Ustekinumab Trough Levels Predicting Laboratory and Endoscopic Remission in Patients with Crohn’s Disease

Abstract

Backgrounds: Optimal concentration of ustekinumab (UST) predicting endoscopic remission has not been fully investigated in Crohn’s disease (CD). We aimed to identify the optimal UST trough levels predicting clinical, laboratory and endoscopic remission in CD patients. Methods: Twenty-eight patients with CD were enrolled and investigated (27 patients by enteroscopy and 1 by colonoscopy). The endoscopic activity was assessed using the modified Rutgeerts scoring system. Serum UST trough levels and anti-UST antibodies (AUAs) levels were determined by in-house immunoassays. Results: Endoscopic activity was negatively correlated with serum UST trough levels (Spearman’s rank correlation coefficient (ρ) = -0.66, P=0.0001) and serum albumin levels (ρ=-0.60, P=0.0007). The endoscopic activity was positively and significantly correlated with CRP (ρ=0.59, P=0.0009) and ESR (ρ=0.44, P=0.033). There was no significant association between the endoscopic score and AUA levels and/or Crohn’s disease activity index (CDAI). Serum UST trough levels and albumin levels were significantly higher in the endoscopic remission group (scores of 0 and 1) than in the non-endoscopic remission group (UST trough, mean 3.3 vs. 1.8μg/mL). No significant difference was observed in AUAs between the endoscopic remission and non-remission groups. Receiver operation curve (ROC) analysis revealed that the optimal cutoff value of UST trough levels predicting normal CRP and serum albumin levels was 1.7μg/mL for each, and the optimal cutoff value predicting endoscopic remission was 2.0μg/mL (AUC: 0.80, 95%-CI: 0.64-0.96). Conclusion: Endoscopic remission requires higher UST trough levels than those needed to normalize CRP and serum albumin levels.

Exacerbation of Atopic Dermatitis Associated with Ustekinumab Treatment in Crohn's Disease

“…Mucosal inflammation has been suggested to mediate ustekinumab pharmacokinetics as well. [11]. In patients with Crohn's disease who were refractory or intolerant to anti-TNF therapy, Battat et al observed mean ustekinumab trough concentrations of 4.7 and 3.8 μg/mL in patients with and without endoscopic response, respectively, while on maintenance therapy of ustekinumab 90 mg primarily every four weeks (42 of 56 patients) [12].…”

“…In patients with Crohn's disease who were refractory or intolerant to anti-TNF therapy, Battat et al observed mean ustekinumab trough concentrations of 4.7 and 3.8 μg/mL in patients with and without endoscopic response, respectively, while on maintenance therapy of ustekinumab 90 mg primarily every four weeks (42 of 56 patients) [12]. Finally, increased mucosal inflammation has been proposed to decrease ustekinumab trough levels by increased production of IL-12 and IL-23, which then consumes ustekinumab [11]. Numerous studies which exhibit that intensifying ustekinumab decreases loss of response in Crohn's disease patients support this mechanism [13][14][15][16][17].…”