Higher ustekinumab trough levels link to increased remission in Crohn’s
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Higher ustekinumab trough concentration levels correlated with increased rates of endoscopic remission among patients with Crohn’s disease, according to research published in BMC Gastroenterology.
“With the evolved “treat-to-target” approach, the ultimate aim of CD treatment has moved from clinical remission to mucosal healing. ... Patients who achieve mucosal healing with the early use of intensive therapeutic strategies have been reported to have better long-term outcomes,” Jia-yin Yao, of the Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease at the Sixth Affiliated Hospital of Sun Yat-Sen University, China, and colleagues wrote. “Ustekinumab is a human IgG1 that targets the shared p40 subunit of IL-12 and IL-23. ... Clinical data for the use of ustekinumab in China as a CD treatment are currently insufficient, as it has only been in clinical use for 1 year.”
In a single-center, retrospective study, researchers evaluated the relationship between ustekinumab (Stelara, Janssen) trough concentration levels and endoscopic outcomes among 19 patients (mean age, 29.1 years; mean disease duration, 5.5 years) with refractory CD from the Inflammatory Bowel Disease Center of the Sun Yat-Sen Affiliated Sixth Hospital. Studied endpoints included endoscopic remission and response, clinical remission and response as well as steroid-free clinical remission at week 16. Before ustekinumab initiation, researchers noted 89.5% of patients had been exposed to prior biologic treatment, 42.1% of patients had previous CD-related surgery and 52.6% of patients had perianal diseases.
At 16 weeks after ustekinumab administration, mean CD activity index scores (220.5 vs. 92.4) and simple endoscopic scores for CD (11.2 vs. 4.4) decreased from baseline while the proportion of patients with normal C-reactive protein levels increased from 5.3% to 42.1%. Further, the rates of clinical response, clinical remission, endoscopic response and endoscopic remission were 89.5%, 84.2%, 42.2% and 73.7%, respectively.
Through predicted endoscopic remission using the receiver operating characteristic curve, researchers determined an optimal cutoff trough concentration level of 1.12 µg/mL. Compared with patients who had a lesser concentration level, those with a concentration level greater than 1.12 µg/mL had increased rates of endoscopic remission (70% vs. 11.1%), clinical response (90% vs. 88.9%), clinical remission (90% vs. 77.8%), endoscopic response (90% vs. 55.6%) and CRP normalization (60% vs. 33.3%).
“Ustekinumab is effective in treating refractory CD with confirmed efficacy both in induction and maintenance therapies. In this real-world study, we identified an ideal ustekinumab trough concentration cutoff point of 1.12 g/mL, patients with trough levels greater than 1.12 g/mL are reported to be associated with higher endoscopic remission rates,” Yao and colleagues concluded. “However, more multicenter randomized controlled trials with larger sample sizes and longer follow-up periods are warranted to provide stronger evidence for individual therapies for refractory CD.”
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