Background/Purpose: Subjects with moderately active rheumatoid arthritis (RA) have been shown to achieve and maintain low disease activity (LDA) and remission with anti-TNF therapy more successfully than subjects with high disease activity.1 Due to reimbursement and safety concerns, there has been growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response. The PRESERVE trial compared the efficacy and safety of continuing etanercept (ETN) 50 mg QW + methotrexate (MTX) (E50/M), reducing ETN from 50 mg to 25 mg QW + MTX (E25/M), and withdrawing ETN and giving placebo QW + MTX (P/M) over 52 weeks after sustained LDA had been induced during 9 months of E50/M treatment.
Methods: Subjects with moderately active RA (3.2<DAS28≤5.1) who achieved DAS28 LDA (DAS28 ≤3.2, avg wk 12–36 + at wk 36) or remission (DAS28 <2.6) on E50/M at wk 36 of Period 1 entered the double-blind Period 2. 604 subjects were randomized based on DAS28 LDA/remission to E50/M (n=202), E25/M (n=202), or P/M (n=200) for 52 wks. MTX was maintained at same dose throughout (15–25 mg). All statistical analyses were stratified by geographic region and DAS28 strata at randomization. Proportions were tested with chi-square tests; continuous endpoints with ANCOVA using Period 2 baseline DAS28 value as covariate; radiographic endpoints with rank-transformed ANCOVA.
Results: 497 subjects completed Period 2. The % of subjects maintaining DAS28 LDA at wk 88 was significantly higher in the E50/M (82.6%) and E25/M (79.1%) groups than P/M group (42.6%; P<0.0001 vs either ETN group). Significantly more subjects had a DAS28 score <2.6 at wk 88 on E50/M (66.7%) and E25/M (60.2%) than on P/M (29.4%; P<0.0001 vs either ETN group). Significantly more subjects on E50/M and E25/M achieved SDAI LDA and remission, ACR 20/50/70 responses, and a normal HAQ score (≤0.5) than on P/M (Table). The mTSS (units/y) change from baseline was significantly different between the E50/M (–0.06) and P/M (0.60; P=0.0259) groups, but not between the E25/M (0.05) and P/M (0.60; P=0.0696) groups, or the E50/M and E25/M (P=0.6737) groups. No significant differences in safety were observed. 35 subjects (5.8%) reported serious adverse events, including 2 deaths (0.3%) in the E50/M group due to pulmonary embolism and septicemia during Period 2.
Conclusions: This is the first trial for adults with moderately active RA despite MTX treatment evaluating both induction of DAS28 LDA, and clinical, functional, and radiographic outcomes with etanercept full-dose continuation, reduction, or elimination on a background of MTX. Subjects were significantly more likely to successfully maintain DAS28 LDA (and other clinical benefits) over 52 weeks with the 2 ETN treatment regimens, after a 9-month LDA induction, than with a step down to P/M. Further research is needed on the longer term implications of these 52-week observations.
1. Keystone E, et al. J Rheumatol 2009;36:522.
Disclosure: J. S. Smolen, Pfizer Inc, 2, Pfizer Inc, 5 ; E. Ilivanova, None; S. Hall, Pfizer Inc, 9 ; F. Irazoque-Palazuelos, Pfizer Inc, Roche, BMS, Janssen, and Abbott, 2, Pfizer Inc, Roche, and BMS, 8 ; M. C. Park, None; S. Kotak, Pfizer Inc, 3 ; C. Hammond, Pfizer Inc, 1, Pfizer Inc, 3 ; R. Pedersen, Pfizer Inc, 1, Pfizer Inc, 3 ; A. Szumski, None; A. S. Koenig, Pfizer Inc, 1, Pfizer Inc, 3 ; B. Vlahos, Pfizer Inc, 1, Pfizer Inc, 3 .