A new generation of biologic therapies targeting interleukin-23 is rewriting the treatment landscape for Crohn’s disease, with recent clinical trials showing remission rates approaching 60 percent at one year. Guselkumab, marketed as Tremfya, achieved 59 percent clinical remission at week 48 in the GRAVITI study, compared to just 17 percent with placebo. The FDA approved guselkumab for moderate-to-severe Crohn’s disease on March 20, 2025, making it the first IL-23 inhibitor to offer both subcutaneous and intravenous induction options. For the millions of people living with Crohn’s — and for families already navigating the complexities of chronic disease management alongside conditions like dementia — these numbers represent something concrete: the possibility of sustained relief from a disease that has long resisted easy answers. Guselkumab is not alone in this class.
Risankizumab (Skyrizi) demonstrated 52 percent clinical remission at one year in its FORTIFY Phase 3 maintenance trial, and mirikizumab (Omvoh) reached 53 percent remission at one year in the VIVID-1 study. In head-to-head comparison, risankizumab achieved 59 percent remission versus 40 percent for the older biologic ustekinumab, underscoring a meaningful generational shift in efficacy. These are not marginal improvements. They represent a real change in what patients and gastroenterologists can expect from treatment. This article examines the clinical evidence behind IL-23 inhibitors for Crohn’s disease, compares the leading drugs in the class, explores long-term durability data, addresses safety considerations, and discusses what these advances may mean for patients juggling multiple chronic conditions, including neurodegenerative disease.
Table of Contents
- How Do IL-23 Inhibitors Achieve Nearly 60 Percent Remission in Crohn’s Disease?
- Comparing the Three IL-23 Inhibitors — Where the Differences Matter
- Long-Term Durability — Do These Remission Rates Hold Beyond Year One?
- Safety Profile — What Patients and Caregivers Need to Know
- The Gut-Brain Connection — Why Crohn’s Treatment Matters for Brain Health
- Navigating Treatment Decisions in Complex Patients
- What Comes Next for IL-23 Inhibitors and Crohn’s Disease
- Conclusion
- Frequently Asked Questions
How Do IL-23 Inhibitors Achieve Nearly 60 Percent Remission in Crohn’s Disease?
IL-23 is a cytokine — a signaling protein — that plays a central role in driving the inflammatory cascade responsible for the intestinal damage seen in Crohn’s disease. Unlike older biologics that target broader immune pathways, IL-23 p19 inhibitors block this specific protein with precision, reducing inflammation while leaving more of the immune system’s general surveillance intact. A pooled meta-analysis of IL-23 p19 inhibitors found that clinical remission during induction averaged 42.1 percent versus 20.4 percent with placebo across studies, with maintenance phases pushing those numbers considerably higher. The GRAVITI trial for guselkumab illustrates this trajectory clearly. Patients receiving 100 mg subcutaneously every eight weeks reached 59 percent clinical remission at week 48, with an endoscopic response rate of 39 percent compared to 5 percent on placebo.
Endoscopic response is particularly significant because it measures actual healing of the intestinal lining, not just symptom relief. In Crohn’s disease, the gap between feeling better and being better has historically been wide. IL-23 inhibitors appear to narrow it. What separates these drugs from their predecessors is consistency. Earlier biologics like infliximab and adalimumab often showed strong initial response rates that declined over time as patients developed antibodies against the drugs. The IL-23 class has so far demonstrated more durable efficacy, though long-term real-world data beyond clinical trials is still accumulating.
Comparing the Three IL-23 Inhibitors — Where the Differences Matter
Guselkumab, risankizumab, and mirikizumab all target the p19 subunit of IL-23, but their clinical profiles are not identical. Guselkumab’s 59 percent remission rate at one year in GRAVITI edges ahead of risankizumab’s 52 percent in FORTIFY and mirikizumab’s 53 percent in VIVID-1, though cross-trial comparisons carry inherent limitations. Patient populations, disease severity, prior treatment history, and study design all differ, making direct head-to-head conclusions difficult without dedicated comparative trials. That said, one head-to-head study does exist. Risankizumab achieved 59 percent remission compared to 40 percent for ustekinumab, an IL-12/23 inhibitor.
This is notable because ustekinumab (Stelara) has been a mainstay of Crohn’s treatment for years, and many patients currently on it may now have a demonstrably more effective option in the same biologic neighborhood. However, switching biologics is never a casual decision. Patients who are stable on ustekinumab and managing well may not benefit from the disruption of a transition, particularly if they have comorbidities — such as cognitive impairment or dementia — that make frequent medical appointments and monitoring more burdensome. The March 2026 AFFIRM Phase 3 results added another dimension: risankizumab achieved 55 percent clinical remission at week 12 using subcutaneous-only induction, and among maintenance responders, 67 percent reached clinical remission at week 24. Crucially, 65 percent of the AFFIRM study population was treatment-refractory, meaning these were patients for whom other therapies had already failed. That context matters enormously when interpreting the numbers.
