To compare the effectiveness of anti-tumor necrosis factor (TNF) medication plus methotrexate versus anti-TNF medication alone in reducing time to treatment failure and improving patient-reported outcomes in children and adolescents with Crohn’s disease
|Randomized controlled trial
|297 children and adolescents under age 21 with Crohn’s disease starting anti-TNF medication
- Anti-TNF medication plus methotrexate
- Anti-TNF medication alone
Primary: time to treatment failure (defined by failure to achieve remission, hospitalization for inflammatory bowel disease, use of steroids, or discontinuation of anti-TNF medication for lack of effectiveness or toxicity)
Secondary: patient-reported pain and fatigue
|1-year follow-up for primary outcome
This randomized controlled trial compared the effectiveness of anti-TNF medication plus methotrexate, versus anti-TNF medication alone, in reducing time to treatment failure and improving patient-reported outcomes in children and adolescents with Crohn’s disease.
Researchers randomly assigned patients to one of two groups. In the first group, patients received one of the anti-TNF medications, adalimumab or infliximab, plus methotrexate. Their doctors determined which of the two anti-TNF medications patients received. In the second group, patients received adalimumab or infliximab alone. Doctors asked patients to remain on their medications for the duration of the study.
The study included 297 children and adolescents who were younger than age 21, diagnosed with Crohn’s disease, and were starting anti-TNF medication. Of these patients, 82% were White, 11% were Black, 1% were Asian, and 4% identified as multiple or other races. The average age was 14, and 65% were male. All received care at one of 35 clinics across the United States.
Researchers defined treatment failure as failure to achieve remission, hospitalization for inflammatory bowel disease, use of steroids, or discontinuation of anti-TNF medication for lack of effectiveness or toxicity. To assess time to treatment failure, researchers reviewed patient medical records one year after patients started treatment. Researchers also contacted patients one and two years after they started treatment to assess their pain and fatigue.
Parents of children with Crohn’s disease and clinicians helped design the study.
After one year, patients who received either anti-TNF medication plus methotrexate and patients who received one of the anti-TNF medications alone did not differ significantly in time to treatment failure or patient-reported pain or fatigue.
Compared with patients who received adalimumab plus methotrexate, patients who received adalimumab alone had a shorter time to treatment failure (p=0.03). Patients who received infliximab plus methotrexate did not differ significantly in time to treatment failure from patients who received infliximab alone.
Because study enrollment was lower than expected, the study may have been underpowered to detect meaningful differences in outcomes between the groups. Also, the study only considered outcomes that were routinely assessed in clinical care and did not look at other outcomes that measure treatment effectiveness, like mucosal healing.
Conclusions and Relevance
In this study, patients who received adalimumab plus methotrexate had a longer time to treatment failure than patients who received adalimumab alone. The addition of methotrexate for patients who received infliximab did not show a benefit compared with patients who received infliximab alone.
Future Research Needs
Future research could compare the use of anti-TNF medications plus methotrexate versus anti-TNF medications alone to determine their effectiveness in treating other outcomes, such as mucosal healing.