La evaluación de mantenimiento de reimssion con etanercept más metotrexato de dosis reducida, metotrexato solo, o placebo en pacientes con principios de arthirtis reumatoide que alcanzaron la remisión con etanercept y metotrexato: el estudio PREMIO

BACKGROUND:

During Phase 1 of the 52 wk open-label PRIZE study treatment of patients (pts) with early (mean 6 mos.) moderate-severe rheumatoid arthritis (RA), who were methotrexate (MTX)/biologic naïve, with 50 mg etanercept (ETN) + 10-25 mg MTX yielded a 70% remission rate with no significant radiographic progression.1 Pts achieving remission in Phase I were randomized to a double-blind 39-wk period of reduced (25mg) ETN + MTX or withdrawn (MTX alone or placebo, PBO) therapy (PRIZE Phase 2).

OBJECTIVES:

To assess sustained remission (DAS28 and ACR/EULAR Boolean [AEB]), other clinical, radiographic, and safety outcomes in pts subsequently treated with reduced dose ETN or PBO after remission induction during PRIZE Phase 1.

METHODS:

Pts achieving DAS28 remission by wk 52 (≤3.2 at wk 39, <2.6 at wk 52) in Phase 1 (n=193) were randomized 1:1:1 to ETN25

/MTX:

MTX + PBO injection: PBO capsules + PBO injection at wk 52. Pts with DAS28>3.2 (> low disease activity, LDA) received corticosteroid boosts at wks 56 or 64; pts not achieving LDA at the next visit withdrew. Remission and other standard clinical outcomes were assessed. Odds ratios and significance were determined by logistic regression models.

RESULTS:

ETN/MTX resulted in a significantly higher proportion of pts in sustained and AEB remission than MTX alone or PBO. More ETN/MTX treated pts achieved DAS28 LDA than PBO. Over Phase 2 radiographic progression (mTSS >0.5) occurred in <12% of pts, with no significant difference between treatment arms; at Phase 1 baseline the mTSS scores were 8.06, 8.46 and 7.59 for ETN25/MTX, MTX and PBO, with changes of 0.44, -0.5 and 1.41 by last observations in Phase 2 (LOCF), indicating no clinically relevant radiographic progression in any of these treatment groups ETN/MTX treatment resulted in more pts achieving ACR50 and 70 than PBO. There were no unexpected safety findings.

CONCLUSIONS:

Of the moderate-severe early RA pts achieving DAS28 remission during a 52 wk induction (50 mg ETN/MTX in PRIZE Phase 1), 63.5% maintained remission (DAS28<2.6 at wk 76 & 91 visits) with ETN25/MTX, 38.5% with MTX and 23% with PBO over 39 subsequent wks. There was no significant radiographic progression in any treatment group. There were no unexpected safety findings.