Despite decades of widespread use, steroids are facing a growing backlash. Leading researchers and sponsors are aligning on a new imperative: quantify the harm. A flurry of guidance, tools, and regulatory interest now make it clear - steroid-toxicity must be measured, not assumed. And it’s reshaping drug development.

As steroid-sparing therapies advance, measuring the burden of background steroids is no longer optional. According to experts, including Andreas Reiff, MD, and stakeholders across the industry, trials are increasingly expected to answer: Does the new therapy reduce not just disease activity but also steroid harm?

 “Even in a low dose, glucocorticoids can do a lot of harm. The best steroid is no steroid,” says Andreas Reiff, MD.

Validated tools such as the Steritas GTI and the rest of the STOX® Suite provide trial sponsors with the metrics they need to assess the harms associated with steroids. Regulators, payers, and target product profile (TPP) architects are taking notice.

The TPP: the roadmap to success

A TPP is the roadmap that defines what success looks like for a new therapy. It outlines key attributes such as efficacy, safety, dosing, and administration and aligns teams across research, clinical, regulatory, and commercial functions.

Core components typically include:

• Indication and treatment goals  
• Efficacy and safety measures  
• Dosing and administration details  
• Minimum, target, and ideal performance criteria

The TPP evolves with new data, guiding development decisions and helping communicate a therapy’s value to stakeholders.

"If the GTI was included in a Target Product Profile over the course of a clinical development program, it could really help a company capture the benefits of a therapy in reducing steroid dosage and steroid-related toxicity, alongside key elements of efficacy, safety, dosage, and administration," Paul Brunetta, MD.

Integrating steroid-toxicity into the TPP

TPPs that fail to quantify a reduction in steroid-related harms, thanks to steroid-sparing therapies, risk missing a major component of the cost-benefit analysis.

Drug developers are now:

• Including steroid-toxicity endpoints as key secondary outcomes
• Targeting meaningful reductions in GTI scores that exceed the minimally important clinical difference (MCID)
• Designing aggressive taper protocols

This strategic framing ensures that toxicity reduction is not just demonstrated but can be claimed in the label.

"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 that the threshold you've reached is meaningful,” says Sudhakar Sridharan, MD, Vice President in Medical Science & Strategy Division at PPD/ThermoFisher. 

Why it matters

With real-world evidence mounting, from increased costs in asthma to irreversible harm in lupus nephritis, the industry is pivoting. Clinical researchers are no longer asking if to measure steroid-toxicity. They’re asking how soon they can begin.

This marks a turning point in autoimmune trials, one where steroid-toxicity isn't just a concern but a quantifiable outcome that plays a role in the regulatory journey.