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* = Presenting author

P390 To double dose or not to double dose? That is the question: Single centre experience in the use of infliximab antibodies and levels in a paediatric IBD (pIBD) cohort

B. Huggett*, S. Sider, S. Chadokufa, N. Acton, N. Shah, F. Kiparissi

Great Ormond Street Hospital, London, United Kingdom

Background

Biologic therapy with infliximab (INF) in paediatric inflammatory bowel disease (pIBD) is now standard treatment in patients who have failed thiopurines. Previous loss of clinical response pre-antibody and level availability usually led to switch in medical treatment. We now know that positive antibodies (AB) and low levels on biologic treatment are correlated with loss of clinical response. Aim: to evaluate monitoring of INF AB and levels and the efficacy of double dosing INF in patients with low levels with or without AB.

Methods

A retrospective study was performed on 23 patients: 22 on INF at 5mg/kg at 8 weekly intervals; 1 received 10 mg/kg at 6 weekly intervals because of loss of clinical response; 15 were Crohn’s disease; patients; 4 with ulcerative colitis; and 4 IBD unclassified (3 early onset IBD); male n = 16, median age of 12 years, with range of 3–16 years. Levels and antibodies were taken routinely, dose changed according to results, and repeat levels/AB were done with subsequent biologic treatment. Therapeutic range for INF was > 2.0 mg/L with negative AB < 10. INF doses were doubled to 10 mg/kg stat dose if levels were < 2.0 and/or AB were present.

Results

In total, 8 patients were excluded: 1 developed skin side effects; 3 patient’s treatment were stopped because of clinical remission; and 4 patients because of pending results. Further, 4/15 subjects with low INF levels and high antibodies (median 200, range 200–231 level, range < 0.1– < 0.8 with median of 0.2) were directly swapped to adalimumab. Moreover, 3/15 patients with low INF levels (median 1.4, range 0.8–1.7) but negative AB, had their dose increased to 10mg/kg, with therapeutic range (2.5–7.1) and ongoing negative AB. Of 4/15 patient who had low INF levels (3 had negative AB and 1 low level AB of 18), all received double doses, with levels remaining sub-therapeutic (median 1, range 0.3–1.2) and development of AB (median 25, range 18–45) in previous negative patients and further increase in antibodies. In addition, 3/4 of these patients are awaiting future treatment plans, and 1 was switched directly to adalimumab. Another 3/15 patients with low levels and negative AB (median 0.3, range 0.2–1.0) received double dose, and drug levels remained sub-therapeutic (median 1.6 range 0.8–1.7), currently awaiting future treatment plan following these results. Finally, 1/15 with sub-therapeutic levels and increasing antibodies (from 47 to 170) received 10mg/kg, which lead to decreased antibodies of 78; however, there was no clinical response, and adalimumab was commenced.

Conclusion

Our study suggests that INF treatment can be prolonged if specific AB and level patterns are present; however, doubling the dose might not lead to normal therapeutic ranges and/or have any clinical response. Performing INF drug levels and antibodies have improved patient outcomes and safety.