Introduction
Transmural healing is a promising target in Crohns’ disease (CD) that is associated with more favorable outcomes than endoscopic remission, especially lower risk of bowel damage progression. C-score has been recently developed and validated to assess transmural healing in patients with CD. However, the best time to assess transmural healing remains to be determined.
Aims & Methods
We aimed to evaluate the kinetics of transmural healing in patients with CD treated with anti-TNF therapy.
From a prospective database of patients with CD performing MRI for luminal CD, we analyzed the kinetics of transmural healing among CD patients older than 18 years-old receiving anti-TNF therapy, with objective sign of inflammation on morphological evaluation (cross-sectional imaging) before starting the treatment, who underwent at least one MRI examination to assess therapeutic efficacy within 12 months. Patients treated with anti-TNF agents for treat isolated perianal lesions were excluded.
We used a statistical model based on imputation according the last observation carry forward and clinical relevance. Transmural healing was then assessed every month during the first year. For segmental analysis, we used the same division into segments than recommended for Lemann Index calculation. Transmural healing was defined as C-score < 0.5 in each segment. C-score was calculated as previously published (0.2 x (bowel thickness in mm – 3) + 2 if ulcer + 1.5 if enlarged lymph nodes).
Results
Overall, 123 patients were included. Among them, 90 were female (73.1%), 48 (39.9%) were current smokers and 53 (43.0%) had prior intestinal resection. The median CD duration at baseline was 7.6 years [1.4-15.2]. At baseline, 41 patients (33.3%) were anti-TNF-naïve. At baseline, 67 patients (55.3%), 53 patients (43.8%) and 1 patient (0.8%) were treated with infliximab, adalimumab and golimumab, respectively with concomitant immunosuppressant in 94 patients (79.0%).
At baseline, 220 segments were considered as active (C-score > 0.5) including 100 in the terminal ileum and 120 in the colon/rectum.
According per-segment analysis (N=220), the rate of transmural healing was 6.4% at M1, 6.4% at M2, 10.0% at M3, 10.1% at M4, 14.6% at M5, 18.0% at M6, 23.2% at M7, 24.5% at M8, 26.0% at M9, 26.8% at M10, 29.1% at M11 and 30.4% at M12.
Among terminal ileum segments (n=100), the rate of transmural healing was 2.0% at M1, 2.0% at M2, 5.0% at M3, 5.0% at M4, 9.0% at M5, 12.9% at M6, 16.0% at M7, 17.0% at M8, 18.0% at M9, 19.0% at M10, 20.0% at M11 and 20.0% at M12.
Among colorectal segments (n=120), the rate of transmural healing was 6.4% at M1, 6.4% at M2, 13.8% at M3, 13.8% at M4, 15.6% at M5, 22.0% at M6, 28.4% at M7, 28.6% at M8, 28.6% at M9, 28.6% at M10, 32.8% at M11 and 34.4% at M12.
Among the 123 patients with CD, in multivariable analyses, absence of transmural healing (C-score > 0.5) within the first year was associated with increased risk of surgery (HR=3.37 [1.30-8.68]; p=0.012), drug discontinuation (HR=2.31 [1.29-4.14]; p=0.005), and bowel damage progression (p <0.001) while we observed a trend for higher risk of CD-related hospitalization (HR=1.92 [0.85-4.36]; p=0.11).
Conclusion
Transmural healing is achievable in more than 30.0% of active segments in patients with CD treated with anti-TNF therapy within the first year. The best time to assess transmural healing was between 6 and 12 months after starting anti-TNF therapy with higher rate of transmural healing for colorectal versus ileal segments. Transmural healing defined as C-score < 0.5 is associated with long-term improved outcomes in patients with CD.
Disclosure
Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda
