First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn’s disease: an open-label multicentre randomised controlled trial

Abstract

ObjectiveIn newly diagnosed paediatric patients with moderate-to-severe Crohn’s disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment.DesignIn this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3–17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis.Results100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004).ConclusionsFL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy.Trial registration numberClinicalTrials.gov Registry (NCT02517684).

Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine

“…starting with the most potent treatment first) with step-up (starting with milder treatments) therapeutic approaches are insufficient to fully support this assumption. Whilst top-down approaches have been shown improved short-term prognosis possibly related to the more aggressive immunosuppression resulting in faster control of the inflammation [ 18 ], long-term outcome does not appear to be superior compared to a step-up approach [ 19 ]. Taken together, there is insufficient evidence in support of any currently available medical treatment being capable of altering (i.e.…”

Combination Immunotherapy Use and Withdrawal in Pediatric Inflammatory Bowel Disease—A Review of the Evidence

“…While pediatric data on specific calprotectin cutoff levels and relapse risk post step-down are sparse, a level below the 100 mcg/g associated with “deep healing” in this population would be in keeping with the evidence around improved outcomes post withdrawal in the context of presumed mucosal healing ( 57 ). Pragmatically, pediatric patients with more severe disease—especially those diagnosed at a younger age that have extensive disease, growth failure, fistulizing or perianal phenotypes, steroid refractoriness, and previous surgical resection in CD—will benefit most from early combination therapy and subsequent delayed withdrawal ( 1 , 7 ). Predictors of severity of outcomes in PIBD have recently been more clearly delineated ( 58 , 59 ).…”

“…Given recent advances in the management of inflammatory bowel disease (IBD), a higher proportion of patients are being exposed to both biological and immunomodulator therapies earlier in their treatment course and for longer periods of time. First-line anti-tumor necrosis factor alpha (anti-TNF) treatment with infliximab (IFX) (so-called “top-down” strategy) for children with moderate-to-severe Crohn's disease (CD), for instance, has recently been shown to convey advantages over conventional therapy in a 2020 randomized control trial (RCT) ( 1 ). While evidence-based guidelines have been developed outlining the concomitant use of anti-TNF agents and immunomodulators [including thiopurines and methotrexate (MTX)] in both adult and pediatric populations, there exists a paucity of data guiding evidence-based strategies for their subsequent withdrawal in pediatric patients who enter sustained remission ( 2 – 5 ) ( Table 1 ).…”

Antibiotics in pediatric inflammatory bowel diseases: a systematic review

“…In addition to low treatment adherence, a range of adverse effects such as growth retardation, reduced bone mass index, increased risk of infections and malignancy are associated with current medical treatments given in IBD [18][19][20][21][22]. Moreover, sustained remission rates of all currently available drugs do not surpass 40% and even in responders breakthrough flares are not uncommon [19,[23][24][25][26]. Adding to this, persistent inflammation can progress to complications such as strictures, abscesses, and fistulae, which often require surgery in CD, whereas development of acute severe colitis in UC can necessitate a colectomy [27].…”