Treat-to-target in Crohn’s and UC: Optimizing therapy, de-escalating thiopurines, and defining steroid thresholds
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We should be spending more time trying to find the mild patients with Crohn's that can be monitored and treated with lifestyle changes and spend less time making patients with Crohn's disease 'earn' a highly effective treatment. Delays equal complications and surgery.
—Raymond K. Cross, Jr, MD, MS, AGAF, FACG
IBD management has shifted from symptom control to objective disease control. Treat-to-target strategies now guide therapy, with clear endpoints and defined timelines for action.
Targets are defined and measurable
The STRIDE-II consensus from the International Organization for the Study of IBD defines clinical remission and normalization of biomarkers as short-term goals. Endoscopic healing is the primary long-term target. []
For clarity, three disease activity measures are commonly used in IBD: symptom-based scores such as PRO2 (patient reported outcome 2), Harvey-Bradshaw Index, and partial Mayo score; objective markers such as C-reactive protein (CRP) and fecal calprotectin; and endoscopic indices such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD), which grades ulcer size, ulcerated surface, affected surface, and strictures across bowel segments to assess mucosal disease severity. []
Short-term targets (early response phase)
Clinical response
Crohn’s disease (CD): ≥50% reduction in PRO2 (stool frequency and abdominal pain)
Ulcerative colitis (UC): ≥50% reduction in PRO2 (stool frequency and rectal bleeding)
Symptom improvement expected within weeks depending on therapy (2-4 weeks for biologics)
Intermediate targets (weeks to months)
Clinical remission
CD: PRO2 normalization or HBI <5
UC: no rectal bleeding, normal stool frequency, or partial Mayo <3
Biomarker normalization
Biomarkers are utilized for treatment adjustment even without symptoms
CRP: within normal range
Fecal calprotectin: target <100–250 µg/g
Long-term targets (disease modification phase)
Endoscopic healing
Associated with reduced flares, hospitalizations, and surgery risk
Restoration of quality of life and absence of disability are included as formal targets
CD: absence of ulceration or SES-CD ≤2–3
UC: Mayo endoscopic score 0 or 1
This framework changes how the response is assessed. Symptoms alone are insufficient. Persistent inflammation, even in asymptomatic patients, predicts relapse and long-term complications.
Tight control improves outcomes
Current guidelines from the AGA and ACG specify the following as standard options for moderate-to-severe IBD: anti-TNF agents; JAK inhibitors; vedolizumab (anti-integrin therapy); ustekinumab (Stelara), which blocks both IL-12 and IL-23; and selective IL-23 inhibitors like risankizumab (Skyrizi), mirikizumab (Omvoh), and guselkumab (Tremfya). [] []
The CALM trial provides prospective evidence for biomarker-driven care. [] Patients managed with tight control with immunosuppressants and biologicals, using both symptoms and biomarkers as measures, achieved higher rates of mucosal healing than those managed by symptoms alone. The primary endpoint was reached in 46% of the tight-control group compared with 30% in the clinical-management group.
Board-certified gastroenterologist Raymond K. Cross, Jr., MD, MS, AGAF, FACG, Medical Director of The Center for Inflammatory Bowel and Colorectal Diseases at Mercy in Baltimore, says, “Most patients with Crohn's disease have moderate to severe disease and should be on a biologic or JAK inhibitor.”
He further adds, “JAK inhibitors and IL-23 inhibitors are both highly effective treatments for patients with IBD. In both ulcerative colitis and Crohn's disease, I tend to use the IL-23 inhibitors in less-sick outpatients, as the onset of action of these agents is slower than JAK inhibitors. I use JAK inhibitors in patients with both Crohn's and ulcerative colitis that have more severe symptoms, typically after another advanced therapy has been ineffective.”
Thiopurine de-escalation after remission
Combination therapy with anti-TNF agents and thiopurines remains effective during induction. The SONIC trial showed corticosteroid-free clinical remission at week 26 in 56.8% of patients treated with infliximab plus azathioprine, compared with 44.4% with infliximab alone and 30.0% with azathioprine alone. []
The role of thiopurines after remission is less clear. Thiopurines improve outcomes in combination therapy but carry long-term risks, including lymphoma, as shown in large IBD cohorts. []
In patients with sustained remission on biologic therapy, withdrawal of thiopurines has been studied. In the SPARE randomized trial, withdrawal of azathioprine in patients with Crohn’s disease in remission on infliximab-based combination therapy did not increase relapse over 2 years. []
However, for UC, evidence is more limited, with studies showing higher relapse rates after thiopurine withdrawal, particularly outside combination therapy. []
Steroid thresholds define treatment failure
Corticosteroids remain widely used but should be limited to induction. Ongoing need for steroids reflects inadequate disease control.
The ECCO consensus defines steroid dependence as inability to taper prednisolone below 10 mg within 3 months, or relapse within 3 months of discontinuation. [][]
Steroids have no role in maintenance therapy. Continued use exposes patients to infection, metabolic complications, and thromboembolic risk. []
Repeated steroid courses should trigger escalation to advanced therapy rather than continuation of the same approach.
Dr. Cross elaborates, “We should be spending more time trying to find the mild patients with Crohn's that can be monitored and treated with lifestyle changes and spend less time making patients with Crohn's disease 'earn' a highly effective treatment. Delays equal complications and surgery.”
He further adds, “For UC, about half of patients do fine on our 'entry level' treatments, aminosalicylates. However, when these fail or a patient receives steroids, we should move on to other treatments that are more effective to minimize steroid exposure and to improve quality of life.”