Glucocorticoids have been the cornerstone of treatment of inflammatory diseases for over seven decades. Their ability to rapidly reduce inflammation in a broad range of diseases in the short term must be balanced against the dangers associated with their long term use.  

Despite the dozens of known toxicities they cause, glucocorticoids are still the benchmark against which all new therapies are measured. It’s therefore important that clinical trials are able to demonstrate that these therapies can effectively reduce glucocorticoid-toxicity.

The Glucocorticoid Toxicity Index (GTI) is the first validated clinical outcome assessment (COA) that measures glucocorticoid toxicity directly.  The GTI and its siblings (pGTI and GTI-MD) provide a powerful advantage for cost-effective product design and evidence-gathering at multiple points in the development cycle, including:

• Target Product Profile (TPP) to specify a product that will be safe, effective and commercially viable
• Patient stratification for clinical trial recruitment efforts
• Critical endpoint in clinical trials to demonstrate drug candidate safety, efficacy and performance relative to alternative treatments
• Risk prediction modeling and treatment monitoring to identify at-risk patients who may benefit from earlier initiation of glucocorticoid-sparing therapies

Incorporating the GTI as an essential trial endpoint can provide a competitive advantage to your drug discovery partners and allow you to differentiate yourself from competitors.

ADVOCATE was a phase 3 trial comparing oral avacopan with oral prednisone in ANCA-associated vasculitis (AAV).[1] The primary endpoints were clinical remission at week 26 and sustained remission at 52 weeks. ADVOCATE was the first trial to incorporate glucocorticoid-induced toxic effects as a trial endpoint, using the GTI as the most important secondary endpoint for efficacy.

The trial demonstrated noninferiority of avacopan at 26 weeks and superiority at 52 weeks. The GTI measured glucocorticoid-toxicity results using the GTI cumulative worsening score (CWS) and aggregate improvement score (AIS) at 26 weeks, and showed a reduction in toxicity for the avacopan group as follows:

In response to substantial investment in research and digitization of its COAs, Steritas has seen a surge in licensing and deployment of the STOX Suite. This reflects the growing recognition of the importance of measuring and monitoring steroid-toxicity in pharmaceutical research and clinical practice respectively.

The Steritas STOX Suite (GTI, GTI-MD, and pGTI) has been used in over 75+ clinical trials, in 1100 sites across 80 countries, underlining the growing impact that quantitative steroid-toxicity assessment is having on clinical development in inflammatory diseases.  

Steritas is keen to support studies that align with its goal of reducing the impact of steroid treatment on patients; 90% of applications to date have been successful in accessing GTI instruments for their studies.