Avtor/Urednik		Hanžel, Jurij; Koželj, Matic; Špes Hlastec, Ana; Kurent, Tina; Sever, Nejc; Zdovc, Jurij; Smrekar, Nataša; Novak, Gregor; Štabuc, Borut; Grabnar, Iztok; Drobne, David
Naslov		Ustekinumab concentrations shortly after escalation to monthly dosing may identify endoscopic remission in refractory Crohn's disease
Tip		članek
Vol. in št.		, št. Vol. 33
Leto izdaje		2021
Obseg		str. e831-e836
ISSN		1473-5687 - European journal of gastroenterology & hepatology
Jezik		eng
Abstrakt		Objectives: Some patients with Crohn’s disease do not achieve remission with the approved maintenance dosing of ustekinumab every 8 weeks, possibly due to insufficient drug exposure. We aimed to study the exposure-response relationship for endoscopic remission and biomarker normalization with ustekinumab dose escalation to every 4 weeks. Methods: Out of 135 consecutive patients, 44 with active Crohn’s disease despite standard maintenance dosing [at least one of C-reactive protein (CRP) >5 mg/L, fecal calprotectin >100 mg/kg, simple endoscopic score (SES) for Crohn’s disease >3] underwent dose escalation to every 4 weeks. Subsequent endoscopic remission (SES-CD r3 without ulceration) and biomarker normalization were compared against ustekinumab concentrations. Results: Dose escalation led to endoscopic remission in 28.6% (8/28), CRP normalization 29.2% (7/24) and fecal calprotectin normalization 51.7% (15/29) of patients. Ustekinumab concentrations after escalation were higher in patients with endoscopic remission (6.90 vs. 4.29 mg/L; P = 0.025) and fecal calprotectin normalization (6.65 vs. 3.74 mg/L; P = 0.001). A threshold of 6.00 mg/L identified endoscopic remission [area under the receiver operating curve (AUROC): 0.775; 95% confidence interval (CI), 0.551‐0.999), a threshold of 4.40 mg/L (AUROC 0.755; 95% CI, 0.545‐0.964) two months after escalation identified patients with fecal calprotectin normalization at the end of follow-up. Concentrations <3.5 mg/L after escalation precluded endoscopic remission or biomarker normalization. Conclusion: Endoscopic remission was associated with higher ustekinumab concentrations after dose escalation. Patients with concentrations <3.5 mg/L after dose escalation are unlikely to achieve endoscopic remission or biomarker normalization.
Deskriptorji		Crohnova bolezen