Long-Term Durability — Do These Remission Rates Hold Beyond Year One?
One of the most persistent frustrations in Crohn’s disease treatment has been the tendency of biologic therapies to lose effectiveness over time, a phenomenon clinicians call secondary loss of response. The early durability data for IL-23 inhibitors is, cautiously, encouraging. Guselkumab maintained over 85 percent clinical remission at 96 weeks across both the GRAVITI and GALAXI studies. While that figure represents the subset of patients who were already in remission at year one rather than the full intent-to-treat population, it suggests that for patients who respond, the response tends to last. Mirikizumab offers a particularly interesting long-term story. In the VIVID-2 extension study, 60.8 percent of patients who were not in remission at year one went on to achieve remission during year two.
Among those who were in remission at the one-year mark, 92.9 percent maintained it into year two. Eli Lilly further reported steroid-free remission maintained for three years, announced in February 2026. For patients who have cycled through multiple biologics with diminishing returns, the idea that a drug might actually become more effective with continued use — rather than less — is a meaningful departure from the historical pattern. These durability findings carry particular weight for older patients and those with concurrent neurodegenerative conditions. Managing Crohn’s flares alongside dementia care is exhausting for both patients and caregivers. A therapy that maintains remission for years rather than months reduces the burden of hospitalizations, steroid courses, and the cognitive toll of chronic pain and malnutrition that can worsen neurological decline.
Safety Profile — What Patients and Caregivers Need to Know
The safety data for IL-23 inhibitors as a class has been reassuring relative to other biologic categories. A meta-analysis published in Frontiers in Pharmacology found that IL-23 p19 inhibition was associated with a decreased risk of serious adverse events compared to placebo, based on high-certainty evidence. This is an unusual finding for immunosuppressive therapies, where the trade-off between efficacy and infection risk typically tilts in one direction or the other. That said, decreased risk relative to placebo in a controlled trial does not mean zero risk in practice. Patients on any biologic that modulates the immune system face elevated susceptibility to infections, particularly upper respiratory infections, and require monitoring for tuberculosis reactivation.
For patients with dementia or significant cognitive decline, this monitoring can be complicated by their inability to reliably report new symptoms. A urinary tract infection or pneumonia that a cognitively intact patient would flag immediately might go unnoticed in someone with advanced Alzheimer’s until it becomes serious. The comparison with older Crohn’s therapies is worth noting. TNF-alpha inhibitors like infliximab carry well-documented risks of serious infections and lymphoma with long-term use. Corticosteroids, still commonly used for flare management, cause bone density loss, glucose dysregulation, and cognitive side effects — the last of which is particularly concerning in patients already experiencing neurodegeneration. IL-23 inhibitors appear to occupy a more favorable position on the risk-benefit spectrum, though post-marketing surveillance over the coming years will be critical.
The Gut-Brain Connection — Why Crohn’s Treatment Matters for Brain Health
The relevance of Crohn’s disease treatment to a brain health audience extends beyond the practical overlap of caring for someone with multiple chronic conditions. A growing body of research has documented bidirectional communication between the gut and the brain through what is commonly called the gut-brain axis. Chronic intestinal inflammation alters the gut microbiome, increases intestinal permeability, and elevates systemic inflammatory markers — all of which have been linked to accelerated cognitive decline and increased risk of neurodegenerative disease. Uncontrolled Crohn’s disease can contribute to malnutrition, particularly deficiencies in B12, folate, and iron, all of which are implicated in cognitive function.
Patients experiencing frequent flares may also face chronic sleep disruption and psychological distress, both independent risk factors for dementia progression. By achieving and sustaining remission, IL-23 inhibitors may indirectly support brain health by reducing the systemic inflammatory burden and improving nutritional status, though no clinical trials have directly measured cognitive outcomes in Crohn’s patients on these therapies. It is important not to overstate this connection. No one should interpret Crohn’s remission data as a dementia treatment. But for caregivers managing both conditions in a loved one, or for individuals in early-stage cognitive decline who also carry a Crohn’s diagnosis, understanding that effective gut disease management may have downstream neurological benefits is clinically relevant information worth discussing with a care team.
Navigating Treatment Decisions in Complex Patients
For patients with both Crohn’s disease and cognitive impairment, treatment decisions often involve caregivers, gastroenterologists, neurologists, and primary care physicians who may not be communicating as tightly as the situation demands. The subcutaneous self-injection regimen common to IL-23 inhibitors — typically every four to eight weeks during maintenance — may be manageable for patients with mild cognitive impairment but becomes impractical as dementia advances.
