Recent trends in use of nonbiologic DMARDs and evaluation of their continuation rates in single and dual combination therapies in rheumatoid arthritis patients in Japan
We aim to examine changes in usage of nonbiologic, disease-modifying antirheumatic drugs (DMARDs) and evaluate their continuation rates in Japan.
We analyzed DMARD treatment data for 3,734 patients with rheumatoid arthritis (RA) from 1998 to 2009 at Juntendo Hospital in Tokyo, Japan. The DMARD usage rate per month was determined to evaluate RA treatment history in the last decade. We also evaluated continuation rates of nonbiologic DMARDs in single and combination therapies and number of nonbiologic DMARD combination therapies used in each patient.
We found that nonbiologic DMARD usage has dramatically changed in the last decade, with the most commonly used DMARD shifting from bucillamine to methotrexate (MTX). MTX showed the highest continuation rate; however, much lower continuation rate was observed when used alone rather than in combination treatments. Further, MTX was also used in the highest number of different combination therapies for a particular patient.
These findings indicate that single MTX treatment may be unable to keep patients in clinical remission or lower disease activity compared with several combination therapies. Recent change in permitted maximum dosage of MTX from 8 to 16 mg/week may improve its efficacy and continuation rate in treating Japanese RA patients.
KeywordsCombination therapy DMARD continuation rate Japan Monotherapy Rheumatoid arthritis
Conflict of interest
- 6.Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381–90.PubMedCrossRefGoogle Scholar
- 7.Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, et al. A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs. Mod Rheumatol. 2009;19:273–82.PubMedCrossRefGoogle Scholar
- 17.Yamanaka H, Inoue E, Tanaka E, Nakajima A, Taniguchi A, Terai C, et al. Influence of methotrexate dose on its efficacy and safety in rheumatoid arthritis patients: evidence based on the variety of prescribing approaches among practicing Japanese rheumatologists in a single institute-based large observational cohort (IORRA). Mod Rheumatol. 2007;17:98–105.PubMedCrossRefGoogle Scholar
- 18.Visser K, Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E initiative. Ann Rheum Dis. 2009;68:1086–93.PubMedCrossRefGoogle Scholar
- 20.Ichikawa Y, Shinozawa T, Yoshida T, Kameda H, Suzuki Y, Kawai S, et al. Methotrexate and salazosulfapyridine in the long-term treatment of rheumatoid arthritis. Ryumachi. 1995;35:663–70 (in Japanese).Google Scholar
- 21.Nagaoka S, Nakamura M, Senuma A, Sekiguchi A. A clinical trial of low dose methotrexate therapy in patients with rheumatoid arthritis. Nihon Rinsho Meneki Gakkai Kaishi. 2005;28:389–97 (in Japanese).Google Scholar
- 22.van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, van Zeben D, Kerstens PJ, Gerards AH, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. Ann Rheum Dis. 2007;66:1356–62.PubMedCrossRefGoogle Scholar
- 26.Attar SM. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. A hospital-based study. Saudi Med J. 2010;30:909–15.Google Scholar