Introduction
Crohn's disease (CD) is a heterogeneous condition with potentially complicated course. We aimed to evaluate the rates and risk factors for complicated disease course within a real-world, prospective inception cohort of patients with newly diagnosed CD (ndCD).
Aims & Methods
This prospective, longitudinal cohort study included adults with ndCD managed at a tertiary referral center. Treatment decisions were made at the discretion of the treating physician. The key outcomes were: (1) complicated-disease course - defined as CD-related hospitalization, surgery, steroid dependency, or the use of ≥2 biologics; (2) extra-complicated disease course - defined as recurrent or prolonged hospitalization (>5 days), multiple perianal procedures, intestinal resection, steroid dependency, or the use of ≥3 biologics; and (3) phenotype progression. Kaplan-Meier survival analysis was used to assess rates of complicated course over 5 years, and multivariable Cox regression models were applied to identify baseline risk factors.
Results
A total of 192 patients with ndCD were enrolled; 70% presented with an inflammatory phenotype (B1) (see Table 1). Overall, 150 patients (78.1%) were recommended to start biologic therapy, with half receiving this recommendation within 4.1 months (95% CI: 2.1-6.3) from diagnosis. Of these, 134 patients (89.3%) initiated treatment - 50% within 6 months and 63.6% within 12 months. Cumulative outcome rates at 1, 3, and 5 years post-diagnosis were: complicated course - 24.2%, 35.9%, and 51.3%, respectively; extra-complicated course - 15.6%, 20.5%, and 29.0%, respectively; phenotype progression - 1.6%, 5.5%, and 10.6%, respectively. In a multivariable analysis, patients with a progressive phenotype (B2/B3) at diagnosis had significantly increased risk for complicated (HR 3.3, 95% CI:2.0-5.7) and extra-complicated (HR 6.7, 95% CI:3.1-14.4) disease course. Additional risk factors included elevated inflammatory markers and disease extent at diagnosis. We further analysed the subgroup of 33 patients with a B1 phenotype (~25% of those with a B1 phenotype) who were not recommended biologic therapy by their treating physician. In this subgroup, the complicated course was markedly low, 3.0%, 6.3%, and 11.5% at 1, 3, and 5 years, respectively, and none developed an extra-complicated course. Notably, this subgroup exhibited significantly lower inflammatory indices (CDAI, HBI, CRP, and fecal calprotectin) at diagnosis compared to patients for whom biologics were recommended (all p<0.001).
Table 1:
| Sex, Female, n (%) | 88 (45.8) |
| Age, median (IQR) | 26 (21-36) |
| BMI (kg/m2), median (IQR) | 21.7 (19.9-25.2) |
| Never smokers, n (%) | 139 (72.4) |
| Family history of IBD, n (%) | 58 (30.2) |
| Extraintestinal manifestations, n (%) | 57 (29.7) |
Ileal (L1), n (%)
Colonic (L2), n (%)
Ileocolonic (L3), n (%) | 124 (64.6)
19 (9.9)
49 (25.5) |
| Perianal (P), n (%) | 37 (19.3) |
Inflammatory phenotype (B1), n (%)
Stricturing phenotype (B2), n (%)
Penetrating phenotype (B3), n (%) | 137 (71.4)
36 (18.8)
19 (9.9) |
Conclusion
In this real-world cohort, applying a best-practice treatment approach, over half of patients with ndCD experienced a complicated course within five years, primarily those with a progressive phenotype at diagnosis. Notably, a subset of patients with an inflammatory phenotype and low inflammatory burden had favorable long-term outcomes without biologics, underscoring the importance of early risk stratification to guide individualized treatment strategies.
