A wave of clinical trial results using the STOX® Suite of clinical outcome assessments (COAs) in a range of diseases will soon reach the shore, helping to deliver new therapeutic options for steroid-treated patients. These studies are exploring the efficacy and safety of new steroid-sparing therapies and our understanding of the drivers of steroid-toxicity at the individual patient level. Here, we look at some of the most exciting trials scheduled to report out in the next year or two.
The need to demonstrate a reduction in steroid exposure and toxicity as part of the safety and efficacy profile of new treatments for inflammatory diseases has seen a dramatic increase in the use of the STOX Suite as a secondary outcome measure to support the clinical development of new steroid-sparing treatments.
Sponsored by Novartis, GCAptAIN (NCT04930094) is a phase 3 trial assessing the efficacy and safety of an IL-17A inhibitor (secukinumab) in giant cell arteritis (GCA). The trial has recruited 350 adult patients with GCA at 104 locations worldwide.
Secukinumab (300mg and 150mg) or placebo will be administered subcutaneously in combination with glucocorticoid tapering. The STOX Suite will be pivotal in demonstrating the ability of secukinumab to reduce glucocorticoid toxicity in this debilitating condition that afflicts millions of adults over the age of 50 across the world.
Novartis is sponsoring the REPLENISH trial (NCT05767034), a phase 3 study also investigating the efficacy and safety of secukinumab, this time in polymyalgia rheumatica (PMR) patients experiencing disease relapse. Despite the fact that PMR is a common inflammatory disorder in older adults, treatment remains heavily dependent on long-term steroid use.
This multicenter, double-blind, placebo-controlled trial of 350 patients is likely to report topline results later this year and is using the Steritas GTI as a critical secondary outcome measure to evaluate the long-term burden of steroid exposure.
Zenas BioPharma is leading the INDIGO trial (NCT05662241), a phase 3 study assessing the efficacy and safety of obexelimab in preventing flares of IgG4-related disease (IgG4-RD). This chronic, immune-mediated disorder leads to tissue fibrosis and organ dysfunction. With glucocorticoids remaining the primary treatment, this multicenter, double-blind, placebo-controlled study aims to explore a steroid-sparing alternative.
The trial aims to assess obexelimab’s ability to delay time to the first disease flare requiring rescue therapy. The Steritas GTI is being used as a key secondary outcome measure to quantify steroid-toxicity alongside patient-reported outcomes (PROs) and cumulative glucocorticoid use.
Idiopathic inflammatory myopathies (myositis) constitute a rare group of autoimmune diseases characterized by reduced muscle strength and endurance. Often severe and disabling, myositis can have a profound impact on quality of life. Steroids are the mainstay therapy, with immunomodulators such as azathioprine and methotrexate often added to the mix to reduce steroid dosage and minimize glucocorticoid-associated toxicities. New therapies that target pathways involved in the pathogenesis of myositis are urgently needed to tackle the limited efficacy of this current approach.
The phase 3 ALKIVIA+ trial (NCT05979441) is exploring the long-term safety, efficacy, and tolerability of efgartigimod in 240 newly diagnosed adult patients with active myositis, with the STOX Suite supporting secondary endpoints focused on reduction of steroid-toxicity. This 4-year study aims to deliver the first targeted treatment for myositis.
Despite more than 75 years of steroid use and research into the impact of steroid-associated toxicities on patients undergoing long-term steroid therapy, we still don't understand what determines the tendency to develop steroid-toxicities at an individual level. The following studies, powered by the STOX Suite, may help address this knowledge gap.
An exciting investigator-led trial, supported by Novartis (NCT05479448), is exploring predictors of steroid treatment response in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA).
Glucocorticoids are the first-line treatment for both conditions; treatment dose, duration, and response vary significantly between patients. Rapid tapering of glucocorticoids can reduce steroid-associated toxicity in GCA, but a high relapse rate makes steroid tapering a challenge.
The study explores the association between endogenous glucocorticoid suppression and response to steroid therapy in 30 newly diagnosed GCA and/or PMR patients on prednisone tapering regimens. Glucocorticoid-associated toxicity at 1 year, assessed by the GTI, is a key secondary outcome. Reporting in 2025, the study should provide valuable insights into the drivers of steroid response and toxicity that could enable patient-centric steroid treatment to improve response, minimize toxicity, and enable safer tapering.
Two further studies are using the STOX Suite to explore the predictors of individual response and risk of developing steroid-associated morbidities and the nature and prevalence of glucocorticoid-induced morbidities, respectively. “PRODIGIOUS: PRediction of DIverse Glucocorticoids ToxIcity OUtcomeS" (NCT04664465) in France and “Investigating the Morbidity of Glucocorticoid Use in Patients With Autoimmune Bullous Diseases (AIBDs) (NCT05525065) in Australia are expected to report out in 2025 and 2026.
These studies demonstrate the versatility of the STOX Suite in supporting studies to better understand the basis of steroid-toxicity in diverse conditions.
The STOX Suite supports the development of new therapeutic options for steroid-treated patients across thousands of sites and a wide range of diseases globally. There are many more studies where the use of the STOX Suite enables clinicians to better understand patient responses to therapy and how associated side effects develop within individuals. These studies promise to provide the foundation to support successful steroid tapering and improve patient outcomes and quality of life.