STRIDENTCD · Treatment strategy
Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial
Schulberg JD, et al.
Lancet Gastroenterol Hepatol 2022 · PMID 34890567 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(21)00393-9 (full paper, opens in a new tab)
| Endpoint | Intensive | Standard | Difference |
|---|---|---|---|
| Obstructive symptoms improved, 14-day symptom score down ≥1 point (primary endpoint) | 79% (41/52) | 64% (16/25) | OR 2.10 (95% CI 0.73–6.01); P=0.17 |
| Treatment failure, Lower is better | 10% (5/52) | 28% (7/25) | OR 0.27 (95% CI 0.08–0.97); P=0.045 |
| MRI stricture improvement, MaRIA score down ≥25% | 61% (31/51) | 28% (7/25) | OR 3.99 (95% CI 1.41–11.26); P=0.0091 |
Most strictures improved on adalimumab in either arm: drug therapy is an option for an inflamed stricture.
Source: Schulberg 2022, abstract. Odds ratios are intensive vs standard.
Structured abstract
BackgroundSurgery and endoscopic dilation were the main treatments for Crohn's strictures, and drug therapy was often considered contraindicated, although most strictures have an inflammatory component.
MethodsOpen-label, single-centre randomised controlled trial (Melbourne, Australia), 2:1 allocation; 12 months. 77 patients. Primary endpoint: Improvement (fall of 1 point or more) in the 14-day obstructive symptom score at 12 months.
ResultsPrimary result. 79% (41/52) with intensive therapy vs 64% (16/25) with standard therapy; OR 2.10 (95% CI 0.73–6.01); P=0.17 (not significant).
Take-homeSymptomatic Crohn's strictures with active inflammation often respond to adalimumab; intensifying therapy did not significantly improve symptoms; secondary results on treatment failure and MRI stricture appearance favoured it but are hypothesis-generating.
| Patients | 77 |
|---|---|
| Population | Adults with a de novo or anastomotic small bowel stricture on MRI or ileocolonoscopy, obstructive symptoms (post-prandial pain) and evidence of active inflammation. |
| Comparison | Intensive therapy (adalimumab 160 mg weekly for 4 weeks, then 40 mg every 2 weeks with escalation at 4 and 8 months if inflamed, plus a metabolite-guided thiopurine; n=52) vs standard adalimumab monotherapy (160/80 mg, then 40 mg every 2 weeks; n=25) |
| Drugs | adalimumab, azathioprine, mercaptopurine |
| Classes | Anti-TNF, Thiopurine |
| Published | Schulberg JD, et al. Lancet Gastroenterol Hepatol 2022;7:318–31. |
Key points
- Treatment failure: 10% (5/52) vs 28% (7/25); OR 0.27 (95% CI 0.08–0.97); P=0.045. Stricture surgery was needed by 4 patients in each arm.
- MRI stricture improvement (MaRIA 25% or more): 61% (31/51) vs 28% (7/25); OR 3.99 (1.41–11.26); P=0.0091. Complete resolution on MRI 20% vs 16% (P=0.70).
- CDAI below 150: 69% vs 60% (P=0.42). Serious adverse events 15% vs 16%; no deaths.
- Long-term follow-up (at least 4 years): after the 12-month trial, 16% (12/77) needed endoscopic dilation and 29% (22/77) surgery; surgery was less common in 12-month clinical responders (20% vs 52%; P<0.001) (PMID 40972879).
- A baseline MRI risk score (prestenotic dilation 30 mm or more, stricture longer than 50 mm, wall thickness 10 mm or more) predicted surgery-free survival: OR 2.34 (95% CI 1.32–4.16) (PMID 40972879).
Limitations
- Single centre, open-label and small, with wide confidence intervals.
- Only strictures with active inflammation were included; fibrotic strictures without inflammation were not studied.
- Partly industry funded (AbbVie).
Commentary
STRIDENT challenged the old teaching that a stricture means surgery or dilation. Most patients with a symptomatic inflammatory stricture improved on anti-TNF therapy, and many avoided surgery for years.
How to use it: assess each stricture for inflammation (calprotectin, CRP, intestinal ultrasound or MR enterography). An inflammatory stricture without high-risk features is reasonable to treat medically first, with close monitoring and early surgical review if obstruction persists. Long strictures, marked prestenotic dilation or very thick walls predict surgery and favour an earlier surgical opinion. Ultrasound and MRI both tracked stricture response in a STRIDENT imaging substudy (PMID 40339148).
Journal club
Design
Open-label, single-centre randomised controlled trial (Melbourne, Australia), 2:1 allocation; 12 months. 77 patients.
Primary result. 79% (41/52) with intensive therapy vs 64% (16/25) with standard therapy; OR 2.10 (95% CI 0.73–6.01); P=0.17 (not significant).
Validity and applicability
- Single centre, open-label and small, with wide confidence intervals.
- Only strictures with active inflammation were included; fibrotic strictures without inflammation were not studied.
- Partly industry funded (AbbVie).
Where it sits now
Symptomatic Crohn's strictures with active inflammation often respond to adalimumab; intensifying therapy did not significantly improve symptoms; secondary results on treatment failure and MRI stricture appearance favoured it but are hypothesis-generating.
- PROFILE (2024): In newly diagnosed active Crohn's disease, starting infliximab plus an immunomodulator straight away gives far better 1-year and 5-year outcomes than step-up care.
- STARDUST (2022): With ustekinumab, an endoscopy-driven treat-to-target algorithm did not improve 48-week endoscopic response over clinically driven care; treat-to-target only helps if escalation has something to add.
- CALM (2017): Escalating therapy on biomarkers plus symptoms, rather than symptoms alone, gives more mucosal healing in early Crohn's disease.
- REACT (2015): Early combined immunosuppression did not improve 1-year symptom remission but lowered 2-year surgery, admissions and complications, supporting early effective therapy.
Questions for discussion
- The symptom endpoint missed, but MRI and treatment failure favoured intensive therapy. Which outcome matters most to a patient with a stricture?
- The intensive arm combined higher adalimumab dosing with a thiopurine. Which component do you think drove the effect, and how could you tell?
- How would you choose between medical therapy, balloon dilation and surgery for a short, inflamed ileal stricture?