”

Dr Sridharan explains that historically steroid-sparing details would get captured in the safety reporting process and were often overlooked as a steroid-related side effect, complicating the ability to prove steroid-sparing benefits.

“The onus now falls on the trial sponsor to demonstrate what they mean by steroid-sparing and how that translates into healthcare benefits such as reduced hospitalizations, and improved quality of life.

You can’t just say that you give steroids to both the active and placebo group and taper the steroid dose down to 5 or 10 mg of prednisone a day and get them to stay there for 2 or 3 months, you need to be able to demonstrate the threshold that you've reached is meaningful. You also need to be able to objectively measure the effects steroids have had on organ systems. Are they worsening diabetes? Causing cataracts? Causing more infections? Or causing more fractures?”

In turn, these data assist in making the health economic case for market adoption.

“If we go to an agency such as a US insurance company, or the UK’s NICE, we need to be able to show objectively that a new treatment can reduce the steroid-related side effects using a measure such as the GTI. On top of that, we also need to show the health economic benefits correlate with the GTI data and be able to deliver a two-pronged approach to demonstrating benefits to the patient and the payer.”