Introduction
Data on the effectiveness of biologic optimization within a treat-to-target (T2T) strategy are limited in Crohn's disease (CD) patients with quiescent symptoms but persistent objective inflammation.
Aims & Methods
We aimed to evaluate the real-world effectiveness of biologic optimization on objective remission within a T2T approach. We performed a retrospective cohort study of CD patients with quiescent symptoms (Harvey-Bradshaw Index <5) who underwent biologic optimization because of active disease documented by endoscopy and/or intestinal ultrasound (IUS). The primary outcome was objective remission within 18 months, defined according to the same modality at baseline and follow-up (Simple Endoscopic Score [SES]-CD ≤2 for patients who had received optimization for endoscopic activity at baseline, or bowel wall thickness <3mm for patients with IUS activity at baseline). The secondary outcome was disease clearance within 18 months, defined as combined endoscopic and IUS remission. Cumulative incidence functions were estimated using competing risks methodology, with treatment discontinuation or symptomatic relapse treated as competing events. Multivariable Fine-Gray regression was used to estimate subdistribution hazard ratios (SHR) with 95% confidence intervals (CI). Exploratory comparisons between anti-TNF (aTNF) and non-aTNF agents (ustekinumab and vedolizumab) were performed using propensity score-based covariate balancing weighting (stabilized, trimmed 1st–99th percentile), followed by multivariable Fine-Gray regression.
Results
We included 178 patients (Table 1). At 18 months, the cumulative incidence of objective remission was 29.6% (95% CI 21.1-38.2%), while the cumulative incidence of disease clearance was 11.8% (95% CI 5.4-18.1%). In multivariable Fine-Gray analysis, prior biologic exposure (SHR 0.37, 95% CI 0.13-1.04, p=0.059) and male sex (SHR 0.42, 95% CI 0.20-0.86, p=0.018) were associated with a lower likelihood of objective remission; prior biologic exposure was also independently associated with a lower likelihood of disease clearance (SHR 0.14, 95% CI 0.02-0.93, p=0.043). In the exploratory weighted analysis comparing treatment groups, post-weighting balance was adequate (all SMDs <0.1). Compared to non-aTNF therapy, aTNF was associated with a numerically higher cumulative incidence of objective remission (weighted SHR 2.09, 95% CI 0.93-4.69, p=0.075) and disease clearance (weighted SHR 2.76, 95% CI 0.63-12.0, p=0.18), although neither reached statistical significance.
Table 1. Baseline characteristics (N=178)
| Variable | Value |
| Age, years, median (IQR) | 42.2 (31.9–56.4) |
| Disease duration, years, median (IQR) | 10.2 (4.1–15.6) |
| Sex, male, n (%) | 107 (60.1%) |
| Location, L1/L2/L3, n (%) | 98 (55.1%)/5 (2.8%)/74 (41.6%) |
| Behaviour B1/B2/B3/B2-3, n (%) | 74 (41.6%)/73 (41.0%)/15 (8.4%)/16 (9.0%) |
| Perianal disease, n (%) | 46 (25.8%) |
| Prior surgery, n (%) | 128 (71.9%) |
| Prior biologic exposure, n (%) | 71 (39.9%) |
| Therapy, Anti-TNF/Vedolizumab/Ustekinumab, n (%) | 124 (69.7%)/28 (15.7%)/26 (14.6%) |
Conclusion
In clinically quiescent CD patients with persistent objective inflammation, biologic optimization achieved objective remission in approximately one-third of cases at 18 months, whereas disease clearance remained uncommon – underscoring the difficulty of reaching deep targets despite symptom control. Prior biologic exposure was a consistent independent negative predictor of both outcomes. These real-world data help define expectations for T2T after optimization and identify prior biologic exposure as a key negative predictor of success.
Disclosure
GP received consultancy fees from Alphasigma and Janssen.
CB received lecture fees and served as a consultant for Takeda, MSD, Ferring, Abbvie, Galapagos and Janssen.
ADB has received speaker’s fees from AbbVie, Galapagos, Celltrion and Pfizer.
RG has received speaker’s fees from Pfizer, MSD, Celltrion and Takeda.
AA has received consulting and/or advisory board fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Sanofi, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma; lecture and/or speaker bureau fees from AbbVie, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Sandoz, Samsung Bioepis, Takeda, Teva Pharmaceuticals; and research grants from MSD, Pfizer, Takeda and Biogen.
The remaining authors declare no competing interests.
