What's the Best New Drug for Luminal Crohn's Disease?

The top ranking drug to treat luminal Crohn's disease depended on the patient's disease status, according to a network meta-analysis.

In a pooled analysis of 40 trials involving 12,736 patients with luminal Crohn's disease, a dose of 5 mg/kg of infliximab (Remicade) ranked first in lowering the risk for clinical remission failure for all, while 600 mg of risankizumab (Skyrizi) came in second, and 45 mg of once daily upadacitinib (Rinvoq) ranked third compared to placebo:

• Infliximab: pooled relative risk (RR) 0.67 (95% CI 0.56-0.79)
• Risankizumab: RR 0.73 (95% CI 0.66-0.80)
• Upadacitinib: RR 0.75 (95% CI 0.68-0.83)

But when it came to history of biologic exposure, the same dose of risankizumab came in first in lowering the risk of clinical remission failure for both those who received (RR 0.74, 95% CI 0.67-0.82) or had not received prior biologic therapies (RR 0.66, 95% CI 0.52-0.85), reported Alexander Ford, MD, of the Leeds Teaching Hospitals NHS Trust in England, and colleagues.

For maintenance of remission, a once-daily 30-mg dose of upadacitinib ranked first after being associated with a lower risk of disease relapse (RR 0.61, 95% CI 0.52-0.72), followed by a weekly 40-mg dose of adalimumab (Humira) and a 10 mg/kg 8-weekly dose of infliximab.

"Nevertheless, blanket application of the findings of this meta-analysis should be avoided," the group wrote in Gut. "Selection of treatment should be informed by these results together with patient choice, which may be influenced by other considerations, including route of administration and convenience, as well as likelihood of adherence, and costs to the health service."

Experts who spoke with MedPage Today said the results of the analysis should be interpreted with caution.

Russell Cohen, MD, of the University of Chicago Medicine, who was not involved in the study, called the analysis a "helpful summary," but argued that "until the appropriate head-to-head trials are conducted, the information in meta-analyses alone should not be used by insurance companies or public officials to guide therapeutic interventions in Crohn's disease."

Stephen Hanauer, MD, of Northwestern University in Chicago, who also was not involved with the study, added that network meta-analyses provide low levels of evidence.

"There are newer therapies coming into use in patients with Crohn's disease that have greater tissue specificities, such as interleukin-23 blockers, that may provide more efficacy and safety compared to older TNF [tumor necrosis factor] blockers that are more systemic with greater risks of infections," he told MedPage Today.

Ford and colleagues examined data from 25 induction (n=8,720) and 15 maintenance trials (n=4,016) involving adults with moderate to severe luminal Crohn's disease.

When looking into biologics, a twice-weekly 108-mg dose of vedolizumab (Entyvio) came in first for maintenance -- specifically for those who received biologics before (RR 0.70, 95% CI 0.57-0.86) -- while a 40-mg weekly dose of adalimumab ranked first for those who did not (RR 0.59, 95% CI 0.48-0.73).

Among all induction and remission trials, none of the drugs led to any greater risk of adverse events (AEs), serious AEs, or infections versus placebo. However, more maintenance patients who received the 10 mg/kg dose of infliximab for 8 weeks discontinued because of AEs.

Study limitations included the fact that only 20 of the trials were at low risk for bias. Also, three upadacitinib trials (U-EXCEED, U-EXCEL, and U-ENDURE) have not been fully published with data unavailable on prior biologic exposure.

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