Introduction

Several biologic therapies are available for the treatment of Inflammatory Bowel Diseases (IBD). Anti-TNF agents have been, and continue to be, frequently used as first-line agents. Choice of a second biologic after failure of a first anti-TNF remains a common clinical scenario with limited data available to guide choice. Mode of failure for the first-line anti-TNF, classed as primary non-response (PNR) or secondary loss of response (LOR) has been suggested as a means of guiding treatment choice.

Aims & Methods

To compare the efficacy of second line biologic therapies [infliximab (IFX), adalimumab (ADA), golimumab (GLM), vedolizumab (VDZ), ustekinumab (UST)] in patients with Ulcerative Colitis (UC) and Crohn’s Disease (CD) enrolled in the UK IBD BioResource, after first line anti-TNF failure.Demographic, disease, treatment and outcome data were retrieved. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. Effectiveness of treatment was based on persistence free of treatment discontinuation or treatment failure. Failure was defined as occurring if any of the following occurred: (a) clinician-recorded treatment failure (b) start of treatment with a different biologic drug (c) occurrence of resectional or defunctioning bowel surgery. We compared Kaplan Meier curves for treatment failure-free survival after IPTW and used a log rank test for differences between the groups.To testwhether the mode of first line treatment failure affected different second-line treatments’ efficacies, we classified first anti-TNF failure as PNR or non-PNR (an approximation for LOR) for subgroup analyses.

Results

For patients with UC, we analysed efficacy after ADA (n=301) and IFX failure (n=519) separately due to differences in outcomes between these drugs when used in first-line therapy in the same cohort. Second line VDZ demonstrated superior outcomes up to the three year follow up, compared to second line IFX after ADA failure (p<0.01) and compared to second line ADA after IFX failure (p<0.001). After PNR to IFX, VDZ had a significantly better treatment survival free of discontinuation or failure compared to ADA (p = 0.002) whereas in the case of PNR to ADA, there were no significant differences between those who received second line VDZ and IFX. For NPNR after both IFX or ADA, VDZ therapy had significantly better efficacy than ADA or IFX respectively (p < 0.001).
For patients with CD, we combined first-line ADA and IFX cohorts due to similar outcomes observed when used in first-line therapy in the same cohort. Patients who experienced anti-TNF failure had significant better outcomes when treated with a second line non-anti-TNF biologic (UST or VDZ, n=614) than those who received a second line anti-TNF (n=1976, p=0.007). In the case of PNR, we found no difference between second line anti-TNF vs non-anti-TNF biologics. However, after NPNR to anti-TNF, there was a significantly better performance for non-anti-TNF compared to anti-TNF biologics (p=0.01).

Conclusion

In the common scenario of first line anti-TNF therapy failure switching out of class seems to offer better outcomes after anti-TNF failure both in UC and CD. In contrast to some algorithms, after NPNR to anti-TNF agents, a switch out-of-class to a non anti-TNF therapy afforded better outcomes in both UC and CD compared to switching within the class of anti-TNF agents.