P0653 Switching from intravenous to subcutaneous infliximab maintains higher trough levels, with reduction or disappearance of antidrug antibodies and allows de-escalation of concomitant immunomodulators, independent of HLA DQA1*05 status: a prospective study

Abstract Background Switch of Infliximab from intravenous (IV) to subcutaneous (SC) route in inflammatory bowel disease is reported to produce higher drug levels but impact on (ADAs) is not known. Furthermore, the impact of cessation of concomitant immunomodulators (IMMs) following switch on trough levels or development of ADAs is also not evaluated so far. We aimed to study the impact of cessation of IMMs following switch of infliximab from IV to SC route on ADAs status and determine relationship with HLA-DQA1*05 status. Methods Consecutive patients who participated in a planned switch programme were prospectively included. HLA status was determined at initiation of Infliximab as part of standard screening in our unit. Clinical, biomarker and pharmacokinetic data were collected pre-switch, and at 8 weekly intervals post switch. Trough levels and ADAs status in patients who discontinued or reduced the dose of IMMs were compared with those who remained or continued same dose on IMMs. We also evaluated the impact of HLA status on development of ADAs post switch. Results A total of 274 patients (M: F = 1.1:1), Median age at diagnosis 33 years (2-76), UC/CD (123/151) who completed at least 8 weeks follow up were included. Median duration of follow up was 28 weeks. 124 patients (45.3%) were on concomitant IMMs and 107 (40.4%) was HLADQA1*05 positive. The mean infliximab trough level prior to switch was 7.30 µg/mL which increased 8 weeks post switch to 15.05 µg/mL (p < 0.001). The enhancement of levels persisted at 40 weeks (15.74 µg/mL) and at week 90 (15.26 µg/mL). 74 patients (27%) were positive for ADAs before switch; in 16 patients (22%) the ADAs disappeared at 8 weeks and in further 8 (total 33%) by 40 weeks. In total antibody titre reduced or become negative in 47 patients (63.5%), static in 6 patients (8.1%) but increased in 21 patients (28.4%); only 3 had significant neutralizing antibodies with low trough levels. 28 of the 124 patients (23%) had IMMs discontinued, and dose reduced in further 8 patients. The overall de-escalation rate was 29%, and HLA did not significantly impact trough levels or ADA development. Eleven patients (4.0%) switched back to IV due to personal preference and 2 (0.7%) were switched out of class due to secondary loss of response. Drug persistence with SC switch was 95.3%. Conclusion Switch from IV to SC infliximab is effective in maintaining and enhancing trough levels with positive impact on reducing ADAs and in some cases lead to disappearance of anti-drug antibodies. It is feasible to de-escalate concomitant IMMs in a considerable proportion of patients following switch irrespective of the HLA status. This data needs confirmation from the ongoing randomised controlled trial MINIMISE (ISRCTN95420128) Conflict of interest: Dr. Al-Dujaily, Hashem: No conflict of interest Fitzgerald, Abbie-Lei: No conflict of interest Mcbride, Jodie: No conflict of interest Robertson, Hayley: No conflict of interest Talbot, Alison: No conflict of interest Messiha, Maged: No conflict of interest Thomas, Mithun: No conflict of interest Whitehead, Emma: No conflict of interest Sebastian, Shaji: Grant: Takeda, Tillots pharma, Biogen, Pfizer, Abbvie, Johnson & Johnson, Olympus -Odin Vision Personal Fees: Tillots, Johnson & Johnson, Olympus Odin Vision, AbbVie, Takeda, Merck, Pharmacosmos, Amgen, Eli Lilly, BMS, Odin Vision Non-financial Support: Tillots, Takeda, AbbVie, Celltrion, Johnson & Johnson, Eli Lilly, Alphasigma, Ferring Pharma