Immunomodulators provide no reduction in loss of response for inflammatory bowel disease patients starting anti-TNF-alpha therapy.

Abstract

Aims: In Inflammatory Bowel Disease (IBD), large registration studies have not shown a significant difference in clinical endpoints in patients treated with anti-tumour necrosis factor alpha (anti-TNF) monoclonal antibody alone versus with immunomodulator co-therapy, however from recent data, there is a trend towards co-therapy to reduce immunogenicity to anti-TNFs. Given the risks of immunomodulators, particularly thiopurines, we queried the long-term therapeutic benefits of immunomodulator co-therapy. Our aim was to assess whether anti-TNF monotherapy was associated with earlier loss of response (LOR) in patients with Inflammatory Bowel Disease (IBD) versus combination therapy in a real world cohort. Method(s): A retrospective audit was conducted of all patients with IBD receiving anti-TNF therapy in a tertiary centre. All patients on anti-TNF therapy with an accurate date for TNF commencement and adequate correspondence to determine end-points were included. Patients with prior exposure to any anti-TNF agent were excluded. Outcomes measured included weight and body mass indices pre and post anti-TNF and days to first loss of response; defined by an admission or surgery post-induction, escalation of TNF dose or concurrent immunomodulators for clinical LOR, emergence of a new fistula or rising Crohn's Disease Activity Index > 150 (CDAI). Statistical analysis was performed with GraphPad Prism v6. Result(s): A total of 94 patients were included for analysis; 53 induced with Infliximab (IFX) and 41 induced with Adalimumab (ADA). 91 patients were treated for Crohn's Disease and 3 patients treated for Ulcerative Colitis. 81 patients received co-therapy and 13 patients received monotherapy. 42 (45%) patients had loss of response during follow-up; 23 (55%) IFX patients and 19 (45%) ADA patients (p = ns). Causes for LOR included hospital admission (n = 13, 31%), clinical LOR (n = 21, 50%), surgery (n = 6, 14%) or new fistula (n = 2, 5%). The median time to loss of response in patients with concomitant immunomodulator therapy was 1027 days, compared to 980 days in patients treated with anti-TNF monotherapy. (p = 0.78) (Figure 1) There was no difference between the type of immunomodulator co-therapy and time to loss of response. There was no correlation between baseline CDAI or body mass index and time to loss of response. Baseline haemoglobin, albumin and C-reactive protein were no different between those who experienced loss of response and those who did not. No difference was found in the type of anti-TNF agent used and time to loss of response. (Figure Presented) Conclusion(s): In this Australian ambulatory specialist care setting, patients treated with anti-TNF therapy had similar rates of loss of response and outcomes, regardless of immunomodulator use, at both short-term and extended follow-up.