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P641 Ustekinumab efficiency as a higher-line therapy in association with serum levels in patients with Crohn’s disease

M. Kolar*1, K. Pudilova1, M. Bortlik1,2,3, D. Duricova1, K. Malickova1,4, M. Lukas1, V. Hruba1, N. Machkova1, R. Vanickova1, K. Mitrova1, M. Vasatko1, M. Lukas1,4

1ISCARE I.V.F. a.s., IBD Clinical and Research Centre, Prague, Czech Republic, 2Military University Hospital and First Faculty of Medicine, Charles University, Department of Internal Medicine, Prague, Czech Republic, 3Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 4Institute of Medical Biochemistry and Laboratory Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

Background

Ustekinumab (UST) is an anti-IL-12/23 monoclonal antibody used for treatment of Crohn’s disease (CD). We evaluated response to UST and its association with serum trough levels (TLs) in a cohort of patients from real clinical practice.

Methods

Data from consecutive CD patients who started UST between March 17 and October 18 were included. Disease activity was assessed retrospectively by Harvey–Bradshaw Index (HBI) at Week 0 and then every 8 weeks. HBI between 0–4 was considered as remission, 5–7 as mild, 8–15 as moderate, and ≥16 as severe disease activity. At Week 24, the patients with HBI decrease of ≥3 were considered as responders. C-reactive protein (CRP), faecal calprotectin (FC), and UST TLs were measured at every visit.

Results

Seventy-four patients (39% males, 61% females), mean age 36.9 years, were included. Mean disease duration was 14.5 years. In median, UST was administered as a third biologic agent. Concomitant immunosuppression (IS) was present in 43% of patients at Week 0 and 31% had systemic corticosteroids. At baseline, 7% of patients had severe disease activity, 22% had moderate, 29% mild clinical activity and 42% of patients had no disease activity. At Week 24 the proportions were 0%, 14% and 17%, and 69%, respectively. The HBI decreased from 6.4 ± 5.1 at week 0 to 4.4 ± 3.4 at Week 24 (p = 0.0430). Significantly more patients with concomitant IS at week 0 had no baseline clinical activity (63% vs. 28%; p = 0.0022); however, the proportion of patients with IS did not change until Week 24. In total, 40% of patients responded to therapy at Week 24. There was no change in mean CRP and FC between the two time points (CRP 13.2 ± 14.8 mg/l vs. 11.1 ± 13.0 mg/l, p = 0.2471; FC 1901 ± 1967 μg/g vs. 1818 ± 1972 μg/g, p = 0.5509). There was no predictive value of UST TLs at Week 8 or 16 for clinical or biochemical response at Week 24; however, patients in clinical remission at Week 24 had significantly higher UST TLs comparing to patients with clinical activity (5.9 ± 4.2 μg/ml vs. 2.7 ± 1.7 μg/ml; p = 0.0374). Patients with no or one previous biologic therapy tended to have higher TLs at Week 8 as well as lower HBI at all time points comparing to patients with two or more previous drugs, however, it did not affect the response rate. We observed multiple cases of eye redness, periorbital exanthema or other exanthema, and also increased hair loss. No patient discontinued the treatment until Week 24.

Conclusion

Despite no change in inflammatory markers, there was a clear clinical benefit of UST as a higher-line therapy for CD patients. UST TLs do not seem to predict short-term response and the usefulness of pharmacokinetic monitoring is yet to be elucidated. No adverse events requiring the treatment termination were observed.