Ustekinumab yields high remission in Crohn’s disease, even for fistulizing disease

Treatment with the anti-interleukin (IL)-12/-23 monoclonal antibody ustekinumab yields a high rate of clinical remission in patients with moderate-to-severe Crohn’s disease (CD) in the real-world setting, according to a study presented at AIBD 2021. 

In the multicentre retrospective cohort study, 241 patients (mean age 39.9 years, 86 percent previously treated with at least one biologic) in Brazil who initiated treatment with ustekinumab for moderately to severely active CD were followed up on clinical, biochemical, and corticosteroid-free remission. Ustekinumab was administered as a single loading dose in the form of intravenous infusion based on weight, followed by a maintenance dose of 90 mg, given subcutaneously Q8W, 8 weeks after the initial loading dose. [AIBD 2021, abstract P008]

After 8 weeks, 66.7 percent of patients showed clinical response to ustekinumab. The primary outcome of clinical remission at 16 weeks, as defined by Harvey-Bradshaw index (HBI) ≤4, occurred in 60.2 percent of patients.

Over time, the rates of clinical remission were 51.4 percent and 24.1 percent at weeks 24 and 56, respectively, in a non-responder imputation (NRI) analysis.

Biochemical remission, as indicated by normalization of C-reactive protein (CRP) in patients whose baseline CRP levels were elevated, was seen in 61.3 percent of patients at week 16.

Almost two-thirds (59.6 percent) of patients achieved corticosteroid-free remission at their last follow-up. As a reference, 97 patients (57 percent) had received corticosteroids as induction therapy.

The researchers found that having a HBI of >9.5 at baseline, penetrating disease, and prior treatment with anti-TNF agent were factors associated with lower clinical remission rates.

There were no new safety signals detected. Thirty-nine patients (16.2 percent) discontinued treatment, mainly due to disease progression/loss of response (35.9 percent). Other reasons for discontinuation included primary failure (25.6 percent), lack of access to treatment/ lack of reimbursement (17.9 percent), and pregnancy (15.4 percent).  

Given the chronic, lifelong nature of CD, it is essential to understand the long-term outcomes of treatment to manage the disease effectively, according to experts.

“This study confirms the previous reported effectiveness and long-term maintenance of response of ustekinumab in CD patients exposed to biological therapy, especially to anti-TNF agents,” the researchers concluded.

How about perianal fistulizing disease?

In another real-world retrospective study, researchers found that the remission rates were high with ustekinumab treatment, including in those who have failed prior anti-TNF even if they have perianal fistulizing disease. [AIBD 2021, abstract P066]

The study included 34 patients (59 percent females) with CD who had failed at least one anti-TNF therapy before receiving ustekinumab induction.

Nearly three-quarters of patients (70.5 percent) achieved clinical remission with ustekinumab treatment — of which 29 percent were on concomitant steroids or immunomodulators.

Among the patients with a fistulizing disease (50 percent), 70 percent of them achieved clinical remission with ustekinumab.

Ustekinumab also led to numerical reductions in inflammatory biomarkers, as indicated by a drop in mean CRP from 2.4 at baseline to 1.98 after induction (p=0.079) and in mean faecal calprotectin from 386 to 175 (p=0.148).

“In patients with fistulizing CD, we suggest using ustekinumab for higher rates of remission after induction,” said the researchers.

“We also found that for faecal calprotectin, although an excellent surrogate of colon inflammation, compliance amongst patients remains low,” they added, noting that faecal calprotectin data was available for only 18 percent of patients.