DOP85 Crohn's Disease Strictures Respond to Drug Treatment and Treat-to-Target Intense Combination Therapy is More Effective than Standard Anti-TNF Therapy. Two year results of the STRIDENT Randomised Controlled Trial.
Schulberg, J.(1,2)*;Hamilton, A.(1,2);Wright, E.K.(1,2);Holt, B.(1,2);Lovett, G.(1,2);Sutherland, T.(2,3);Ross, A.(1);Vogrin, S.(2);Kamm, M.(1,2);
(1)St. Vincent's Hospital Melbourne, Department of Gastroenterology, Melbourne, Australia;(2)University of Melbourne, Department of Medicine, Melbourne, Australia;(3)St. Vincent's Hospital Melbourne, Department of Radiology, Melbourne, Australia;
Background
The randomised STRIDENT (Stricture Definition and Treatment) trial showed that Crohn’s disease symptomatic strictures are responsive to anti-TNF therapy with most patients clinically improved after 12 months treatment with adalimumab +/- thiopurine. Treat to target intensification resulted in greater stricture morphology improvement. We present here 2 year (from study entry) follow up to assess response durability and risk of surgery.
Methods
Patients with symptomatic Crohn’s disease strictures and associated inflammation (elevated faecal calprotectin and CRP) were assessed with imaging (intestinal ultrasound and MRI) and ileo-colonoscopy. The Obstructive Symptom Score (OSS) was used for clinical assessment. Patients were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) followed by 40mg fortnightly plus thiopurine, with adalimumab dose increase at 4 and/or 8 months if evidence of ongoing inflammation, versus standard dose adalimumab monotherapy. The primary endpoint was improved OSS at 12 months. Patient interview was conducted at 24 months, assessing drug treatment, symptoms, need for endoscopic therapy, hospitalisation and surgery.
Results
In the initial 12 months study 52 patients were randomised to the intensive and 25 to the standard treatment arm. 64/77 (83%) patients recorded an outcome at 12 months (13/77 (17%) withdrawn: 8 surgery, 5 other) 74/77 (96.1%) patients were followed up at a mean of 25.3 (IQR 24.4-26.3) months. Of these, 59 (79.7%) remained on adalimumab, 10 (13.5%) had switched to another biologic and 5 (6.7%) had ceased biologic therapy. For patients who were on adalimumab at 12 months the risk of surgery by 24 months was 15%. Of patients on adalimumab 40mg fortnightly at 12 months, 12/48 (25%) had been dose escalated by 24 months. Endoscopic balloon dilatation, hospitalisation or surgery was required in 6 (8.1%), 14 (18.9%) and 13 (17.5%) respectively; rates were not different between the standard and intensive treatment groups (P = 0.982). Median time to intestinal resection was 12.2 (IQR 6.9-18.6) months. Clinical responders at 12 months, compared to non-responders, had a reduced likelihood of surgery at 24 months (9% vs 42%, P=0.003).
Conclusion
Clinical response to adalimumab for structuring Crohn’s disease is durable in a majority of patients, with most patients remaining on adalimumab and avoiding surgery at two years. Rates of surgery were not different between the standard and intensive therapy arms. Clinical response to adalimumab at 12 months is an important predictor of future surgical risk.