Anti-ADA antibody reversal in IBD

May 23, 2017 - E-Mentoring in IBD | Volume 10 • 2017

Issue 10

Clinical Question

For patients with IBD who develop anti-adalimumab antibodies (AAA) and lose response to adalimumab mono therapy, is there a way to reverse immunogenicity and restore therapeutic effectiveness?

Editor’s Bottom Line

Yes. Follow loss of response on adalimumab monotherapy optimization with combination immunosuppressive therapy to reverse antibodies, raise trough levels and regain clinical response in ~50% of patients.

Editorial Note

While this study is small, it does replicate real world clinical experience. With loss of clinical response the confirmation of active disease followed by optimization of therapy is best practice.


Ungar B, Kopylov U, Engel T, et al. Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab. Aliment Pharmacol Ther. 2017 Jan;45(2):276–82.


Between 2012 and 2016, medical charts of patients receiving adalimumab (ADA) monotherapy for IBD were reviewed. As part of usual care, patients were tested for ADA and AAA trough levels after a clinical loss of response, defined as Harvey Bradshaw Index ≥5 and Crohn’s disease activity index >150 for Crohn’s disease (CD) or simple clinical colitis activity Index >3 for ulcerative colitis (UC). Patients had to test positive for AAA on two consecutive occasions prior to the optimization (i.e., rescue) with combination immunomodulatory therapy listed below:

  • Weekly methotrexate, 15–25 mg subcutaneously or 10–15 mg orally, or
  • Daily azathioprine, 2–2.5 mg/kg orally, or
  • Daily mercaptopurine, 1–2 mg/kg orally

The outcomes sought were to eliminate AAA and elevated ADA levels, and regain clinical response.

The cohort comprised 21 patients with CD and 2 with UC. A total of 9 received methotrexate while 14 received purine therapy. Combination ADA-immunomodulator therapy led to sero-reversal in 11 (50%) of patients after a median time of 20 weeks (interquartile range 12–26 weeks). These patients also had increases in drug trough levels and restored clinical response to ADA therapy. Inflammatory markers were normalized for 9 patients. The remaining 12 patients did not regain response to ADA and continued to produce AAAs. No predictors were found that could identify patients who respond to this type of salvage therapy.


Study Design: Retrospective observational study
Funding: Chaim Sheba Medical Center, Rambam Health Care Center, and Leona M. and Harry B. Helmsley Charitable Trust
Allocation: n/a
Setting: Tertiary care settings in France and Israel
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.