NIVELOIREIDEN HOITO SYTOKIINEJA HEIKENTÄMÄLLÄ

[Bb]

Lähettäjä: Soijuv Lähetetty: 5.6.2006 22:34

Tuumorinekroositekijöillä on merkittävä asema immuunijärjestelmässä. Reumaoireiden hoitoon toisinaan käytettävässä hoidossa heikennetään TNF:ää. Tästä on seurauksena suurentunut alttius sairastua infektioihin ja pahanlaatuisiin kasvaimiin.


Vol. 295 No. 19, May 17, 2006

Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious
Infections and Malignancies
Systematic Review and Meta-analysis of Rare Harmful Effects in Randomized
Controlled Trials

Tim Bongartz, MD; Alex J. Sutton, PhD; Michael J. Sweeting, MSc; Iain
Buchan, MD, MFPH; Eric L. Matteson, MD, MPH; Victor Montori, MD, MSc

JAMA. 2006;295:2275-2285.

Context Tumor necrosis factor (TNF) plays an important role in host defense
and tumor growth control. Therefore, anti-TNF antibody therapies may
increase the risk of serious infections and malignancies.

Objective To assess the extent to which anti-TNF antibody therapies may
increase the risk of serious infections and malignancies in patients with
rheumatoid arthritis by performing a meta-analysis to derive estimates of
sparse harmful events occurring in randomized trials of anti-TNF therapy.

Data Sources A systematic literature search of EMBASE, MEDLINE, Cochrane
Library, and electronic abstract databases of the annual scientific meetings
of both the European League Against Rheumatism and the American College of
Rheumatology was conducted through December 2005. This search was
complemented with interviews of the manufacturers of the 2 licensed anti-TNF
antibodies.

Study Selection We included randomized, placebo-controlled trials of the 2
licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks
or more in patients with rheumatoid arthritis. Nine trials met our inclusion
criteria, including 3493 patients who received anti-TNF antibody treatment
and 1512 patients who received placebo.

Data Extraction Data on study characteristics to assess study quality and
intention-to-treat data for serious infections and malignancies were
abstracted. Published information from the trials was supplemented by direct
contact between principal investigators and industry sponsors.

Data Synthesis We calculated a pooled odds ratio (Mantel-Haenszel methods
with a continuity correction designed for sparse data) for malignancies and
serious infections (infection that requires antimicrobial therapy and/or
hospitalization) in anti-TNF­treated patients vs placebo patients. We
estimated effects for high and low doses separately. The pooled odds ratio
for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for
serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly
more common in patients treated with higher doses compared with patients who
received lower doses of anti-TNF antibodies. For patients treated with
anti-TNF antibodies in the included trials, the number needed to harm was
154 (95% CI, 91-500) for 1 additional malignancy within a treatment period
of 6 to 12 months. For serious infections, the number needed to harm was 59
(95% CI, 39-125) within a treatment period of 3 to 12 months.

Conclusions There is evidence of an increased risk of serious infections
and a dose-dependent increased risk of malignancies in patients with
rheumatoid arthritis treated with anti-TNF antibody therapy. The formal
meta-analysis with pooled sparse adverse events data from randomized
controlled trials serves as a tool to assess harmful drug effects.

Author Affiliations: Division of Rheumatology and Department of Internal
Medicine, Mayo Clinic College of Medicine, Rochester, Minn (Drs Bongartz and
Matteson); Department of Health Sciences, University of Leicester,
Leicester, England (Dr Sutton); MRC Biostatistics Unit, Institute of Public
Health, Cambridge, England (Mr Sweeting); Northwest Institute for Bio-Health
Informatics, University of Manchester, Manchester, England (Dr Buchan);
Knowledge and Encounter Research Unit and Department of Medicine, Mayo
Clinic College of Medicine, Rochester, Minn (Dr Montori).