Guselkumab’s availability in both IV and subcutaneous formulations offers some flexibility, as IV infusions can be administered in clinical settings where adherence is guaranteed. Caregivers should ask explicitly about injection training, home health nursing support, and whether the prescribing gastroenterologist’s office coordinates with any existing neurology or memory care providers. The practical logistics of biologic therapy are often as consequential as the drug’s efficacy data, and they are rarely discussed in the same conversation.
What Comes Next for IL-23 Inhibitors and Crohn’s Disease
The IL-23 inhibitor class is still maturing. With three FDA-approved options now available and long-term extension studies continuing to report, the next major milestones will be real-world effectiveness data, head-to-head trials comparing the three drugs directly, and investigation into combination strategies pairing IL-23 blockade with other targeted therapies. The AFFIRM study’s demonstration that subcutaneous-only induction can work effectively may also simplify treatment protocols, removing the need for initial IV infusions that require clinic visits.
Broader questions remain about whether earlier intervention with IL-23 inhibitors — before patients have failed multiple other biologics — might produce even higher remission rates. The treatment-refractory populations studied in many of these trials represent the hardest cases. If these drugs can achieve 55 to 60 percent remission in patients who have already exhausted other options, their ceiling in biologic-naive patients may be higher still. For patients and families dealing with the intersection of inflammatory bowel disease and neurodegenerative illness, these developments offer a reason to stay engaged with evolving treatment options rather than accepting the status quo.
Conclusion
IL-23 inhibitors have established themselves as the most effective biologic class yet for moderate-to-severe Crohn’s disease. Guselkumab’s 59 percent remission at one year, risankizumab’s strong performance in treatment-refractory populations, and mirikizumab’s remarkable year-two gains and three-year steroid-free remission data collectively represent a genuine advance. The class-wide safety profile — with decreased serious adverse events compared to placebo — makes these drugs particularly appealing for complex patients, including those with concurrent neurological conditions where additional medical instability carries outsized consequences.
For caregivers and patients navigating both Crohn’s disease and brain health concerns, the practical takeaway is straightforward: discuss IL-23 inhibitors with your gastroenterologist if current therapy is not achieving sustained remission, coordinate care across specialties, and pay attention to the logistical demands of biologic therapy as cognitive status evolves. The science is moving in the right direction. The challenge, as always, is translating clinical trial success into individual patient benefit.
Frequently Asked Questions
What is an IL-23 inhibitor and how is it different from older Crohn’s treatments?
IL-23 inhibitors target a specific inflammatory protein called interleukin-23, which drives intestinal inflammation in Crohn’s disease. Unlike older biologics such as TNF-alpha inhibitors (infliximab, adalimumab) that block a broader part of the immune response, IL-23 p19 inhibitors are more targeted. This precision appears to contribute to both better efficacy — pooled remission rates of 42.1 percent versus 20.4 percent with placebo during induction — and a more favorable safety profile.
Which IL-23 inhibitor has the highest remission rate for Crohn’s disease?
The figures are close and come from different trials with different patient populations. Guselkumab achieved 59 percent clinical remission at week 48 in the GRAVITI study. Risankizumab reached 59 percent in a head-to-head trial against ustekinumab, and 67 percent among maintenance responders in the AFFIRM study. Mirikizumab showed 53 percent at one year in VIVID-1, but 60.8 percent of non-responders gained remission in the second year. Direct head-to-head comparisons between all three drugs have not been published.
Are IL-23 inhibitors safe for elderly patients or those with dementia?
Clinical trial data shows IL-23 inhibitors are associated with decreased risk of serious adverse events compared to placebo, which is encouraging. However, elderly patients and those with cognitive impairment require additional monitoring since they may not reliably report symptoms of infection or other complications. No specific safety data exists for IL-23 inhibitors in dementia populations, so treatment decisions should involve coordination between gastroenterology and neurology care teams.
How long do IL-23 inhibitors maintain remission?
Early durability data is promising. Guselkumab maintained over 85 percent remission at 96 weeks among year-one responders. Mirikizumab showed 92.9 percent maintenance of remission from year one through year two, with steroid-free remission reported out to three years. These are relatively new drugs, so data beyond three years is limited.
Can treating Crohn’s disease with IL-23 inhibitors benefit brain health?
Chronic gut inflammation is linked to systemic inflammation, malnutrition, and microbiome disruption — all factors associated with cognitive decline. Achieving sustained Crohn’s remission may reduce these risks indirectly. However, no clinical trials have specifically measured cognitive outcomes in Crohn’s patients treated with IL-23 inhibitors, so any brain health benefits remain theoretical at this point.
