Introduction
Long-term VDZ outcomes in real-world cohorts have mostly focussed on 1-year follow-up, with the longest reporting outcomes at 2-years. However, most of these studies include biologic exposed patients and also report limited data on objective markers of inflammation.
Aims & Methods
We performed a retrospective, observational, cohort study. All adult UC/IBDU patients who ever received VDZ complete induction from 2014 to December 2021 were included. Baseline phenotype and follow-up data were collected via review of electronic medical records.
The primary outcome of this study was VDZ persistence. Secondary outcomes included: clinical (partial Mayo <2), biochemical (CRP <5 gr/L) and faecal biomarker (faecal calprotectin <250 µgr/gr) remission at 1,3 and 5 years; hospitalisation, steroid prescription, surgical rates; predictors of VDZ persistence; and serious adverse events.
Results
We included 290 patients (UC n=271 [93.4%], IBDU n=19 [6.6%]), median time on VDZ 27.6 months (IQR 14.4-43.2). VDZ persistence at first year was 80.7%, 64.4% at two years, 56.5% at 3 years, 49.5% at 4 years, 47.9% at 5 years and 41.5% at 6 years. Median time to discontinuation was 14.1 months (IQR 7.0-23.3 months). Reasons for drug discontinuation: 51(17.6%) primary non-response, 63 (21.7%) secondary loss of response [8 (2.8%) during the first year; 33 (11.4%) between the first and second year; 13 (4.5%) between the second and third year; 5 (1.7%) between the third and fourth year and 4 (1.4%) over the fourth year], 9 (3.1%) adverse event, 4 (1.4%) remission and 6 (2.1%) other reasons. Multivariable Cox Regression model found previous exposure to one biologic/small molecule (HR 1.52, 95% CI 1.03-2.22, p=0.033); two or more biologic/small molecule (HR 2.37, 95% CI1.37-4.09, p=0.002), steroid at baseline (HR 1.57, 95%CI 1.08-2.29, p=0.019), left-side colitis (HR 2.80, 95% CI 1.11-7.09, p=0.029), extensive colitis (HR 3.32, 95%CI 1.34-8.21, p=0.010) and disease duration ≥ 10 years (HR 0.60, 95%CI 0.43-0.86) were independent predictors for VDZ persistence (Table 1). Clinical, biochemical and faecal biomarker remission at year 1 were 171/226 (75.7%), 157/217 (72.4%) and 127/181 (70.2%); at year 3, 83/92 (90.2%), 78/91 (85.7%) and 52/59 (88.1%) and at year 5, 23/25 (92%), 23/26 (88.5%) and 15/17 (88.2%) respectively. During follow-up, steroid prescription was needed in 98 (33.8%), hospitalization 45 (15.5%) and surgery 10 (3.4%). Serious adverse events were 1.2 per 100 patient-year follow-up.
| Variable | Univariable Cox Regression | Multivariable Cox Regression |
| Hazard Ratio | 95% CI | p | Hazard Ratio | 95% CI | p |
| Disease duration ≥ 10 years | 0.57 | 0.41-0.84 | 0.002 | 0.60 | 0.43-0.86 | 0.005 |
Disease extension
- E1: distal (reference)
- E2: left side
- E3: extensive |
2.72
2.94 |
1.08-6.83
1-19-7.23 |
0.022
0.034
0.019 |
2.80
3.32 |
1.11-7.09
1.34-8.21 |
0.030
0.029
0.010 |
Number of previous biologic/small molecule
- None (reference)
- One
- Two or more |
1.53
2.26 |
1.05-2.22
1.31-3.88 |
0.004
0.028
0.003 |
1.52
2.37 |
1.03-2.22
1.37-4.09 |
0.003
0.033
0.002 |
| Concomitant steroids at baseline | 1.67 | 1.16-2.42 | 0.006 | 1.57 | 1.08-2.29 | 0.019 |
| Partial Mayo ≥ 2 at baseline | 1.81 | 1.11-2.94 | 0.017 |
|
Conclusion
VDZ effectiveness is durable and its persistence is influenced by disease duration, previous exposure to biologics/small molecules, disease extension and steroids at baseline. Long-term VDZ safety is confirmed in our study.
Disclosure
Beatriz Gros has served as a speaker for Abbvie, Jansen, Takeda, Pfizer and Galapagos.
Nikolas Plevris has served as a speaker for Janssen, Takeda and Pfizer.
Professor Charlie Lees has acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, Galapagos, Bristol Myers Squibb, B.I., Sandoz, Novartis, GSK, Gilead, Vifor Pharma, Dr Falk, Trellus Health and Iterative Scopes; he has received speaking fees and travel support from Pfizer, Janssen, Abbvie, Galapagos, MSD, Takeda, Shire, Ferring, Hospira, and Dr Falk.
Gareth-Rhys Jones has served as a speaker for Takeda, Janssen, Abbvie and Ferring.
Lauranne Derikx has served on advisory board for Sandoz and as a speaker for Janssen.
Colin Noble has acted as a consultant to Galapagos.
None of the other authors reported any conflicts of interest.