. 2023 Jun;68(6):2604-2623.

doi: 10.1007/s10620-023-07837-0. Epub 2023 Feb 20.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature

Elliot M Berinstein¹, Jessica L Sheehan^{2

3}, Janson Jacob⁴, Calen A Steiner⁵, Ryan W Stidham^{2

6}, Carol Shannon⁷, Shrinivas Bishu², Jake Levine⁴, Shirley A Cohen-Mekelburg^{2

3

8}, Akbar K Waljee^{2

3

8

9}, Peter D R Higgins^#², Jeffrey A Berinstein^#^{10

11}

Affiliations

¹ Department of Medicine, Trinity Health Ann Arbor Hospital, Ypsilanti, MI, USA.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
³ Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA.
⁵ Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁷ Taubman Health Sciences Library, University of Michigan, Ann Arbor, MI, USA.
⁸ VA Center for Clinical Management Research, VA Ann Arbor Health Care System, Ann Arbor, MI, USA.
⁹ Department of Learning Health Sciences, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA. jberinst@med.umich.edu.
¹¹ Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA. jberinst@med.umich.edu.

^# Contributed equally.

PMID: 36807832
PMCID: PMC9942632
DOI: 10.1007/s10620-023-07837-0

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature

Elliot M Berinstein et al. Dig Dis Sci. 2023 Jun.

. 2023 Jun;68(6):2604-2623.

doi: 10.1007/s10620-023-07837-0. Epub 2023 Feb 20.

Authors

Affiliations

¹ Department of Medicine, Trinity Health Ann Arbor Hospital, Ypsilanti, MI, USA.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
³ Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA.
⁵ Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁷ Taubman Health Sciences Library, University of Michigan, Ann Arbor, MI, USA.
⁸ VA Center for Clinical Management Research, VA Ann Arbor Health Care System, Ann Arbor, MI, USA.
⁹ Department of Learning Health Sciences, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA. jberinst@med.umich.edu.
¹¹ Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA. jberinst@med.umich.edu.

^# Contributed equally.

PMID: 36807832
PMCID: PMC9942632
DOI: 10.1007/s10620-023-07837-0

Erratum in

Correction to: Efficacy and Safety of Dual Targeted Therapy for Partially or Non‑responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.
Berinstein EM, Sheehan JL, Jacob J, Steiner CA, Stidham RW, Shannon C, Bishu S, Levine J, Cohen-Mekelburg SA, Waljee AK, Higgins PDR, Berinstein JA. Berinstein EM, et al. Dig Dis Sci. 2023 Dec;68(12):4540. doi: 10.1007/s10620-023-08130-w. Dig Dis Sci. 2023. PMID: 37891442 Free PMC article. No abstract available.

Abstract

Background: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD.

Methods: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021.

Results: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib.

Conclusion: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

Keywords: Biologics; Combination therapy; Inflammatory bowel disease; Therapeutics.

PubMed Disclaimer

Conflict of interest statement

PDRH received consulting fees from AbbVie, Amgen, Genentech, and Pfizer. RWS received consulting fees from AbbVie, Janssen, Takeda, Merck, Gilead, Eli Lily, Exact Science, Evergreen Pharmaceuticals, Corrona LLC. JAB received consulting fees from BUHLMANN Diagnostics Corp. All other authors report no relevant disclosures.

Figures

**Fig. 1**
Included and excluded studies

See this image and copyright information in PMC

References

1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066–2078. doi: 10.1056/NEJMra0804647. - DOI - PMC - PubMed
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1. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141(4):1194–1201. doi: 10.1053/j.gastro.2011.06.054. - DOI - PubMed
1. Peyrin-Biroulet L, Lémann M. Review article: remission rates achievable by current therapies for inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33(8):870–879. doi: 10.1111/j.1365-2036.2011.04599.x. - DOI - PubMed
1. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383–1395. doi: 10.1056/NEJMoa0904492. - DOI - PubMed

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Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature

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Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature

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Erratum in

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