Research on Methotrexate with Etanercept

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Etanercept Plus Methotrexate: How

Effective in RA?

Paper: A trial of etanercept, a recombinant tumor

necrosis factor

receptor:Fc fusion protein, in patients with

rheumatoid arthritis receiving

methotrexate.

Authors: Weinblatt ME, et al.

Ref: N Engl J Med 1999;340:253-259.

Type: Clinical Study

Summary: Methotrexate is often considered a

first-line

choice for the treatment of rheumatoid

arthritis (RA). RA

activity can be decreased by methotrexate but

many patients

continue to have persistent disease despite

chronic therapy.

Tumor necrosis factor (TNF) is a

proinflammatory cytokine

with a role in the development of RA.

Etanercept is a

genetically engineered fusion protein

consisting of two

identical chains of the recombinant

TNF-receptor p75

monomer fused with the Fc domain of human

IgGl.

Consequently, TNF is bound and inactivated by

etanercept.

This study was conducted to examine if

etanercept, in

combination with methotrexate, could decrease

disease

activity in patients already being treated

with long-term

methotrexate but who continue to have active

disease. 89

patients were recruited into the study and

were randomized

in a 1:2 fashion, 30 to receive placebo and

methotrexate and

59 to receive etanercept and methotrexate for

24 weeks. The

proportion of patients who met the ACR

preliminary criteria

for improvement (ACR 20) at 24 weeks was the

primary

endpoint.

At the end of therapy, the

etanercept/methotrexate group had

significantly improved outcomes at all

endpoints. 71% of

patients in the etanercept/methotrexate group

and 27% of

patients in the placebo/methotrexate met the

ACR 20 criteria

at 24 weeks (p<0.001). Etanercept was well

tolerated; the

only event being more common than in the

placebo group

was injection site reactions, which were mild.

Antibodies to

etanercept were found in only one patient.

The authors concluded that combination of

etanercept and

methotrexate offers a new alternative to those

patients

whose rheumatoid arthritis continues to be

active despite

methotrexate treatment.