For over 75 years, steroids have been a key treatment for autoimmune and inflammatory diseases. However, while they offer rapid symptom relief, their long-term use is associated with serious and often under-recognized toxicities. Despite this, steroids are still widely prescribed, creating what many now describe as a hidden epidemic of steroid-induced harm.

Recognizing the urgent need for change, Steritas launched the public health initiative 'The Great Taper™' to raise awareness of steroid toxicity and promote alternative treatment strategies. Central to this effort was the development of the Glucocorticoid Toxicity Index (GTI) — the first validated tool for objectively measuring steroid-induced harm.

Drug Discovery News spoke with John Stone, rheumatologist at Harvard Medical School and the Massachusetts General Hospital, and Chair of the Scientific Advisory Board at Steritas, to discuss the origins and impact of the GTI. Stone led the international consortium that developed the index and continues to guide its clinical implementation and evolution.

Why are steroids the first line of treatment for autoimmune diseases?

Glucocorticoids provide a fast-acting treatment by suppressing physiological pathways associated with inflammatory and immune responses. By inhibiting the production of cytokines, prostaglandins, and other inflammatory mediators, glucocorticoids reduce the symptoms caused by conditions such as asthma, rheumatoid arthritis, and lupus.

The first synthetic glucocorticoid, cortisone, was developed and administered for the treatment of rheumatoid arthritis in 1948. However, 23 days later, the first toxicities were reported. The next day, the first steroid taper began, and the need to develop steroid-sparing alternatives has continued ever since.

What are some of the side effects associated with long-term steroid use?

Over one percent of the world’s adult population takes steroids long-term. It is well-known that patients should receive the lowest possible dose to achieve the desired therapeutic effects, but even minimal doses are accompanied by severe side effects, both short- and long-term.

Steroids impact many of the body’s major organ systems, therefore, side effects can affect most organs. Even short-term use can cause high blood pressure, osteoporosis, muscle weakness, acne, diabetes, and mental health impacts such as anxiety.

Why has progress in reducing and replacing steroid treatment for autoimmune diseases been relatively slow, and what are the main barriers to developing effective alternatives?

Steroids provide significant short-term benefits, instantly reducing inflammation-associated symptoms. Additionally, they are cheap and easy to prescribe; they have been the standard of care for many conditions for over 75 years. In contrast, many novel steroid-sparing therapeutics that demonstrate similar anti-inflammatory and immune-suppressive effects can be more expensive to administer and not accessible to all patients.

Convincing payers to take the long view is a practical challenge. Helping health systems recognize that steroid-sparing therapies are worth the upfront cost requires time and data. Without an evidence-based tool, it is difficult to quantify the positive impact that steroid tapering and alternative therapeutics can provide.

Can you share insights from your work with the international group focused on glucocorticoid toxicity? What promising strategies or therapies are emerging?

For clinicians, the need to quantify and monitor steroid toxicity is obvious, but until recently there was no standardized way to measure it. That’s what drove an international collaboration of global experts to develop the GTI, the first validated tool for objectively assessing steroid toxicity in clinical settings.

We identified inclusion criteria, selected health domains that respond to treatment, weighted each domain, and validated the tool through clinical trials. By combining the cumulative worsening score (CWS) and aggregate improvement score (AIS), the GTI uses BMI, blood pressure, glucose metabolism, and neuropsychiatric effects to assess change in steroid toxicity for an evidence-based approach to the treatment of autoimmune diseases.

The GTI enables a data-driven approach to managing autoimmune diseases, supporting both clinical decision making and the evaluation of emerging steroid-sparing therapies. This foundation led to the creation of Steritas, a company focused on reshaping steroid-prescribing habits and enabling safer, more personalized treatment strategies.

What recent advancements are enabling more precise steroid tapering?

The introduction of the GTI provides real-world data that demonstrates the benefits of early intervention. The GTI is the core asset in a growing collection of clinical outcome assessments, known as the STOX® Suite. Designed to measure steroid toxicity, STOX tools are used across clinical and health economics outcomes research, routine practice, and direct-to-patient applications. These instruments are being used in over 30 disease indications, across 3,000 sites in 80 countries.

