Faculty Collaboration Database

Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab. Clin Gastroenterol Hepatol 2023 Oct;21(11):2908-2917.e10

Date

10/25/2022

Pubmed ID

36280102

DOI

10.1016/j.cgh.2022.10.016

Scopus ID

2-s2.0-85147031581 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

BACKGROUND AND AIMS: The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics.

METHODS: This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs).

RESULTS: A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 10⁸ red blood cells (RBCs), and those receiving combination therapy with thiopurine or oral methotrexate had significantly higher infliximab concentrations when compared with monotherapy (median levels of 17.4 μg/mL on thiopurine with 6-TGN ≥146 pmol per 8 × 10⁸ RBCs, 17.1 on methotrexate, and 3.9 on infliximab monotherapy; P = .001 for both comparisons). However, there was no association between the use of immunomodulators and 6-TGN concentrations with vedolizumab (median levels of 8.8 on thiopurine with 6-TGN ≥152 pmol per 8 × 10⁸ RBCs, 6.8 on methotrexate, and 10.5 on vedolizumab monotherapy; P > .05 for both comparisons) or ustekinumab median concentrations (median levels of 5.0 on thiopurine with 6-TGN ≥154 pmol per 8 × 10⁸ RBCs, 5.2 on methotrexate and 7.0 on ustekinumab monotherapy; P > .05 for both comparisons). Fourteen (12%) patients had anti-infliximab antibodies, while 1 patient had ADAs in each of the other drug cohorts.

CONCLUSIONS: Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.

Author List

Yarur AJ, McGovern D, Abreu MT, Cheifetz A, Papamichail K, Deepak P, Bruss A, Beniwal-Patel P, Dubinsky M, Targan SR, Melmed GY

Author

Poonam Beniwal-Patel MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal, Humanized
Azathioprine
Humans
Immunologic Factors
Immunosuppressive Agents
Inflammatory Bowel Diseases
Infliximab
Mercaptopurine
Methotrexate
Prospective Studies
Ustekinumab