PWE-050 Anti-drug antibodies to anti-TNFS: experience and outcomes at a tertiary IBD centre. (8th June 2018)

• Record Type: Journal Article
• Authors: Sebepos-Rogers, Gregory; Jayasooriya, Nishani; Gadhok, Radha; Gordon, Hannah; O'Donnell, Sarah
• Is Part Of: Gut. Volume 67(2018)Supplement 1
• Page Start: A92
• Page End: A93
• Publication Date: 2018-06-08
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2018-BSGAbstracts.182
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: Therapeutic drug monitoring in the setting of secondary loss of response to anti-TNF therapies has become a routine part of clinical practice in IBD. Decision making following the detection of anti-drug antibodies (ADAs) to Infliximab and Adalimumab remains variable, especially when further therapeutic options are limited and antibody levels are low. Methods: We retrospectively identified all patients with detectable ADAs to Infliximab or Adalimumab between 2014 and 2016 at a tertiary care adult IBD centre, using a drug sensitive assay. Follow-up was to end-2017 evaluating the therapeutic changes made on detection of antibodies, and the clinical outcomes thereafter. Results: 21 of 203 (10%) and 38 of 203 (19%) tested patients developed ADAs at a median interval of 12 and 8 months after starting therapy with levels above the reported range in 52% (>160 ng/mL) and 50% (>200 ng/mL) of Adalimumab and Infliximab patients respectively. The majority of testing was for suspected loss of response (46%) and partial response (15%). In contrast fewer were for post-induction (10%) and yearly reassessment (15%), of whom 80% had documented inactive disease. 17% had experienced an infusion reaction around the time of testing. For Adalimumab patients (figure 1), 4 had prior ADA to Infliximab. 71% had a co-prescribed immunomodulator (IM). The mean time from treatment initiation to ADA detection was 23 months. After ADA detection, 8 (38%) had their Adalimumab therapy continued. Of these, 5 (62%) had dose escalation, of whom 2 had successful ADA suppression and durable remission of 15 and 23 months after initial ADA detection (drug level 1.1 and 4.7 ug/mL respectively). The remaining 3 had persistent ADA at next testing. Of the 19 who discontinued Adalimumab, 32% required a third line out of class biologic. For Infliximab patients (figure 2), 61% had a co-prescribed IM. The mean time from treatment initiation to ADA detection was 17 months. After ADA detection, 9 (24%) continued on Infliximab. Of these, 5 had successful ADA suppression and sustained remission of 14–27 months to the end of the study (drug levels 2.9–9.6 ug/mL). Of the 33 who had a switch in class of biologic, 52% achieved remission. However, 9% subsequently required a third line and 6% a fourth line out of class biologic. For both groups, neither a high or low level of ADA, nor duration of biologic pre-testing were predictive of outcome. Conclusions: Our study shows some of the challenges in therapeutic drug monitoring when LOR is suspected. When ADAs were detected, most patients required a biologic switch in or out of class, and/or surgery, in line with consensus algorithms. However, it appears that in some cases a durable ADA suppression following dose escalation is possible and should be considered when there are limited other therapeutic options.