TBA (23W106)

Adjunctive methotrexate in the management of anti-infliximab antibodies in paediatric IBD

Author(s)

Ali Raba1, Sarah Kasha1, Sarah Cooper1,2, Anna Dominik1,2, PIBD Specialist Nurse Team1, Lorraine Stallard1, Shoana Quinn1, Emer Fitzpatrick1,3, Annemarie Broderick1,3, Billy Bourke1,3, Emily Stenke1, Séamus Hussey1-4

Department(s)/Institutions

1- National Centre for Paediatric Gastroenterology and Hepatology, CHI-Crumlin, Dublin 2- DOCHAS Study, CHI, Dublin 3- Department of Paediatrics, School of Medicine, UCD, Dublin 4- Department of Paediatrics, RCSI, Dublin

Introduction

Anti-TNF therapy is a highly effective therapy for inflammatory bowel disease (IBD) but anti-drug antibodies (ADAs) limit its durability and effectiveness.

Aims/Background

The aim of this study is to investigate whether adding methotrexate co-immunosuppression following antibody development abrogates titre progression and averts secondary loss of response in children diagnosed with IBD.

Method

We analysed the data of participants of the DOCHAS study of children with IBD who commenced on infliximab between January 2020 to December 2022. Clinical characteristics, disease phenotype, clinical activity indices, infliximab dose/kg, infusion frequencies and corresponding trough and anti-drug antibody levels and titres were analysed. Outcomes including secondary loss of response, medication durability and ADA titres were compared between groups with and without adjunctive methotrexate therapy.

Results

Between January 2020 to December 2022, 373 patients were newly diagnosed with IBD; 184 (50%) patients commenced infliximab (median age at diagnosis 13 years; 108 (59%) male) and 33/184 (18%) developed ADAs (14 (42%) within 6 months of starting infliximab, 7 (21%) between 6months and 1 year and 2 (6%) after more than 1 year). Adjunctive methotrexate was commenced in 20/184 (11%) patients: 18/20 for positive ADAs, and 2 for suboptimal therapeutic response to infliximab. Reduced ADAs were seen in 11/18 (61%), infliximab dose was increased in 3/18 (17%), 1 had infliximab reinduction (6%) ), but no improvement was seen in 7 (39%). By comparison, of the 15 patients with ADAs who did not start methotrexate, 3/15 (20%) lost infliximab response, ADAs improved in 2/15(13%) spontaneously, in 3/15 (20%) after infliximab dose increases, and 1/15 following reinduction of infliximab.

Conclusions

Anti-infliximab antibodies developed in less than 1 in 5 patients treated with infliximab within 2 years following a proactive therapeutic drug monitoring regimen. A modest benefit of adjunctive methotrexate in sustaining infliximab response was observed. Larger scale protocolised studies would help determine which patients may benefit from this approach.