A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

Abstract

Background: Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods: Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results: Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions: Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.

Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study

“…It has been reported that serum concentrations of UST are proportional to the dose and are associated with clinical efficacy [ 7 ]. A study from Finland revealed that 39% of patients with refractory CD required UST dose optimization by shortening the medication interval time [ 10 ]. However, the efficaciousness of the drug trough concentration and the adequate administration route are still debated worldwide [ 11 – 13 ].…”

Population Pharmacokinetics and Exposure–Response Analyses of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease

“…Indeed, elevated baseline CRP was identified as an indicator of dose intensification in a recent real-world study of ustekinumab in patients with CD. 29 CL and V c in male patients were 17% higher than in female patients. Because body weight was already accounted for in the model, these effects may represent an additional layer of variability.…”

Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review

“…Among studies ONA that reported an initial maintenance dose ( n = 14), six reported a median of 29% of patients (range 9–100%) started on every-12-week dosing, while 13 out of 14 studies reported a median of 100% (range 63–100%) of patients initially started on every-8-week maintenance dosing (Fig. 2 ) [ 28 , 29 , 33 , 35 – 37 , 40 , 41 , 98 – 104 ]. The EMA recommendation, however, is to start with a lower dose regimen (e.g., 90 mg every 12 weeks) [ 105 ].…”