Background The combination of etanercept (ETN) and methotrexate can inhibit the progression of joint destruction. However, biological therapy imposes to an economic burden on patients. To reduce the treatment cost of biological agents, low-dose ETN has been administered without supporting evidence of effectiveness. We previously reported the results of the PRECEPT study that evaluated the clinical ability of low-dose ETN (25 mg/week) to prevent joint destruction in rheumatoid arthritis (RA) patients. Low and standard doses of ETN similarly affected clinical manifestations but the low dose did not suppress joint destruction as effectively1.
Objectives To determine predictive factors for radiographic progression in RA patients administered with low- and standard-dose ETN using a sub-analysis of the PRECEPT study.
Methods This prospective, randomized, open-label study was registered with the UMIN Clinical Trials Registry (UMIN000001798). Seventy patients were randomly assigned to receive either 25 or 50 mg of ETN for 52 weeks. The primary end point was a variation in the modified total Sharp score (TSS) after one year. Progression was estimated as deltaTSS >0.5 and progression rates were compared between the groups. Correlations with radiographic progression were investigated by logistic regression analysis. Data were statistically analyzed using Stat view version 5.0 software and values of p<0.05 were considered significant.
Results Similar clinical results were observed between the low and standard doses of ETN; however, the radiographic progression rates significantly differed (63.3% vs. 32.3%, p=0.041; Table 1). The predictive factors for a significantly increased risk of radiographic progression were low-dose (25 mg/week) ETN, positive rheumatoid factor (RF) and age. The odds ratios (OR) of low-dose ETN, RF positivity and age were 4.63, 27.08 and 1.08, respectively. Only RF positivity significantly increased the risk of radiographic progression in the low-dose group (OR, 22.92; 95% CI, 1.77 – 297.31; p=0.017).
Conclusions Older RA patients on low-dose ETN therapy who are RF positive have the potential for radiographic progression and the standard dose should be recommended. We actually recommend the standard dose when patients with RA can afford the cost. Joint destruction progresses more rapidly in patients with RA administered with a low, than a standard dose of ETN. Being RF positive was a predictor of radiographic progression in such patients receiving a low dose of ETN.
Tada M, Okano T, Sugioka Y, et al. Prevention of cartilage destruction by etanercept (PRECEPT) study: the comparison of joint destruction between low-dose and standard-dose etanercept in rheumatoid arthritis. Arthritis Rheum. 2011; 63(Suppl) Abstract S151.
Disclosure of Interest M. Tada: None Declared, T. Koike Grant/Research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, T. Okano: None Declared, Y. Sugioka: None Declared, K. Mamoto: None Declared, S. Wakitani: None Declared, H. Nakamura Grant/Research support from: Chugai Pharmaceutical, Astellas Pharma Inc.,Janssen Pharmaceutica, GlaxoSmithKline, Pfizer Inc. and Daiichi Sankyo, INC., Speakers Bureau: Ono Pharmaceutical