Dr Falk Best IBD Poster
Infliximab Treatment Failure in Children with Crohn’s disease- is it avoidable?
Rulla Al-Araji, Wolfram Haller and Rafeeq Muhammed.
Birmingham Children’s Hospital
Infliximab is an effective treatment for patients with Crohn’s disease, however experience in adult IBD patients show treatment failure occurring in many patients in the first year of treatment.
We aimed to identify proportion of children with Crohn’s disease failing Infliximab therapy in the first 12 months after treatment initiation with Infliximab. We have analysed the relationship between Infliximab levels, anti-Infliximab antibodies and non-response at week 14 and week 54.
Retrospective chart review of 100 consecutive children with Crohn’s disease commenced on Infliximab as their primary biologic therapy. Serum infliximab levels were measured using an in-house ELISA method. Anti-infliximab antibodies (both free and drug bound) were measured using a commercial kit.
100 consecutive children (male: female 2:1 median age 12.4 years range 2.2-16 years) with Crohn’s disease (L1 16%, L2 29%, L3 52% Perianal disease 3%) received Infliximab as their primary biologic treatment. 89 were on Infliximab combination therapy with Azathioprine. 2 patients had severe infusion reaction during induction, hence their treatment with Infliximab was discontinued. 69/98 (70%) patients were in steroid-free clinical remission at week 14. 61/98 (62%) children had Infliximab levels measured at week 14 (median 4.8 microgram/ml range 0.4-10). By week 54, 92 patients remained on Infliximab treatment. 69/92 (75%) had Infliximab level measured at week 54 (median 5.15 microgram/ml range 0.4-10). 77/98 (79%) patients were in steroid-free clinical remission at week 54. Rates of steroid-free clinical remission, therapeutic levels of Infliximab, anti-Infliximab antibody positivity at week 14 and 54 are summarised in Table 1.
22/29 (76%) patients not in clinical remission at week 14 continued to remain on Infliximab at week 54 with 16/22 (73%) achieving steroid-free clinical remission. 19/22 (86%) patients received Infliximab with dose and/frequency escalation and 15 of these 19 patients (75%) patients achieved steroid-free clinical remission at week 54. Of the 69 patients who achieved steroid-free clinical remission at week 14, data on clinical remission at week 54 was documented only in 62 patients. 57 of these 62 patients (92%) remained in steroid-free clinical remission at week 54 on treatment with Infliximab, with 32 patients (52%) receiving Infliximab on increased dose and/frequency.
Approximately 80% children with Crohn’s disease commenced on Infliximab therapy remained in steroid-free clinical remission at week 54. Infliximab levels in therapeutic range at week 14 and 54 showed statistically significant association with clinical remission in children with Crohn’s disease. Anti-Infliximab antibodies did not tend to affect the rate of clinical remission, however a large proportion of patients were treated with increased dose and/frequency of Infliximab. Standard dose of Infliximab induction regime did not result in therapeutic levels of Infliximab at week 14 in 25% patients. Majority of patients not in clinical remission at 14 responded to Infliximab treatment with increased dose and/frequency and achieved clinical remission by week 54.