Pharmacokinetics, safety and efficacy of intravenous vedolizumab in paediatric patients with ulcerative colitis or Crohns disease : results from the phase 2 HUBBLE study

Paediatric ulcerative colitis [UC] and Crohn’s disease [CD] share many features with the adult forms of the illnesses. However, children with UC and CD also have age-related complications related to growth, development, nutrition, bone mineral density accretion and psychosocial needs.1 Unlike biological therapy in adults, where weight-based dosing is linear, in young children with a body weight <30 kg, a higher dose per kilogram may be required to achieve similar trough concentration levels.2 This highlights the importance of dose-ranging studies in paediatric inflammatory bowel disease [IBD] to determine the optimal dose in all paediatric age groups. The IBD treatment landscape has improved for children and adults since the development of biological therapy world-wide. In the USA, for example, several biologics are approved by the US Food and Drug Administration [FDA] for adults, two of which are also available for children. Intravenous [IV] infliximab [REMICADE, Janssen Biotech, Inc.] was the first to receive FDA approval for adults with UC and CD, and later for paediatric patients with IBD;3 subsequently, subcutaneous [SC] adalimumab [HUMIRA, AbbVie, Inc.] was FDA-approved for both adult and paediatric patients with UC and CD.4 IV and SC ustekinumab [STELARA, Janssen Biotech, Inc.] are FDA-approved for use only in adult, but not paediatric patients with UC and CD [currently in phase 3 trials in paediatric patients with CD and UC].5 Oral tofacitinib [XELJANZ, Pfizer, Inc.] and SC golimumab [SIMPONI, Janssen Biotech] are both FDA-approved for adult patients with UC, whereas phase 3 trials in paediatric patients with UC are ongoing.6,7 IV vedolizumab [ENTYVIO, Takeda Pharmaceuticals U.S.A., Inc.] is indicated for adults with moderately to severely active UC and CD,8 and paediatric phase 3 trials in UC9 and CD10 are now underway. Real-world studies evaluating off-label use of biologics, such as ustekinumab11,12 and vedolizumab,13–15 in the paediatric population suggest positive outcomes, but the safety and efficacy findings await confirmation from clinical trial data.In previous adult studies of IV vedolizumab, positive exposure–response relationships for clinical response and remission were demonstrated, and these relationships appeared to be steeper in patients with UC than in those with CD.16 However, an effective and safe dose of IV vedolizumab in children has yet to be determined. Data from a previously developed population pharmacokinetic [PK] model based on vedolizumab phase 3 study results in adult patients with UC or CD were used to select the dose and weight groups evaluated in this paediatric study.17 Here, we now report results of HUBBLE, a paediatric phase 2 study of IV vedolizumab, a gut-selective monoclonal anti-α4β7-integrin antibody evaluating PK, safety and efficacy of IV vedolizumab in paediatric patients with UC and CD.