THE IMPACT OF INTERMEDIATE TITER ANTIBODIES TO ADALIMUMAB (ATA) AND INFLIXIMAB (ATI) ON CLINICAL OUTCOMES IN PATIENTS WITH CROHN’S DISEASE (CD) OR ULCERATIVE COLITIS (UC)
Authors: Wang Chaoyang , Tolaymat Mazen , Cross Raymond 
Published: January 2021

Abstract

Background
Anti-TNF drugs, adalimumab (ADA) and infliximab (IFX), are effective treatments for ulcerative colitis (UC) and Crohn’s disease (CD). However, 30% of patients do not respond to treatment (primary non-response) and 40% lose response over time (loss of response). Loss of response is often due to development of antibodies to ADA (ATA) and IFX (ATI). While it is known that undetectable or low ATA/ATI titers (&lt;200 ng/mL) are associated with better outcomes and high ATA/ATI titers (&gt;1000 ng/mL) are associated with poor outcomes, the significance of intermediate ATA/ATI titers (200–999 ng/mL) is not well understood. This study aims to investigate the impact of intermediate ATA/ATI titers on outcomes in CD and UC patients.

Methods
A retrospective chart review was conducted on CD and UC patients to determine associations between intermediate ATA/ATI titers and adverse clinical outcomes. The primary clinical outcome of interest is persistence on anti-TNF therapy 1 year after measurement of ATA/ATI titers. Secondary clinical outcomes of interest include clinical response to therapy 1 year after measurement of ATA/ATI titers. Participants consist of UC or CD patients treated with IFX or ADA at the University of Maryland IBD Program between October 2016 and October 2019 that had at least one measurement of ADA/ IFX and ATA/ATI during the study period.

Results
376 patients were identified (ADA=157 and IFX=219). 271 of 322 low titer patients persisted on their original anti-TNF compared to 9 of 15 intermediate titer patients (p=0.026) and 1 of 10 high titer patients (p&lt;0.0001) (Table 1). The odds ratio (OR) of persistence comparing intermediate titer to low was 0.26 (0.09 to 0.80) and comparing high titer to low was 0.02 (0.00 to 0.14). In the low titer group, 47, 33, and 251 of 331 patients had no, partial, or complete response to therapy, respectively. In the intermediate titer group: 6, 1, and 8 of 15 patients, had no, partial or complete response; in the high titer group: 3, 1, and 3 of 10 patients, had no, partial, or complete response (Table 2). The difference in distribution of patients who showed no, partial, and complete response was significantly different between low titer patients and intermediate titer patients (p=0.019), but not different between intermediate titer and high titer patients (p=0.440).

Conclusion
Patients with intermediate titers were more likely than patients with low titers to lose response to anti-TNF and require a change anti-TNF therapy. Although our sample size of patients with intermediate titers was small, providers should consider dose optimization of anti-TNF with or without addition of an immune suppressant when intermediate titers are present. An alternative approach would be to repeat drug and antidrug antibody levels to assess for worsening pharmacokinetics.

Persistence on original anti-TNF 1 year after first measurement in low, intermediate, and high titer patients (Fisher’s test).

Response to therapy 1 year after first measurement in low, intermediate, and high titer patients (Fisher’s test).