In a longitudinal study published in the Journal of Allergy and Clinical Immunology, the GTI demonstrated that patients with severe asthma can develop long-term steroid toxicities that may not improve even with a reduction in oral glucocorticoid dosage (1). The key takeaway is that changes in GTI Scores at one year reliably predicted outcomes at three years, reinforcing the importance of early and proactive steroid tapering to minimize long-term toxicity.

The PONENTE trial explored the use of benralizumab, a monoclonal antibody, in patients with severe eosinophilic asthma (2). This showed that a personalized oral glucocorticoid tapering regimen, when combined with a steroid-sparing therapy, can significantly reduce or even eliminate steroid use. The findings support the development of individualized steroid reduction protocols to improve patient outcomes and minimize long-term toxicity.

How is the drug discovery field addressing the need for effective steroid-sparing therapies, and what recent breakthroughs are showing promise in preclinical or clinical settings?

We are at an exciting point in countering the hidden epidemic of steroid toxicity. Growing research is shining a light on the real-world impact on patients and driving momentum toward improved standards of care. This includes wider adoption of tools like the GTI, greater patient engagement, and a surge in interest from the drug discovery community in developing steroid-sparing therapies that prioritize safety without compromising efficacy.

One disease area with significant progress in developing steroid-toxicity sparing therapeutics is asthma. Despite six approved monoclonal antibodies for treatment, 60 percent of patients with severe asthma remain on chronic systemic steroids. Glucocorticoids are still overused, and many patients are unaware that effective alternatives exist. A major breakthrough came with results published in The Lancet Respiratory Medicine, showing that benralizumab could be used routinely to treat up to two million asthma exacerbations annually in the UK, dramatically reducing healthcare burdens (3). This marks the first major change in asthma treatment in five decades, offering new hope for reducing reliance on long-term steroid use.

What emerging drug classes or therapeutic targets are being explored as alternatives to steroids in the management of autoimmune diseases?

A notable example is the recent progress in treating immunoglobulin G subclass 4-related disease (IgG4-RD), a chronic autoimmune inflammatory condition that can affect nearly any organ system. Until now, glucocorticoids have been the mainstay of treatment despite their well-known toxicity risks.

Earlier this year, inebilizumab became the first approved therapy specifically for IgG4-RD. In the MITIGATE trial, inebilizumab significantly reduced the risk of disease flares and increased the proportion of patients achieving flare-free complete remission at one year (4). Remarkably, 90 percent of patients receiving inebilizumab were able to discontinue steroids entirely following the required taper, highlighting its potential as a true steroid-sparing alternative.

How is the increased awareness of steroid toxicity helping to improve patient outcomes?

The increased recognition of steroid toxicity both within the medical field and general population is a crucial first step toward safer, more effective treatment. But awareness alone isn’t enough. To truly improve outcomes, we must empower researchers to advance steroid-sparing therapeutics and support patients in navigating the challenges of long-term steroid use. That’s the mission behind public health efforts like The Great Taper.

Pairing increased awareness with education and accessibility to the correct tools and resources is essential. Our goal is to deliver end-to-end solutions to address the steroid-toxicity epidemic — working with academia, industry, and clinicians to drive progress from research to real-world care.

One major barrier has been the lack of credible, patient-friendly information on steroid side effects and alternatives. To close this gap, we launched Steroids and Me (Sam), a digital platform that helps patients manage their steroid journey. With resources like educational videos, a side effect tracker, and tools for shared decision making, Sam empowers patients to take an active role in their care. Already, over 5,000 patients have engaged with the platform. By partnering with advocacy groups across diseases from asthma to vasculitis, we’re demonstrating how patient-centered innovation can directly improve outcomes.

References:

1. McDowell, P. J., Busby, J., Stone, J. H., Butler, C. A. & Heaney, L. G. Longitudinal Assessment of Glucocorticoid Toxicity Reduction in Patients With Severe Asthma Treated With Biologic Therapies. The Journal of Allergy and Clinical Immunology: In Practice 13, 298-307.e10 (2025).
2. Menzies-Gow, A. et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. The Lancet Respiratory Medicine 10, 47–58 (2022).
3. Lipworth, B., Misirovs, R. & Chan, R. Adrenal insufficiency in patients taking benralizumab as corticosteroid sparing therapy. The Lancet Respiratory Medicine 10, e7 (2022).
4. Stone, J. H. et al. Inebilizumab for Treatment of IgG4-Related Disease. New England Journal of Medicine 392, 1168–1177 (2025).