Infliximab Therapy Makes Remission Attainable for Some Pediatric Crohn's Disease Patients

Infliximab therapy has the potential to induce remission in pediatric Crohn’s disease patients, but loss of response to the therapy remains a concern.

Infliximab holds the promise of remission and improved growth in pediatric patients with Crohn’s disease, the results of a study appearing in the October 2013 edition of Pharmaceuticals suggest.

“Moderate to severe disease is generally well controlled and growth is improved, but the biggest single potential problem is loss of response to these extremely effective drugs,” researchers from Monash University, the Royal Children’s Hospital, and the University of Melbourne wrote.

Researchers defined loss of response as worsening disease activity despite ongoing infliximab infusions.

Researchers used hospital records from The Royal Children’s Hospital in Melbourne, Australia, to quantify long-term incidence of loss of response in children receiving infliximab maintenance therapy, and the extent to which ceasing immunomodulating drugs affected loss of response rates. Noting the potential for lower weights, short stature, and reduced growth rates often observed in children with Crohn’s disease, the researchers also observed the impact of infliximab therapy on height and weight.

Researchers identified 71 participants receiving infliximab maintenance therapy who were eligible for study inclusion from the hospital records. Most participants (91.5%) were younger than 16 years at the time of diagnosis. Most of the 59 participants with available Pediatric Crohn’s Disease Activity Index Scores showed severe to moderate forms of the disease.

Several participants were receiving immunomodulating therapy at the beginning of the study, including thiopurines and methotrexate, as well as corticosteroids or budesonide, the researchers noted.

Ten weeks after the first infliximab infusion, 45 participants entered remission, whereas 10 additional patients had mild disease activity. A single patient had moderate disease activity, the researchers added.

As therapy progressed, more patients entered remission: the researchers reported 80% to 89% of patients entered remission during weeks 34 to 130 of therapy, and, by week 154, 8 of 12 patients who were still receiving therapy had entered remission.

In addition, the 13 participants receiving oral corticosteroids at the beginning of their infliximab treatment were taking a lower dose of corticosteroids by week 10 of infliximab therapy, or had ceased taking the corticosteroids entirely. Three participants receiving budesonide had also discontinued that therapy by week 10 of infliximab therapy.

Meanwhile, 39 of the 56 participants receiving immunomodulator therapy when infliximab treatment began had discontinued the immunomodulator during the study.

During the course of the study, 20 participants ceased infliximab infusions due to loss of response, researchers noted. They detected no statistical significance in rates of loss of response in participants who received immunomodulator therapy compared with patients who did not receive the therapy. Although a time-varying covariate analysis revealed an increase in loss of response following cessation of immunomodulator therapy, the researchers determined that it was not statistically significant.

They later noted that the retrospective nature of their study is less likely to determine the effect of immunomodulating drugs used in conjunction with infliximab.

“We estimated the likelihood of continuing clinical response to infliximab as 74% and 54% at 2 and 4 years, respectively,” the researchers wrote. “There was a high rate of remission and very significant reduction in the use of corticosteroids. Those who entered remission after induction were significantly less likely to experience loss of response.”

At 34 weeks after infliximab therapy began, researchers noted a significant increase in standard deviation scores for height in the 67 participants with available height and weight data, with the majority of participants continuing to see improvements in their height compared with baseline measurements.

Other variables, including disease location, immunomodulator use, baseline prednisolone use, and disease remission, were not associated with improvements in height or weight at any other time point during the study, the researchers added.

“The availability of biological agents such as infliximab has transformed the care of patients with Crohn’s disease and children in particular,” the researchers noted. “This study has demonstrated the efficacy of infliximab in ordinary clinical practice for the long-term management of this life-long illness.”