Remission induction with infliximab works well in paediatric Crohn’s disease
Kids with Crohn’s disease (CD) may do well to start treatment on infliximab (IFX), which has proven to be superior to conventional regimens such as corticosteroids or exclusive enteral nutrition (EEN) in terms of short-term clinical and endoscopic remission, according to the results of an open-label trial.
“While the efficacy of IFX in refractory paediatric patients with CD is well established, this [trial] now proves what was suggested in only a small number of observational cohort studies in children with CD: that first-line IFX therapy results in lower relapse rate and longer duration of remission than induction with EEN or corticosteroids,” the investigators pointed out.
Said to be the first to document the efficacy of IFX vs conventional treatment immediately after CD diagnosis, the current trial included 100 children. They were randomly assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14, and 22 (n=50) or conventional therapy (n=50; EEN or oral prednisolone 1 mg/kg, maximum 40 mg). Treatment was initiated a median of 8 days after diagnostic endoscopy.
At week 10, significantly more patients in the IFX than in the conventional group achieved clinical (59 percent vs 34 percent; p=0.021) and endoscopic remission (59 percent vs 17 percent; p=0.001). [Gut 2020;doi:10.1136/gutjnl-2020-322339]
One-year findings showed no significant between-group difference in the number of patients in clinical remission (weighted Paediatric CD Activity Index score <12.5; p=0.421). However, those on IFX were more likely to maintain remission at week 52 on azathioprine monotherapy without requiring treatment escalation (41 percent vs 15 percent; p=0.004).
Quality of life (QOL) increased for patients in both groups, from 59.3 at baseline to 79.7 at week 52 with IFX (p<0.001) and from 61.2 to 77.5 with conventional treatment (p<0.001). Meanwhile, adverse events occurred with lower frequency in the IFX group (44 percent vs 60 percent), although the difference was not significant (p=0.125). There were 15 serious adverse events recorded, including ileocecal resection, intra-abdominal abscess, and perianal abscess drainage, among others.
Despite the similar clinical remission rates at 1 year after diagnosis in both treatment groups, the investigators argued for starting IFX therapy in children with newly diagnosed moderate-to-severe CD. They pointed out that by using the drug for induction of remission, “ongoing disease activity or corticosteroids use prior to escalation to IFX in the conventional treatment group could have been prevented.”
More importantly, for children and adolescents, ineffective induction treatment strategies that lead to delay in achieving remission and frequent flare-ups in the first year after diagnosis, which look already bad, may have further adverse consequences, the investigators added.
“[It] may slow their pubertal development and affect their school attendance and general well-being, [as well as] put them at risk of developing fistulizing or stricturing complications,” they said. “[So] a maximally effective therapy from diagnosis onwards is highly desired.”
Meanwhile, some might take a dim view of implementing IFX in the first-line setting, pointing to the increased risk of side effects and higher costs. However, the investigators reiterated the safety of first-line IFX in children, with the overall incidence of adverse events within 1 year similar to that with conventional treatment and in line with findings in adults. Furthermore, the introduction of biosimilars has largely reduced the costs of IFX treatment. [Gastroenterology 2014;146:383-391; J Crohns Colitis 2017;11:289-296]
“[IFX] was well accepted by children and their parents, which shows the importance of moving forward with protocols to allow us to learn what is best. Future follow-up and additional research are needed to determine whether IFX can be stopped and for which patients this will be beneficial,” they said.