Outcomes of treatment with Humira in patients with active RA receiving concomitant MTX therapy

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Arthritis Rheum. 2004 May;50(5):1400-11.

Radiographic, clinical, and functional outcomes of treatment with

adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in

patients with active rheumatoid arthritis receiving concomitant

methotrexate therapy: a randomized, placebo-controlled, 52-week trial.

Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS,

Fischkoff SA, Chartash EK.

University of Toronto, Toronto, Ontario M5G 1X5, Canada.

OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory

cytokine that mediates inflammatory synovitis and articular matrix

degradation in rheumatoid arthritis (RA). We investigated the ability of

adalimumab, a human anti-TNF monoclonal antibody, to inhibit the

progression of structural joint damage, reduce the signs and symptoms,

and improve physical function in patients with active RA receiving

concomitant treatment with methotrexate (MTX). METHODS: In this

multicenter, 52-week, double-blind, placebo-controlled study, 619

patients with active RA who had an inadequate response to MTX were

randomized to receive adalimumab 40 mg subcutaneously every other week

(n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or

placebo (n = 200) plus concomitant MTX. The primary efficacy end points

were radiographic progression at week 52 (total Sharp score by a

modified method [TSS]), clinical response at week 24 (improvements of at

least 20% in the American College of Rheumatology core criteria

[ACR20]), and physical function at week 52 (disability index of the

Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was

statistically significantly less radiographic progression, as measured

by the change in TSS, in the patients receiving adalimumab either 40 mg

every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8

+/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P <

or = 0.001 for each comparison). In addition, there were statistically

significant changes in the components of the TSS. At week 24, ACR20

responses were achieved by 63% and 61% of patients in the adalimumab 40

mg every other week and 20 mg weekly groups, respectively, versus 30% of

patients in the placebo group (P < or = 0.001 for each comparison). At

week 52, ACR20 responses were achieved by 59% and 55% of patients taking

adalimumab 40 mg every other week and 20 mg weekly, respectively, versus

24% of patients taking placebo (P < or = 0.001 for each comparison). At

week 52, physical function as measured by the HAQ demonstrated

statistically significant improvement with adalimumab 40 mg every other

week and 20 mg weekly compared with placebo (mean change in HAQ

score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for

each comparison). A total of 467 patients (75.4%) completed 52 weeks of

treatment. Adalimumab was generally well tolerated. Discontinuations

occurred in 22.0% of adalimumab-treated patients and in 30.0% of

placebo-treated patients. The rate of adverse events (both serious and

nonserious) was comparable in the adalimumab and placebo groups,

although the proportion of patients reporting serious infections was

higher in patients receiving adalimumab (3.8%) than in those receiving

placebo (0.5%) (P < or = 0.02), and was highest in the patients

receiving 40 mg every other week.

CONCLUSION: In this 52-week trial, adalimumab was more effective than

placebo at inhibiting the progression of structural joint damage,

reducing the signs and symptoms, and improving physical function in

patients with active RA who had demonstrated an incomplete response to

MTX.

PMID: 15146409

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Mayo Clinic in Rochester

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s Hopkins Medicine

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