Trough s-infliximab and antibodies towards infliximab in a cohort of 79 IBD patients with maintenance infliximab treatment.
OBJECTIVE
The anti-TNF antibody infliximab is effective in inducing remission in Crohn's disease as well as in ulcerative colitis and many patients are treated for several years with sustained clinical remission. However, the role of monitoring s-infliximab and antibodies towards infliximab during maintenance treatment remains unclear. Our aim was to correlate serum drug levels and antibodies to clinical activity, CRP, albumin and concomitant immunosuppression in a cohort on maintenance infliximab treatment.


METHODS
We included 79 patients with Crohn's disease or ulcerative colitis who had responded to infliximab and received maintenance treatment (4-69 infusions) in this retrospective study. Infliximab levels and antibodies towards the drug were analyzed with in-house-developed ELISA assays.


RESULTS
The mean s-infliximab was significantly higher in patients in remission (4.1μg/mL) as compared with disease flare (mean 1.8μg/mL); p<0.001. The s-infliximab showed a significant negative correlation with Harvey-Bradshaw index (r=-0.21; p<0.05). Serum-infliximab progressively decreased with the number of accumulated infusions (p<0.05). In patients with undetectable trough levels, 55% of the patients with concomitant immunosuppressive were positive for antibodies against infliximab, as compared with 94% of patients on monotherapy. Patients with undetectable serum-infliximab were in clinical remission at 25% of the visits.


CONCLUSIONS
The trough level 4.1μg/mL may serve as cut-off for clinical remission. Drug trough levels decreased during treatment and almost all patients with undetectable s-infliximab and monotherapy had developed antibodies against the drug.
Dept of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Per
P
Marits
Dept of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Laura
L
Landucci
Dept of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Ulf
U
Sundin
Dept of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Loa
L
Davidsdottir
Dept of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Jakob
J
Nilsson
Dept of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Ragnar
R
Befrits
Dept of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Ann-Charlotte
AC
Wikström
Dept of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Dept of Gastroenterology and Hepatology, Karolinska University Hospital and Dept of Clinical Science and Education, karolinska Institutet, Stockholm, Sweden. Electronic address: Michael.eberhardson@karolinska.se.
Michael
M
Eberhardson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
Antibodies towards infliximab;; Crohn's disease;; Drug monitoring; Serum-infliximab;; Trough levels;; Ulcerative colitis;