Biologics for Crohn’s Go Head to Head

Ustekinumab (Stelara) or adalimumab (Humira) were similarly effective as induction or maintenance therapy for moderate to severe Crohn’s disease, according to the randomized SEAVUE trial.

In an intention-to-treat analysis involving over 350 biologic-naive Crohn’s disease patients, ustekinumab didn’t improve the rate of clinical remission (Crohn’s Disease Activity Index [CDAI] score less than 150) at week 52 compared with adalimumab (65% vs 61%, P=0.42).

Both monotherapies — which have different mechanisms of action — were safe, with data consistent with prior reports, reported Bruce Sands, MD, MS, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues in The Lancet.

“As the number of therapeutic options for Crohn’s disease grows, rigorous evidence from direct comparisons in blinded, randomized controlled trials such as SEAVUE are becoming increasingly important in selecting the right treatments for our patients,” said Sands.

Ustekinumab and adalimumab patients, respectively, achieved similar outcomes at 52 weeks for the following endpoints:

• Corticosteroid-free clinical remission: 61% vs 57%
• Clinical response: 72% vs 66%
• Endoscopic response: 42% vs 37%
• Endoscopic remission: 29% vs 31%
• Symptom remission based on patient-reported outcomes (PRO-2): 57% vs 55%

Similar early clinical remission rates were also achieved at 16 weeks (57% vs 60%).

“It makes the choice of therapy in our ever-changing payor landscape somewhat easier, as both therapies work safely and well for our Crohn’s patients,” commented Sandra El-Hachem, MD, of the Allegheny Center for Digestive Health in Pittsburgh, whose center was involved in SEAVUE.

“The clinical remission rates were strikingly high for both biologics in this study with a treat-through design, relative to the original placebo-comparator maintenance studies, even when considering the biologic-naive subgroups alone,” Jack Satsangi, MD, PhD, and PhD student Thomas Chapman, both of the University of Oxford in England, stated in an accompanying editorial. “This difference is explained in part by the SEAVUE study population, who mostly had a history of short and uncomplicated disease course, which might be more responsive to early biologic therapy.”

“There are still other reasons why a physician may choose one medication over the other, but efficacy may not be the reason,” said Adam Ehrlich, MD, MPH, from Temple University in Philadelphia, who was not involved in this study. “I think it also shows that the ‘older’ biologics like adalimumab still stand up well to the newer ones.”

The tumor necrosis factor inhibitor monoclonal antibody adalimumab was approved for treatment of Crohn’s disease in 2014, while ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, gained that indication in 2016.

Prior trials have shown higher clinical remission achieved with the use of ustekinumab or adalimumab compared with placebo, but SEAVUE is the first trial to use an active comparator with a “treat-through design” — integrating induction and maintenance therapy phases — to assess the safety and efficacy of ustekinumab and adalimumab for moderate to severe Crohn’s disease.

For this international study, Sands and colleagues enrolled 386 adults with moderate to severe Crohn’s disease and randomized them to receive ustekinumab (n=191) or adalimumab (n=195) for 56 weeks in a double-blind manner. For ustekinumab, patients received a 6 mg/kg IV dose on day 0, followed by 90 mg subcutaneous doses once every 8 weeks. Subcutaneous adalimumab was administered at 160 mg on day 0, 80 mg at 2 weeks, then 40 mg doses once every 2 weeks.

Enrollment criteria included a CDAI of 220-450 for at least 3 months (mean score of 300-302 at baseline), lack of response to or intolerance of conventional therapy (or corticosteroid dependence), at least one ulcer, and no prior biologic treatment.

Relatively few patients from the ustekinumab and adalimumab groups discontinued the study before week 52 (15% vs 24%).

Mean age in the cohort was 37, and 51-53% of participants were women. Nearly all participants were white, and average Crohn’s disease duration was slightly over 5 years. About 53-54% had disease involvement in the ileum and colon. Over one-third were on corticosteroids, including budesonide at baseline. About 35-40% had previously failed corticosteroids and immunomodulators. Mean follow-up duration was 46-48 weeks.

Serious adverse events occurred in 13% and 16% in the ustekinumab and adalimumab groups, respectively. Serious infections rates were similar between groups (2% vs 3%). The most common treatment-emergent events included Crohn’s disease events (12-16%), abdominal pain (8-13%), and headache (7-12%). No patients died.

The authors acknowledged limitations to the data, including that the findings might not be generalizable to those who previously failed biologics, have less severe disease, or a longer disease duration.

The editorialists reiterated the question of extrapolation to biologic-experienced patients, “who usually show lower response rates with further biologic therapies.”