Defining and characterizing sustained remission in patients with rheumatoid arthritis

Abstract

The objective of this study is to characterize stability and clinical features of patients with rheumatoid arthritis (RA) in sustained remission. Combination therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has increased remission rates in RA but optimal regimens to maintain remission are unknown. We describe Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run-in period of longitudinal observation. Patients in Simplified Disease Activity Index (SDAI) remission (score ≤ 3.3) receiving etanercept and methotrexate were screened and had to maintain remission over 3 run-in visits/24 weeks before randomization to combination therapy or withdrawal of etanercept or methotrexate. Baseline characteristics were examined for predictive factors for maintaining remission. As of November 2016, 141 patients have enrolled; of these, 64 have been randomized, 34 were ineligible after run-in, and 43 are in run-in period; 70% have completed run-in. Enrolled and randomized patients, respectively, had mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years; mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD) methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores 1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission based on 28 joints and 66/68 joints, respectively. No enrollment characteristic predicted successful completion of run-in. Two-thirds of patients considered to be in remission at enrollment sustained remission through 24 weeks. Baseline characteristics of enrolled patients and those who completed run-in were comparable.

Keywords: Etanercept; Methotrexate; Remission; Rheumatoid arthritis.

Conflict of interest statement

J.R. Curtis is a consultant for AbbVie Inc., Amgen Inc., Bristol-Myers Squibb Company, Corrona, Eli Lilly & Co., Janssen Global Services, LLC, Myriad Pharma, Pfizer Inc., Roche/Genentech, and UCB. M. Trivedi, G.S. Park, D.H. Collier, G.A. Aras, and J. Chung are employees and shareholders of Amgen Inc. B. Haraoui serves as a consultant for AbbVie Inc., Amgen Inc., Bristol-Myers Squibb Company, Merck & Co., Inc., Pfizer Inc., Roche, and UCB and has received speaking fees from Pfizer Inc. and UCB. P. Emery has undertaken clinical trials and provided expert advice to AbbVie Inc., Bristol-Myers Squibb Company, Eli Lilly & Co., F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme Corp., Novartis, Pfizer Inc., Samsung, Sandoz International GmbH, and UCB.

Figures

Fig. 1

Study schema

Fig. 2

SDAI scores at 3 run-in visits. Individual patient SDAI scores during the 3 run-in visits are shown at approximately − 168 days (24 weeks prior to planned randomization on day 1), − 84 days (12 weeks prior to randomization), and day − 7 (just prior to randomization). Dashed lines indicate SDAI scores of 3.3 and 11. SDAI = Simplified Disease Activity Index

Fig. 3

Boolean remission at run-in visits. The percentages of patients with remission using Boolean definitions based on 28 joints (black bars), 28 joints and including feet and ankle joints (gray bars), and 66/68 joints (white bars) are shown. n = number of patients in Boolean remission

Fig. 4

Proportion of patients remaining in the study through the run-in period. Tick marks represent censored observations, and error bars represent 95% confidence intervals