• Infliximab is not linked to malignancy in paediatric IBD

    Hyams, Jeffrey S., et al. “Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease.” Gastroenterology (2017).


    According to a recent study published, treatment with infliximab for IBD in children is not associated with an increased risk of malignancy or hemophagocytic lymphohistiocytosis (HLH). Patients with HLH have cells of the immune system called T and NK cells that don’t work properly. These cells become overactive, causing too much inflammation. Ordinarily, these cells should destroy infected, damaged cells of the body. In HLH, the immune system begins to damage the patient’s own tissues and organs, including the liver, brain and bone marrow where blood is made. The risk of HLH in patients with IBD is increased in the setting of systemic inflammation and exposure to immunosuppressive therapy.

    The link between IBD and intestinal malignancies are well established. However, prior reports on the risk of malignancy and HLH associated with treatment for paediatric patients with IBD are limited to mainly retrospective studies with small sample sizes and/or limited duration of follow-up, systematic reviews of data pooled across multiple studies, or case series.

    Dr. Jeffrey Hyams of Connecticut Children’s Medical Center in Hartford and colleagues including paediatric gastroenterologists in the UK, investigate the risk of malignancy and lymphoproliferative disorders, including HLH in paediatric patients with IBD exposed to infliximab and compared incidence rates with patients not exposed to biologics.

    The team collected and analyzed data from 5766 patients aged 17 years old or younger from 2007 to 2016. The patients were taking part in a multicentre, prospective, cohort study (DEVELOP) of long-term safety and clinical outcomes in paediatric patients with Crohn’s disease, ulcerative colitis or unclassified IBD treated with infliximab and/or other medical therapies for IBD.

    Nearly half received one or more biologics, including infliximab (94.6%), adalimumab (34.0%) and certolizumab (5.1%). In addition to the anti-TNF alpha therapy, 232 of these patients were exposed to non-anti-TNF alpha therapies including vedolizumab (78.9%), ustekinumab (18.1%), and natalizumab (9.1%).

    There were 15 cases of malignancy over the course of the study, and all five of the patients who developed HLH had been exposed to thiopurine. Four patients were exposed to thiopurines in the absence of biologics and all five cases of HLH occurred during active thiopurine therapy. Ten patients were exposed to infliximab; of these, five were also exposed to adalimumab, six were also exposed to methotrexate, and nine were also exposed to thiopurines.

    The researchers state “13 of the 15 patients with malignancies were exposed to thiopurines; and the majority of these patients developed malignancy after less than 5 years of thiopurine exposure.”

    Calculated standardized incidence ratios did not demonstrate an increased risk of malignancy among patients exposed to infliximab versus patients not exposed to a biologic agent. This was the case even when patients were classified by thiopurine exposure.

    DEVELOP is the largest prospective study of safety outcomes in paediatric patients with IBD to date. The results suggest no increased risk of malignancy with infliximab treatment. Furthermore, the data demonstrate a trend toward an increased risk of malignancy in thiopurine-exposed patients, irrespective of biologic exposure.

    Although malignancy events in the paediatric IBD population are rare, this study has significant impact and will inform the clinician’s decision-making process in formulating treatment plans for children with IBD, especially in terms of communicating the risks of different therapies to patients and families weighing the potential benefits and risks of thiopurines in the treatment of children with IBD.

    Dr Protima Amon
    IBD CICRA Fellow
    The Royal London Hospital
    Department of Paediatric Gastroenterology