Abstract
Background
Vedolizumab (VDZ) is less effective in Inflammatory Bowel Disease (IBD) when used in anti-Tumor Necrosis Factor (TNF) failures as compared to anti-TNF naïve patients. However, the outcomes of sequencing anti-TNF after VDZ failure remain unknown. We report on the effectiveness and safety of anti-TNF as a second-line biologic after VDZ failure in pediatric IBD patients.
Methods
Data was collected as part of an ongoing pediatric IBD observational treatment registry and included demographics, disease behavior, location, disease activity (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) or partial Mayo score (pMS) for ulcerative colitis (UC) and IBD-unspecified (IBD-U)), adverse events, treatment and surgical history. Primary outcome was steroid-free clinical remission at last follow up. Secondary outcomes were CRP normalization and adverse events including infusion reactions, infections, hospitalizations, and IBD related surgeries. Descriptive statistics summarized the data (median [interquartile range (IQR)]) and univariate analyses tested associations.
Results
A total of 21 children and young adults (6 CD:14 UC:1 IBD-U; 19/21 colonic only disease) were treated with VDZ for a median [IQR] duration of 25 [11–59] weeks. VDZ was discontinued due to primary non-response (57%), secondary loss of response (38%), or an adverse event (5%). Nineteen (90%) patients were induced with infliximab (IFX), 1 with adalimumab, and 1 with golimumab and were followed for a median of 100 [35–148] weeks after anti-TNF induction (Table 1). Fifteen (71%) patients remained on anti-TNF therapy at last follow up for a median duration of 53 [34–112] weeks. All 15 patients achieved steroid-free clinical remission, and 9 (60%) patients also had a normal CRP (Figure 1). Remission rates were numerically higher in UC/IBD-U vs. CD (80% vs. 50% P = 0.27). All 6 (28%) patients (3 CD and 3 UC) who discontinued anti-TNF therapy after a median duration of 15 [7–24] weeks initially had a primary non-response to VDZ. Three patents had a primary non-response to anti-TNF, 2 had a secondary loss of response, and 1 had an anaphylactic infusion reaction. No serious adverse events, hospitalizations or serious infections attributable to anti-TNF therapy occurred.
Conclusions
Our results suggest that anti-TNF therapy is efficacious and safe after primary failure with VDZ in pediatric IBD patients and this was particularly so in patients with colonic disease location, regardless of IBD classification.
Effect of vedolizumab dose intensification on serum drug concentrations and regain of response in inflammatory bowel disease patients with secondary loss of response
