Standard dosing with weight-based intravenous induction followed by 90 mg subcutaneous injections every 8 weeks is not effective for all patients, with real-world studies reporting that only up to one half of the patients achieve clinical remission, and up to 25% of patients achieve endoscopic remission. Ustekinumab is an IgG1κ monoclonal antibody that binds with high affinity to the p40 subunit shared by interleukin 12 (IL12) and interleukin 23 (IL23). Biomarker remission was identified as an adjunct treatment goal with fecal calprotectin (FC) being sensitive for endoscopic disease activity. Treatment goals have shifted from symptomatic improvement to a combination of endoscopic and clinical remission. Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing.Ĭrohn’s disease (CD) is a debilitating, relapsing-remitting, incurable inflammatory disease of the digestive tract. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. Dose optimization in case of non-response and the role of pharmacokinetic–pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. ![]() Ustekinumab is a monoclonal antibody used in Crohn’s disease (CD).
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