Rheumatoid Arthritis - T cell Costimulation: Abatacept
Abatacept is a molecule targeting T cell costimulation and activation. It is approved for the treatment of RA in patients with established RA who have not responded to DMARDS. It has not been studied however in patients with early RA who have not yet received a DMARD.
Abstract 1213: The Efficacy and Safety of Abatacept in Methotrexate-naïve Patients with Early Erosive Rheumatoid Arthritis and Poor Prognostic Factors
Authors:
R. Westhovens, M. Robles, S. Nayiager, J. Wollenhaupt, P. Durez, J. Gomez-Reino, W. Grassi, B. Haraoui, W. Shergy, SH. Park, H. Genant, C. Peterfy, J-C. Becker, A. Covucci, R. Helfrick, J. Bathon.
Background:
In early RA, erosions and seropositivity (RF/anti-CCP) are indicators of poor prognosis. Here we present 1-year results from a 2-year study of abatacept (ABA) in seropositive MTX-naïve patients with early erosive RA.
Methods:
This was a Phase IIIb, double-blind study, patients with RA for ≤2 yrs were randomized (1:1) to receive ABA + MTX or placebo + MTX. Patients were MTX naïve, RF/anti-CCP positive and had evidence of erosions on Xrays of the hands, wrists or feet. ABA was administered at ~10 mg/kg according to weight range; MTX was initiated at 7.5 mg/week and titrated to 20 mg/week by Week 8. Primary endpoints were: DAS28 (CRP)-defined remission (<2.6) and joint damage progression (Genant-modified Sharp total score [TS]1) at Year 1. Other efficacy measures included ACR responses. Safety was monitored throughout.
Results:
Patients had high baseline disease activity with short disease duration (Table), and were positive for RF (96.5%), anti-CCP (89.0%) or both (89.0%). Of the 256 and 253 patients treated with ABA + MTX or MTX alone, 90.6 and 89.7% completed Year 1, respectively. Fewer patients in the ABA + MTX vs MTX group discontinued due to lack of efficacy (0 vs 3.2%) or AEs (3.5 vs 4.3%). Rates of AEs and SAEs were similar in each group (AEs: 84.8 vs 83.4% and SAEs: 7.8 vs 7.9% of patients in the ABA + MTX vs MTX groups, respectively). Serious infections were more common in ABA + MTX [2 (0.8%)] than with MTX alone [4 (1.6%)]. Autoimmune disorders occurred in 6 (2.3%) vs 5 (2.0%) ABA + MTX vs MTX-treated patients, respectively; no malignancies were reported. Acute infusion reactions (mostly mild/moderate), occurred in 16 (6.3%) vs 5 (2.0%) of ABA + MTX- vs MTX-treated patients.
| Table. Baseline characteristics and clinical efficacy at Year 1, by treatment group | ||
| ABA + MTX (N=256) | MTX (N=253) | |
| Baseline characteristics | ||
| Mean tender joints, n (SD) | 31.3 (14.8) | 30.8 (14.0) |
| Mean swollen joints, n (SD) | 22.9 (11.3) | 21.9 (10.1) |
| Disease duration, months | 6.2 (7.5) | 6.7 (7.1) |
| Mean MTX dose | 18 mg | 19 mg |
| Patients achieving DAS28 (CRP)-defined remission, % (95% CI) | 41.4* (35.4, 47.4) |
23.3 (18.1, 28.5) |
| ACR 50 responders, % (95% CI) | 57.4* (51.4, 63.5) |
42.3 (36.2, 48.4) |
| ACR 70 responders, % (95% CI) | 42.6* (36.5, 48.6) |
27.3 (21.8, 32.8) |
| MCR (ACR 70 for 6 consecutive months), % (95% CI) | 27.3* (21.9, 32.8) |
11.9 (7.9, 15.8) |
| Mean change from baseline in TS, n (SD) | 0.63†‡ (1.74) |
1.06‡ (2.45) |
| *p<0.001 and †p=0.04 for ABA + MTX vs MTX alone; ‡N=242 | ||
Conclusions:
Abatacept + MTX provided significantly better efficacy and favorable safety compared with MTX alone in an MTX-naïve population with early erosive RA and poor prognostic factors.
Editorial Comment:
The use of abatacept is currently limited to patients failing MTX. These results demonstrate increased efficacy and decreased radiographic progression at one year with ABA+MTX compared to MTX alone in patients who are MTX-naïve with early RA. As with all of the clinical trials of patients with early RA, patients were enrolled with very active disease and poor prognostic features (erosions, CCP/RF), and as in other studies, the radiographic differences are driven by a small group of patients with very rapid progression. Before using a combination biological therapy approach in all patients with early RA it is important to recognize that aggressively dosed MTX as monotherapy is an effective strategy in many patients. As noted with the TNF antagonist studies of early RA patients, we still need studies to compare an induction/withdrawal approach compared to a step up approach anchored with aggressive MTX in patients who are more similar to most of those encountered in clinical practice.
Editor: Clifton Bingham, III, M.D.
