Etanercept/MTX study shows sustained remission, reversal of joint damage possible in RA

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Rheumawire

Feb 27, 2004

Etanercept/MTX study shows sustained remission, reversal of joint damage

possible in RA

Stockholm, Sweden - Fifty-two-week data from the Trial of Etanercept and

Methotrexate with Radiographic Patient Outcomes (TEMPO) trial show that

the combination of etanercept (Enbrel®; Amgen/Wyeth) and methotrexate is

better than either treatment alone in patients with rheumatoid arthritis

(RA). Dr Lars Klareskog and colleagues report in the February 28, 2004

issue of the Lancet that just over one third of patients treated with

the combination were in remission at 52 weeks, compared with one sixth

of those treated with etanercept and one eighth of those on methotrexate

[1].

Even more impressive is that the combination actually reversed

radiographic joint damage in many patients, dropping the total Sharp

score by 0.54 (95% CI -1.00 to -0.07).

" Notably, combination therapy resulted in mean negative radiographic

progression scores with the entire 95% CI below zero, " Klareskog writes.

Wyeth Research sponsored the TEMPO trial as part of a postapproval

commitment to the European Agency for the Evaluation of Medicinal

Products. Preliminary data were presented at a company-sponsored

satellite symposium at last summer's EULAR meeting and sparked immediate

discussion of the data showing a reversal in radiographic progression.

The multicenter, double-blind, phase 3 study randomized 682 patients to

treatment with etanercept 25 mg (sc once/wk), oral methotrexate (up to

20 mg every week), or the combination. The primary efficacy end point

was the numeric index of the ACR response (ACR-N) area under the curve

(AUC) at 24 weeks. The primary radiographic end point was the change in

total joint damage at 52 weeks. This was assessed by modified Sharp

score, which combines measures of joint erosion and joint-space

narrowing. Patients had RA for a mean of more than 6 years.

" Repair of joint damage on an individual joint level has been suggested

by various investigators in case reports and by results of studies

specifically addressing if repair is possible. Our results suggest that

repair induced by treatment may be possible on a group level, " Klareskog

writes.

" Remission has been described as the goal of treatment for rheumatoid

arthritis, yet published reports of success in achieving this goal are

scarce. Almost 3 times as many patients in the combination group were in

remission at 2 consecutive time points compared with either monotherapy.

This finding shows that the goal of sustained remission is reachable in

many patients with established rheumatoid arthritis, " the investigators

write.

Remission was defined as a disease activity scale (DAS) score of less

than 1.6. At 52 weeks, 35% of patients treated with the combination were

in remission, compared with 16% of patients treated with etanercept and

13% of those treated with methotrexate.

Klareskog reports that the primary efficacy end point (ACR-N AUC at 24

weeks) was 18.3%-years for the combination group, 14.7%-years for

etanercept, and 12.2%-years for methotrexate (p<0.001 favoring the

combination vs either solo treatment).

Significantly, more combination patients achieved ACR20 at 1 year (85%

vs 76% with etanercept and 75% with methotrexate). Similar differences

were seen in patients achieving ACR50 and ACR70.

Also, significantly fewer patients withdrew for lack of efficacy from

the combination group (n=6) than from either of the other groups (n=16,

p=0.0282, and 12, p=0.0027, respectively).

However, " combination treatment should not be considered the first

option, " Klareskog warns. " That is still methotrexate or another

disease-modifying antirheumatic drug (DMARD). Only after they have

failed should TNF blockade be considered. The novel finding is that

etanercept should then mainly be considered in combination with

methotrexate, not alone. "

Janis

Source

1. Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect

of the combination of etanercept and methotrexate compared with each

treatment alone in patients with rheumatoid arthritis: double-blind

randomized controlled trial. Lancet 2004; 363:675-681.

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Mayo Clinic in Rochester

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s Hopkins Medicine

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