Real World Experience in Therapeutic Drug Monitoring in Inflammatory Bowel Disease: Lack of Anti-Drug Antibodies to Vedolizumab and Ustekinumab Compared to Anti-TNF Agents in IBD

Abstract

Introduction: Background: Current evidence supports the use of reactive therapeutic drug monitoring (TDM) to guide treatment changes in inflammatory bowel disease (IBD) patients treated with anti-TNF agents. However, there is less data available on drug monitoring in other classes of biologics. Optimal management strategies are needed for patients with development of drug antibodies. Aims: To assess the frequency of drug antibody formation during reactive drug monitoring, as well as subsequent management strategies. Methods: TDM was obtained from 341 patients seen at our IBD center due to ongoing clinical symptoms and/or endoscopic, biologic markers (fecal calprotectin, ESR, CRP), or radiologic studies suggestive of active disease. Drug levels were drawn at trough between May 2017 and June 2018 on patients taking any of the 6 biologic medications: adalimumab, infliximab, certolizumab, golimumab, ustekinumab, and vedolizumab. Results: This patient population included 29% ulcerative colitis (UC), 70% Crohn's disease, and 1% IBD-indeterminate with 60% being female, and 83% Caucasian (Table 1). In total, 10/341 (2.9%) had antidrug antibodies (ADA) ranging from 5 to greater than 160. Of these, 80% had undetectable drug levels with high level ADA, while the remaining 20% had low level ADA, and detectable drug levels ranging from 1.5 to 34.3. Of those with ADA, 90% had Crohn's disease and 10% had UC. Six out of 341 (1.7%) had undetectable drug levels, but had not developed drug antibodies. Of patients with drug antibodies, 30% were to adalimumab, 30% infliximab, 30% certolizumab, 10% golimumab, but none were seen with ustekinumab or vedolizumab (Chart 1). Of the ten patients with antibody formation, 90% were switched to a different biologic medication. 40% were switched to another anti-TNF while 50% were switched to a different drug class. In one patient with detectable drug level but antibody formation to golimumab, re-induction was attempted, however the patient ended up undergoing colectomy for refractory ulcerative colitis. After switch in biologic therapy, 75% of those with follow up were found to be in clinical remission. Conclusion: Drug antibodies appear to be uncommon in vedolizumab and ustekinumab compared to anti-TNF agents. Reactive TDM was helpful in our patient population decision making as the majority of patients who developed drug antibodies achieved clinical remission after switch to an alternative biologic.600_A Figure 1. Demographics of Patients with Inflammatory Bowel Disease Undergoing Therapeutic Drug Monitoring600_B Figure 2. Drug and Anti-drug Antibody Levels in Inflammatory Bowel Disease Patients Undergoing Therapeutic Drug Monitoring