Methotrexate proven safe, effective as first-line immunomodulator in paediatric Crohn's disease

Use of methotrexate (MTX) appears safe and effective as first-line immunomodulator for maintenance therapy in children with Crohn’s disease (CD), suggests a study presented at the 54th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN 2022).

“MTX has been used as maintenance therapy of CD in both adults and children,” according to the researchers from the Department of Paediatrics at Seoul National University Hospital in South Korea. “However, there are only a few studies on the therapeutic role of MTX as first-line immunomodulator in thiopurine-naïve CD patients and no study in children.”

Sixty-two patients with CD aged 6‒18 years and treated with MTX as first-line immunomodulator for maintenance therapy between May 2011 and May 2021 were enrolled in this retrospective cohort study. The researchers assessed clinical remission (CR) and mucosal healing (MH) at week 26 and 52, respectively. They also evaluated the Paris classification in all participants.

Sixty paediatric CD patients (mean age 13.5 years, 42 boys) had used MTX for >26 weeks, of whom 18 (30.0 percent) achieved CR, while 16 (66.7 percent) had MH at week 26; 14 (27.5 percent) and nine (81.8 percent) patients achieved CR and MH, respectively, at week 52. [ESPGHAN 2022, abstract G-P-324]

Comparisons of subtypes based on the Paris classification revealed a significantly higher CR rate in P0 patients without perianal disease (n=7, 63.6 percent) than in P1 patients with perianal disease (n=11, 22. 4percent) at week 26 (p=0.012). However, no significant difference in CR rate was seen between the P0 (n=4, 44.4 percent) and P1 subgroups (n=10, 23.8 percent) at week 52 (p=0.236).

CR and MH rates did not significantly differ in other subgroups including age at diagnosis, location, behaviour, and growth at weeks 26 and 52, respectively (p>0.05 for all).

The researchers also analysed the safety of MTX in 62 paediatric CD patients, including two who had used MTX for <26 weeks. They recorded adverse effects in 29 patients (46.71 percent), including nausea (8.1 percent), leukopaenia (8.1 percent), increase in liver enzymes (40.3 percent), skin erosion (1.6 percent), and headache (1.6 percent).

“Only one patient (1.7 percent) stopped MTX therapy due to severe nausea and persistent leukopaenia as drug adverse effect,” the researchers added.

Laboratory results

The number of patients who had used MTX as first-line immunomodulator without recurrence was 40 at 12 weeks, 24 at 26 weeks, and 11 at 52 weeks.

The researchers then compared laboratory results and Paediatric Crohn’s Disease Activity Index (PCDAI) at 14, 26, and 52 weeks with prior baseline database between patients on MTX without recurrence and those on step-up medication.

Erythrocyte sedimentation rate (ESR; ‒31.2 mm/h), C-reactive protein (CRP; ‒1.8 mg/dl), white blood cell (WBC; ‒3,718.5 per μl), and neutrophil count (‒329.4 per μl) was significantly reduced in the first 14 weeks, but not at weeks 26 and 52.

Likewise, calprotectin (–530.4 mg/kg) and PCDAI (–7.7) decreased at 14 weeks, but the reduction seen at weeks 26 and 52 did not reach statistical significance.

“Major laboratory and PCDAI changes were observed at 14 weeks that the period of use of the induction therapy and MTX treatment concurrently,” the researchers said. “Although it is not statistically significant, decreases of ESR, CRP, WBC neutrophil count, calprotectin, and PCDAI were verified from 14 weeks until week 52.”

These findings suggest that MTX is effective in maintaining the induction status of paediatric patients with CD.