ABSTRACT
BACKGROUND: Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited. METHODS: We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded. RESULTS: Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn's disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range [1.1-4.3]) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels <5 µg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten (7%) patients (9 Crohn's disease, 1 ulcerative colitis) underwent bowel resections after beginning infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007). CONCLUSIONS: ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease.
Subject(s)
Antibodies, Monoclonal/blood , Antibodies/blood , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Adolescent , Adult , Antibodies, Monoclonal/therapeutic use , Case-Control Studies , Child , Child, Preschool , Colitis, Ulcerative/blood , Colitis, Ulcerative/immunology , Crohn Disease/blood , Crohn Disease/immunology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Infliximab , Male , Prognosis , Young AdultABSTRACT
Animal-extracted injectable hyaluronidases have been used safely for more than 50 years to increase the dispersion and absorption of coadministered drugs and fluids; however, concern still exists about the allergic and immunological risks of these products. Hylenex recombinant, a novel formulation of recombinant human hyaluronidase, has been developed as an alternative to these animal-derived hyaluronidases. Because recombinant human hyaluronidase is a human (nonforeign) protein manufactured into a purer preparation than the animal extracts, it is expected to convey reduced allergic and immunologic risks. The recombinant human hyaluronidase product was well tolerated in this double-blind, placebo-controlled, single-dose study. No allergic reactions were observed among the 100 volunteer subjects who were injected intradermally. These findings supported the US Food and Drug Administration approval of the recombinant human hyaluronidase product.
