Introduction
Ustekinumab (UST) is efficacious in inducing and maintaining remission in patients with Crohn’s disease (CD). Treatment persistence up to 5 years has been documented in open-label extension of pivotal RCTs of UST (1). In a prospective, real-world (RW) nation-wide study (REASSURE) 73% of 169 bio-naive (BN) and bio-experienced (BE) patients were still in the study after 2 years of treatment with UST (2).
Aims & Methods
In this prospective, single-centre study we aimed to assess the long-term persistence of UST treatment in consecutive BN and BE CD patients who were treated in RW setting with UST in approved dosing regimens for induction and remission maintenance.
Consecutive BN and BE CD patients with active moderate to severe luminal CD with or without perianal involvement, aged 18-80 years who received UST induction (6mg/kg iv) and maintenance (90mg sc q8 weeks) and achieved clinical and biomarker response or remission without concomitant steroids at 6 months after initiation of UST were included in a long-term observational study. Study end-point was treatment discontinuation for whatever reason. Patients were followed every 4 months with clinical examination, recording of the Harvey-Bradshaw Index (HBI) and laboratory tests [including regular CRP and occasional Fecal Calprotectin (FC)]. Ileocolonoscopy was performed at 6 months after initiation of treatment and then every 2 years. Clinical response and remission were defined as a drop in HBI ≤2 and <5 from initiation of treatment, respectively. Biomarker remission was defined as a CRP level ≤0.5mg/dL and FC ≤200 μg/g. Endoscopic remission was defined as a SES-CD score of ≤3 and a Rutgeert’s score of ≤1 for patients with inflammatory CD and for patients in post operative setting, respectively. In this abstract we report the results on the persistence of UST-treatment based on clinical and biomarker data.
Results
Between 1/6/2017 and 31/12/2024, 64 patients were evaluated and 52 patients who fulfilled the entry criteria were enrolled in the study. Patient demographic, clinical, biomarker and endoscopic data is shown in table 1. Of these 52 patients, 42 (80.7%) patients were still maintained in clinical, biomarker and endoscopic remission [HBI 2.3 (1-4), mean (range), CRP<0.5 mg/dL and FC <200μg/ml)] on UST 90 mg sc every 8 weeks for >2 [n=10 (24%),3 [n=5 (12%)], 4 [n=5 (12%)], 5 [n=6 (14%)] και ≥ 6 [n=16 (38%)] years after inclusion in the study, respectively. Treatment escalation was not performed and neither serious adverse events nor serious infections were reported in any of these patients during the study period. Ten patients (19.3%), two BN and 8 BE stopped therapy. Cessation of treatment was slightly statistically higher in BE than PN patients (p<0.05). Five of 10 patients stopped treatment because of post-operative endoscopic recurrence (Rutgeert’s score ≥i2) at 2,2,2.5, 2.9 and 3.2 years, respectively and 2 patients because of a flare of colitis at 4 and 6.5 years, respectively after inclusion in the study. Another 3 patients stopped therapy because of active axonal spondyloarthropathy 2.3 years (n=1) and two patients because they were diagnosed with pancreatic cancer and a T1-colorectal cancer (patient was on the 3nd biologic agent after a 20-year course of colitis) after 7 years in the study, respectively.
Conclusion
This prospective, open label, single-center RW study confirms the long-term treatment persistence of UST with an acceptable safety profile.
TABLE 1: Patient demographic, Clinical, and laboratory data at initiation of treatment
Patient number: n=52
Age, mean (range): 42.6 (24-79)
Males: 25 (48%)
Bio-naïve: 24 (46,15%)
Bio-experienced: 28 (53,75%)
Prior biologics (1;n=8, 2; n=10, 3;n=7), 4; n=3)
Agents received: Infliximab/adalimumab/vedolizumab/experimental agent in phase III-RCT
Years since diagnosis: 12,11 (4-31)
Smokers active/ex-/never: 24/5/23
Disease location (L1/L2/L3)/P+: (24/11/17)/10
Flare after right hemiclectomy: 17 (32.7%)
Extra-Intestinal Manifestations: 27 (52%)
Disease activity at initiation of treatment
HBI: 16.5 (9-21)
CRP (mg/dL): 8.5 (2.5-15.5)
Faecal Calprotectin: 650 (385-1850)
SES-CD: 10.4 (7-19)
Rutgeert's score: 2.43 (2-3)
Concomitant steroids: 24 patients (46.15%)
Oral prednisolone: n=18 [20 mg (15-25mg)/day]
Oral budesonide: n=6 (9mg/day)
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References
- Colombel JF, et al, Clin Gastroenterol Hepatol. 2023;S1542-3565(23)00499-8
- Mantzaris GJ et al, UEGW 2024, MP676.
Disclosure
Advisory Boards/Lectures: AbbVie, Aenorasis, Celgene, Celltrion, Dr Falk Pharma, Ferring, Hospira, Inovis, Janssen, Merck Sharp & Dohme, MYLAN, Pfizer, Takeda, και Vianex
Research support: AbbVie, Ferring, Galenica, Genesis, Merck Sharp & Dohme, MYLAN, Takeda και Vianex
