Infliximab in clinical routine: experience with Crohn's disease and biomarkers of inflammation over 5 years.
BACKGROUND
Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab.


OBJECTIVE
To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA).


METHODS
During 1999-2008, CD patients were monitored for disease activity by Harvey-Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies.


RESULTS
A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey-Bradshaw index decreased with infusions during the first year of treatment (P < 0.0001), whereas hemoglobin (P < 0.01) and albumin (P <0.001) increased, C-reactive protein (P < 0.01) decreased, platelets (P <0.001) increased, and leukocytes (P< 0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P < 0.0001), and nitrite (P < 0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found.


CONCLUSIONS
Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
Lönnkvist
Maria H
MH
Department of Medicine, Gastroenterology and Hepatology Unit, Karolinska Institutet, Stockholm, Sweden.
Befrits
Ragnar
R
Lundberg
Jon O
JO
Lundahl
Joachim
J
Fagerberg
Ulrika L
UL
Hjortswang
Henrik
H
van Hage
Marianne
M
Hellström
Per M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000097:blood; D011594:Psychometrics; D011788:Quality of Life; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab