Patients With Higher Ustekinumab Trough Concentrations Have Improved Outcomes in CD

Patients with Crohn disease, more so than ulcerative colitis, with high ustekinumab trough concentrations during maintenance therapy have better clinical outcomes.

Patients with Crohn disease (CD) receiving maintenance therapy with ustekinumab may have superior outcomes with higher trough concentrations, according to results of a systematic review and meta-analysis published in Inflammatory Bowel Diseases.

Therapeutic drug monitoring (TDM) strategies have been found to improve outcomes for patients receiving infliximab. No TDM approaches have not been established for other monoclonal antibodies in the setting of inflammatory bowel diseases (IBDs).

The primary aim of this study was to assess whether a TDM approach may be effective for ustekinumab. To that end, investigators from the Mayo Clinic College of Medicine and Science searched publication databases through March 2022 for studies of patients with IBD who received maintenance ustekinumab in which trough concentrations were reported during treatment. The primary outcome was the difference in serum trough concentrations between responders and nonresponders.

A total of 14 studies were included in the review, 12 of which reported clinical remission and 7 endoscopic remission outcomes. Most studies defined clinical remission using the Harvey-Bradshaw Index (HBI); and, most defined endoscopic remission using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) instruments. Only 1 study recruited patients with ulcerative colitis (UC).

Further trials are needed to clarify the role of proactive therapeutic drug monitoring and dose adjustment of ustekinumab therapy to achieve a target trough concentration.

In CD, a higher ustekinumab concentration was observed among patients who achieved clinical remission (mean difference [MD], 1.61; 95% CI, 0.21-3.01 mg/mL) or endoscopic remission (MD, 1.22; 95% CI, 0.85-1.58 mg/mL), compared with nonremitters.

Similarly, when patients were stratified by trough concentrations, patients with either CD or UC with a concentration in the fourth quartile were more likely to achieve clinical remission compared with the first quartile (odds ratio [OR], 3.61; 95% CI, 2.11-6.20). A similar trend was observed for the outcome of endoscopic remission; however, it did not reach significance (OR, 4.67; 95% CI, 0.86-25.19).

Studies defined trough concentration cutoff rates between 1-2 mg/mL or 4-5 mg/mL. However, comparing the results of these studies did not demonstrate significant differences in predicting clinical or endoscopic remission.

The prevalence of antidrug antibodies ranged between 4.2% and 5.6% in the randomized controlled trials, and the rate in the observational studies was 1.2% when data were pooled.

The major limitation of this analysis was that there was a lack of randomized trials with the primary outcome of trough concentrations.

Study authors concluded, “For patients being treated with ustekinumab therapy for

IBD, it appears that there is an association between higher ustekinumab trough concentrations and improved outcomes, with stronger evidence to support better clinical outcomes than endoscopic outcomes. Further trials are needed to clarify the role of proactive therapeutic drug monitoring and dose adjustment of ustekinumab therapy to achieve a target trough concentration.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Vasudevan A, Tharayil V, Raffals LH, et al. Systematic review and meta-analysis: the association between serum ustekinumab trough concentrations and treatment response in inflammatory bowel disease. Inflamm Bowel Dis. Published online April 18, 2023. doi:10.1093/ibd/izad065