Ustekinumab efficiency in association with serum levels in complicated refractory patients with Crohn’s disease

AutoriKolář M., Malíčková K., Bortlík M., Pudilová K., Ďuricová D., Lukáš M., Machková N., Hrubá V., Lukáš M.

Pracovisko: Klinické a výzkumné centrum pro střevní záněty ISCARE I.V.F. a.s., Praha, Česká republika


Objective: We evaluated response to UST in a cohort of complicated patients and its association with trough levels (TLs).

Methods: Data from consecutive patients who failed on at least one biologic were included. Disease activity was assessed by PGA from 0 (remission) to 3 (severe) at week 0 and every 8 weeks. At week 24, patients were considered as complete responders (CR) with PGA drop of at least 2 points, partial responders (PR) with drop of 1 point or no responders (NR) with 0 or negative decrease in PGA. CRP, FC and UST TLs were measured at every visit.
Results: 29 CD patients with mean age of 35.9 years were included. Mean disease duration was 15.2 years. Proximal disease was present in 24.1% of patients and the same proportion suffered from perianal disease. At baseline, 20.7% of patients had severe disease activity, 62.1% had moderate and 17.2% mild or no current disease activity. Severe activity was present in 10.7% of patients, 50% had moderate and 39.3% mild or no activity at week 8. At week 24 the proportions were 8.7%, 47.8% and 43.5%, respectively, however, there was no decrease in mean CRP and FC between the two timepoints (CRP 11.2±15.5 mg/L vs. 12.6±16.5 mg/L, p=0.8838; FC 1724±1718 μg/g vs. 1611±1830 μg/g, p=0.9277). Patients with moderate to severe disease activity had significantly lower UST TLs at both week 8 and 24 (12.9±10.1 μg/mL vs. 23.2±11.8 μg/mL, p=0.0090 at week 8 and 3.9±1.9 μg/mL vs. 7.1±3.8 μg/mL, p=0.0351 at week 24). 52% of patients experienced at least PR according to PGA decrease between baseline and week 24, while 48% didn’t respond. There was no difference in UST TLs at week 8 between patients who did and didn’t respond at week 24, however responders had significantly higher week 24 UST TLs (7.5±3.7 μg/mL vs. 3.8±1.9 μg/mL, p=0.0145).

Conclusion: Despite no decrease in inflammatory markers, over 50% of refractory CD Patients experienced clinical benefit from UST after 24 weeks which was associated with higher UST serum levels.