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Rheumatology Fellow, Division of Rheumatology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Clinical Assistant Professor, Division of Rheumatology, Faculty of Medicine, University of British Columbia; Director of Clinical Trials, Arthritis Research Centre of Canada, Vancouver
Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, University of British Columbia; PhD Candidate, Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia
PhD Candidate, Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia
Associate Professor, Department of Health Care and Epidemiology, University of British Columbia
Reprints: Carlo A Marra BSc(Pharm) PharmD FCSHP, Centre for Health Evaluation and Outcome Sciences, 620B-1081 Burrard St., St. Paulís Hospital, Vancouver, British Columbia V6Z 1Y6, Canada, FAX 604/806-8778, cmarra{at}interchange.ubc.ca
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and pharmacoeconomic impact of infliximab in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA).
DATA SOURCES: MEDLINE and Pre-MEDLINE (1966–June 2002) and manufacturer prescribing literature were employed to find English-language articles on infliximab. Additional studies and abstracts were identified from the bibliographies of reviewed literature and conference proceedings.
STUDY SELECTION/DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Safety data were extracted from clinical trials and postmarketing surveillance. Priority was given to randomized, double-blind, placebo-controlled studies for the assessment of efficacy. All available economic evaluations were included.
DATA SYNTHESIS: Infliximab is a new monoclonal antibody
that appears to work by a unique mechanism: inhibiting the action of tumor
necrosis factor-
(TNF-). Infliximab is administered by
intravenous infusion. In clinical trials in CD, infliximab significantly
decreased the CD activity index compared with placebo in treatment-resistant
disease and significantly reduced the number of draining fistulas in
fistulizing disease. In RA, when infliximab was added to methotrexate (MTX),
it resulted in a significant improvement in most disease outcome measures when
compared with MTX plus placebo. Few major adverse effects were reported in the
clinical trials; however, serious adverse events, including malignancy and
demyelination, have been reported in postmarketing surveillance. Also,
increased susceptibility to infections (including tuberculosis) has been
reported.
CONCLUSIONS: Infliximab is an effective new agent for the
treatment of CD and RA. Its apparent unique mechanism of action makes
infliximab an important addition to therapy. Caution should be exercised when
considering infliximab for individuals who have chronic or recurrent
infections, mild congestive heart failure (New York Heart Association [NYHA]
class I/II), nervous system disorders, or live or have lived in an area
endemic for histoplasmosis. Infliximab is contraindicated for patients with a
clinically important, active infection, moderate to severe congestive heart
failure (NYHA class III/IV), or an allergy to mouse proteins or any of the
ingredients in infliximab. Further long-term efficacy, safety, and economic
data on infliximab are required. Also, for the treatment of RA, the burden of
administering infliximab (as a 2-hour supervised infusion) has to be
considered when choosing among anti-TNF- medication (as the other 2
approved agents, etanercept and adalimumab, can be self-administered by
subcutaneous injection).
Key Words: Crohn's disease, infliximab, rheumatoid arthritis, tumor necrosis factor-
Published Online, July 10, 2003. www.theannals.com, DOI 10.1345/aph.1C039
THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE
UNIVERSAL PROGRAM NUMBER: 407-000-03-024-H01
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