Navigating Steroid-Refractory irAEs: What Pharmacists Need to Know

Immune checkpoint inhibitors have reshaped cancer care, but their growing use has brought a corresponding rise in immune-related adverse events—and a small, especially challenging subset of patients who fail to respond to steroids. For many oncology pharmacists, these cases are rare enough to feel unfamiliar, yet urgent enough to require swift and decisive action. In this interview at the Hematology/Oncology Pharmacy Association 2026 Annual Conference, Emma Jones, PharmD, BCOP, shares practical guidance on identifying steroid refractoriness, selecting second-line immunosuppressants, and using consensus guidelines to navigate a still-evolving evidence base.

Q: Immune-related adverse events (irAEs) are increasingly common as immunotherapy use expands, but steroid-refractory cases represent a particularly challenging subset. How would you frame the scope of this problem for pharmacists who may only occasionally encounter these patients?
Emma Jones, PharmD, BCOP: I think that with the ubiquitous use of immunotherapy, many oncology pharmacists are pretty used to dealing with these irAEs, but these steroid-refractory cases remain limited and rare, where I’d say the average clinical pharmacist has probably only seen a handful of these per year. I think the problem is very real—feeling uncomfortable in the unknown here—but pharmacists can definitely play a big role in the management of these cases with early recognition and timely intervention, and we’re the main ones recommending escalation of care. So I think that as long as pharmacists know the key concepts of these cases, they’ll be well prepared when they come into their clinical practice.

Q: When we talk about the “big 4”—colitis, pneumonitis, hepatitis, and myocarditis—are there meaningful differences in how quickly pharmacists should expect steroid refractoriness to declare itself, or is the timeline fairly consistent across these toxicities?
Jones: I think the timeline and the thresholds to define steroid refractoriness have been a bit of a challenge when it comes to diagnosing and managing these patients, because it’s been inconsistent across the literature and even in the way providers speak about these cases. Luckily, in 2023 the Society for Immunotherapy of Cancer created more standardized consensus definitions, and it’s going to depend on the organ system involved. It will depend on whether it’s a life-threatening or non–life-threatening irAE. We kind of lump them into those 2 buckets, where I would consider colitis, pneumonitis, and myocarditis to be life-threatening irAEs, and we would consider them to be steroid-refractory in roughly 1 to 3 days. Hepatitis is not as imminently life-threatening, so we allow a little more time to see if those steroids will take effect and wouldn’t consider it to be refractory until even 14 days of steroid therapy. So it will vary. I will say that these definitions are a bit fluid. We definitely depend on those consensus definitions, but you’ll still see variations in the literature.

Q: Walk us through what treatment escalation looks like in practice. At what point should a pharmacist be raising the flag that a patient isn’t responding adequately to steroids, and what agents are typically next in line?
Jones: I would say the timeline to define refractoriness is going to depend on the organ involved, like I mentioned, and the escalation and choice of the agent can also depend on that organ. For example, we use infliximab (Remicade; Janssen) in patients with colitis, but we don’t want to use that in hepatitis. The agents that we use span a large spectrum. We’ve got nonselective agents—your normal, run-of-the-mill immunosuppression, things like mycophenolate (CellCept; Genentech) or IVIG or tacrolimus (Prograf; Astellas Pharma). Then we have newer, more targeted agents as well, things like infliximab or vedolizumab (Entyvio; Takeda) that we can use. I think that’s a key role of the pharmacist in the management of these steroid-refractory patients: making that intentional selection of whatever is best for the patient in that case.

Q: The literature on secondary immunosuppressants for steroid-refractory irAEs is still limited. How do you counsel pharmacists on making evidence-informed decisions in a space where the data isn’t always strong or consistent?
Jones: I think that’s a great question, because this is one of those areas where we have to lean into the grays of medicine. We might not have a black-and-white answer for every one of these cases because the literature is so limited, and it’s often based on case reports and case studies. I’d say, first and foremost, pharmacists should rely on the consensus guidelines we have. This is where experts can collate and synthesize all of the data into one place. They are amazing, but they vary as well—NCCN might look different than ASCO—so just know that. You can compare and contrast those guidelines as a great resource and first step, but also dive into the primary literature behind specific irAE cases you may encounter. If you’re really interested, you could even look into the naturally occurring autoimmune diseases that drive many of those recommendations. Because the data is so limited, I’d say prioritize patient safety, use your clinical judgment, and collaborate on these complex cases when you can.