Loss of Infliximab Into Feces Is Associated With Lack of Response to Therapy in Patients With Severe Ulcerative Colitis.
OBJECTIVE
It is not clear why some patients with ulcerative colitis (UC) do not respond to treatment with anti-tumor necrosis factor (TNF) agents, such as infliximab. It could be that some patients have high level of inflammation, with large quantities of TNF to be neutralized by the drug. We investigated whether loss of anti-TNF agents through ulcerated intestinal mucosa reduces the efficacy of these drugs in patients with severe UC.


METHODS
We collected fecal samples from 30 consecutive patients with moderate to severely active UC during the first 2 weeks of infliximab therapy at the University of Amsterdam hospital. Infliximab concentrations were measured in serum and supernatants of fecal samples using an enzyme-linked immunosorbent assay (Sanquin Biologicals Laboratory, Amsterdam, The Netherlands). Clinical and endoscopic responses were assessed 2 and 8 weeks and 3 months after treatment began.


RESULTS
Infliximab was detected in 129 of 195 fecal samples (66%); the highest concentrations were measured in the first days after the first infusion. Patients that were clinical nonresponders at week 2 had significantly higher fecal concentrations of infliximab after the first day of treatment than patients with clinical responses (median concentration, 5.01 μg/mL in nonresponders vs 0.54 μg/mL in responders; P = .0047). We did not observe a correlation between fecal and serum concentrations of infliximab.


CONCLUSIONS
Infliximab is lost into stools of patients with UC. High fecal concentrations of infliximab in the first days after therapy begins are associated with primary nonresponse. Additional studies are needed to determine how therapeutic antibodies are lost through the intestinal mucosa and how this process affects treatment response. Clinical trial ID: NL41310.018.12.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
Johannan F
JF
Brandse
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
Gijs R
GR
van den Brink
Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
Manon E
ME
Wildenberg
Biologicals Laboratory, Sanquin Laboratory, Amsterdam, The Netherlands.
Desiree
D
van der Kleij
Sanquin Research, Sanquin Laboratory, Amsterdam, The Netherlands.
Theo
T
Rispens
Department of Gastroenterology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
Jeroen M
JM
Jansen
Department of Hospital Pharmacy, Academic Medical Center, Amsterdam, The Netherlands.
Ron A
RA
Mathôt
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Cyriel Y
CY
Ponsioen
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Mark
M
Löwenberg
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: g.dhaens@amc.uva.nl.
Geert R A M
GR
D'Haens
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016903:Drug Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
IBD; Inflammatory Bowel Disease; Intestinal Loss of Protein; Monoclonal Antibody Therapy