The Continental Divide: Anti-TNF Use in Pediatric IBD Is Different in North America Compared to Other Parts of the World

Abstract

Background and Aims Use of anti-TNF therapies varies internationally. As an initiative of the international Pediatric IBD Network (PIBDNet), we compared global pediatric IBD anti-TNF practice patterns. Methods Physicians were surveyed about anti-TNF use in Crohn's disease (CD) and ulcerative colitis (UC). Chi-squared, independent samples Mann–Whitney U, or related samples Wilcoxon signed rank tests were used to compare groups. Results 344 physicians treating pediatric IBD responded from 43 countries (54% North America, 29% Europe, 6% Oceania, 6% Asia, 3% Africa, and 2% South America). Respondents treated a median 40 IBD patients. CD was more commonly treated with anti-TNF than UC (40% vs. 10%, p<0.001). North Americans more often used anti-TNF (median 50% vs. 30%, p<0.001) and before immunomodulator (80% vs. 35% CD, p<0.001; 76% vs. 43% steroid-dependent UC, p<0.001). Anti-TNF monotherapy was more common in North America. Anti-TNF in combination with methotrexate, instead of thiopurine, characterized North American practices. North Americans more often continued immunomodulator indefinitely and less often adhered to standard infliximab induction dosing. Access limitations were more common outside North America and Europe for both CD (67% vs. 31%, p<0.001) and UC (62% vs. 33%, p<0.001). Conclusions Anti-TNF use in North America varies significantly from elsewhere.

Infliximab and its biosimilar produced similar first‐year therapy outcomes in patients with inflammatory bowel disease

“…The trough levels during induction were higher during 2016, and it is very likely that this reflects a change in clinical practice during this period, as studies carried out around this time reported better responses in young children with higher doses. 16,17 Disappointingly, although the trough levels during induction were higher, we did not observe any increase in the proportion of patients that maintained their therapeutic response. There were no major adverse events during the study period, no alarming signs and no acute infusion reactions with either of these drugs.…”

“…During the first year of therapy, more than one‐third of the patients discontinued the therapy, although therapy optimisation was frequent. The trough levels during induction were higher during 2016, and it is very likely that this reflects a change in clinical practice during this period, as studies carried out around this time reported better responses in young children with higher doses . Disappointingly, although the trough levels during induction were higher, we did not observe any increase in the proportion of patients that maintained their therapeutic response.…”

Real‐World Infliximab Pharmacokinetic Study Informs an Electronic Health Record‐Embedded Dashboard to Guide Precision Dosing in Children with Crohn’s Disease

“…There is a critical need for a real-world PK investigations as infliximab monotherapy is favored over combination therapy in pediatric IBD practices in North America with an alarming rate of subtherapeutic infliximab levels with as-labeled dosing. 6,17 Additionally, although the PK parameters are comparable to previously published PK models in CD, 11,18 our study has notable improvements in study design and model prediction. Specifically, we prospectively enrolled patients with CD across four medical centers and collected longitudinal blood samples to conduct a more thorough PK analysis for patients receiving infliximab monotherapy.…”

“…There is a critical need for a real‐world PK investigations as infliximab monotherapy is favored over combination therapy in pediatric IBD practices in North America with an alarming rate of subtherapeutic infliximab levels with as‐labeled dosing 6,17 . Additionally, although the PK parameters are comparable to previously published PK models in CD, 11,18 our study has notable improvements in study design and model prediction.…”

Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers

“…An increased risk for life‐threatening malignancies such as lymphoma has been also reportedly associated with thiopurine use in children with IBD 13 . Therefore, paediatric IBD specialists in North America prefer methotrexate over thiopurines for combination treatment with anti‐tumour necrosis factor agents 14 . However, there is currently a lack of evidence regarding the efficacy of methotrexate in the treatment of IBD 15,16 …”