Escalating Stelara Dose Possible in Unresponsive Crohn's

AUSTIN -- Dose escalation of ustekinumab (Stelara) should be considered for patients with Crohn's disease and manifestations of the condition, a researcher said here.

Among 38 adults with Crohn's disease, 60% improved with a 90-mg dose increasing in frequency from every 8 weeks to every 4 to 6 weeks, indicated through a composite measure of steroid-free clinical response, as well as biochemical, endoscopic, and radiologic response, reported Jason Glass, MD, of the University of Texas Southwestern Medical Center in Dallas.

Moreover, among 24 patients with perianal disease, half (50%) demonstrated improvements across a median 4.5 months, he said at the annual Crohn's & Colitis Congress (CCC).

"Ustekinumab has shown efficacy in induction and maintenance of moderate to severe Crohn's disease, but data on dose escalation of ustekinumab are limited, particularly with perianal disease," Glass said during a CCC presentation of top clinical abstracts. "Our data supports the use of dose escalation of ustekinumab for Crohn's disease."

Ustekinumab, administered through an induction dose followed by 90-mg subcutaneous maintenance injections every 8 weeks, was approved by the FDA in 2016 for the treatment of moderate-to-severe Crohn's disease. It's efficacy was previously demonstrated among Crohn's disease patients, regardless of their prior exposure to anti-tumor necrosis factor (TNF) agents.

But while there have been some studies evaluating therapeutic drug monitoring with infliximab (Remicade) for patients with inflammatory bowel disease (IBD), less is known about how best to monitor ustekinumab and the other novel biologic agents, said CCC session moderator Edward Barnes, MD, MPH, of the University of North Carolina at Chapel Hill.

Barnes cited recent guidelines that recommend a maintenance dose of 4.5 μg/mL ustekinumab for patients with Crohn's disease to achieve an endoscopic response.

"We know these patients have low levels -- that's why they dose-optimized them," Barnes told MedPage Today.

"What would be really helpful to know is, of the people who did get better, what was their dose," he said, and whether the dosing in this study matched the 4.5 μg/mL level previously established.

For this study, Glass and colleagues retrospectively enrolled patients prescribed ustekinumab between 2016 and 2019. Whether patients were optimized to a 4- or 6-week track was up to the physicians' discretion, Glass said.

In the cohort (50% male; median age 38; 76% white), 63% had perianal disease and 65% had prior IBD-related surgeries; the duration of disease was a mean 18 years. Most had an aggressive phenotype of Crohn's disease, including penetrating or fistulating disease, Glass said.

Nearly all had failed prior therapies, most commonly anti-TNF (92%), integrin (74%), or thiopurine (74%) agents, followed by methotrexate (44%), Glass reported. About a quarter (26%) were on steroids at the time of dose escalation initiation, and 13% and 18% were on thiopurines and methotrexate, respectively.

Among 23 patients with lab data available, median ustekinumab troughs were 1.3 μg before escalation began, and other indicators of inflammation were elevated as well, including a median calprotectin level of 340 μg/mg and median C-reactive protein (CRP) level of 9.55 mg/L, Glass said.

Overall, 47% of patients did not respond to on-label dosing; 28 patients (74%) were escalated to every 4-week dosing and 10 (26%) were started on 6-week dosing.

Six of 10 (60%) patients on steroids at initiation achieved a steroid-free response, while eight of 11 (73%) with endoscopic data showed endoscopic improvement and six of 12 (50%) showing radiographic improvement, Glass reported. Nine of 33 (27%) with CRP values stabilized after dose escalation, Glass reported.

Patients with less time since their disease was diagnosed were even more likely to respond to dose escalation compared with those who had longer duration of disease (P=0.047), he added.

Notably, three patients (7%) underwent IBD-related surgery after the adjusted dosing and one case each of Clostridium difficile and injection site erythema occurred, Glass reported.

Comment