Step-up combination therapy with mizoribine for the treatment of patients with rheumatoid arthritis

Objective:To determine the efficacy and safety of step-up therapy with disease-modifying antirheumatic drugs (DMARDs), including mizoribine, in the treatment of patients with rheumatoid arthritis (RA). In addition,we aimed to identify the characteristics of patients who would benefit from step-up th...

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Published inClinical Rheumatology and Related Research Vol. 26; no. 4; pp. 282 - 290
Main Author Suzuki, Kimihiro
Format Journal Article
LanguageJapanese
Published The Japanese Society for Clinical Rheumatology and Related Research 30.12.2014
一般社団法人 日本臨床リウマチ学会
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ISSN0914-8760
2189-0595
DOI10.14961/cra.26.282

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Abstract Objective:To determine the efficacy and safety of step-up therapy with disease-modifying antirheumatic drugs (DMARDs), including mizoribine, in the treatment of patients with rheumatoid arthritis (RA). In addition,we aimed to identify the characteristics of patients who would benefit from step-up therapy with mizoribine. Methods:Step-up therapy with DMARDs including mizoribine was administered to patients with RA who visited our hospital between October 2009 and end of September 2013. Patients who received mizoribine for at least 6months were enrolled as subjects. Results: The mean age of the subjects was72. 3years; of these, 11patients (55%) were aged 70-79 years and 4 patients (20%) were aged >80years. Prior to the initiation of mizoribine treatment, most patients were treated with an average of 3.5 agents. The mean number of agents used for treating these patients was 4.6, among which mizoribine was added last during treatment in 6patients. The change in Disease Activity Score-28-C-reactive protein (DAS 28-CRP) scores after initiation of step-up therapy with mizoribine were as follows:initial medical examination, 2.97; initiation of mizoribine treatment, 2.82; and final evaluation, 2.21. A significant decrease in the DAS 28-CRP score was observed, as compared to the baseline score (p=0.043). Adverse events were noted in 5 patients (25%), which included herpes zoster in 4patients, skin infection in 2 patients (toe paronychia and dermatitis, one in each patient), and acute exacerbation of chronic bronchitis in 1patient. All symptoms were resolved by drug withdrawal, or treatment with appropriate medication, and the step-up therapy could be resumed. Conclusion: We observed that step-up therapy with mizoribine has been shown to be a potentially useful treatment option for the treatment of RA patients having a complication and elderly patients who should be treated carefully.
AbstractList     Objective:To determine the efficacy and safety of step-up therapy with disease-modifying antirheumatic drugs (DMARDs), including mizoribine, in the treatment of patients with rheumatoid arthritis (RA). In addition,we aimed to identify the characteristics of patients who would benefit from step-up therapy with mizoribine.     Methods:Step-up therapy with DMARDs including mizoribine was administered to patients with RA who visited our hospital between October 2009 and end of September 2013. Patients who received mizoribine for at least 6months were enrolled as subjects.     Results: The mean age of the subjects was72. 3years; of these, 11patients (55%) were aged 70-79 years and 4 patients (20%) were aged >80years. Prior to the initiation of mizoribine treatment, most patients were treated with an average of 3.5 agents. The mean number of agents used for treating these patients was 4.6, among which mizoribine was added last during treatment in 6patients. The change in Disease Activity Score-28-C-reactive protein (DAS 28-CRP) scores after initiation of step-up therapy with mizoribine were as follows:initial medical examination, 2.97; initiation of mizoribine treatment, 2.82; and final evaluation, 2.21. A significant decrease in the DAS 28-CRP score was observed, as compared to the baseline score (p=0.043). Adverse events were noted in 5 patients (25%), which included herpes zoster in 4patients, skin infection in 2 patients (toe paronychia and dermatitis, one in each patient), and acute exacerbation of chronic bronchitis in 1patient. All symptoms were resolved by drug withdrawal, or treatment with appropriate medication, and the step-up therapy could be resumed.     Conclusion: We observed that step-up therapy with mizoribine has been shown to be a potentially useful treatment option for the treatment of RA patients having a complication and elderly patients who should be treated carefully. 目的:関節リウマチ(RA)に対するミゾリビン(MZR)を含めた抗リウマチ薬(DMARDs)ステップアップ療法の有効性と安全性について検討する.さらにミゾリビン・ステップアップ療法対象患者の特徴を明らかにする. 対象・方法:2009年10月から2013年9月末までに当院に来院したRA患者において,ミゾリビンを含むDMARDsステップアップ療法を行い,ミゾリビンを6か月以上投与した20名を対象とした. 結果:平均年齢は72.3歳であり,70~79歳は,11名(55%),80歳以上は4名(20%)であった.ミゾリビンの使用順位は,平均3.5剤目であった.平均併用薬剤数は4.6剤で,そのうち6例はミゾリビンが最後に追加されていた.ミゾリビン・ステップアップ療法によるDAS28-CRP値の推移は,初診時平均は2.97,ミゾリビン投与開始時は平均2.82,最終評価時には平均2.21となり,ミゾリビン投与開始時に比較して有意(p=0.043)に低下していた.有害事象は,5例(25%)に認められ,帯状疱疹4例,皮膚感染症(足趾爪囲炎1例,皮膚感染1例)2例,慢性気管支炎の急性増悪1例であった.各症状とも休薬ないし,治療薬の投与で軽快し,治療を再開することができた. 結論:ミゾリビン・ステップアップ療法は特に慎重な治療が求められる高齢者や合併症のあるRA患者集団などに対する治療法の選択枝の一つとして有用である可能性が示されたと考える.
Objective:To determine the efficacy and safety of step-up therapy with disease-modifying antirheumatic drugs (DMARDs), including mizoribine, in the treatment of patients with rheumatoid arthritis (RA). In addition,we aimed to identify the characteristics of patients who would benefit from step-up therapy with mizoribine. Methods:Step-up therapy with DMARDs including mizoribine was administered to patients with RA who visited our hospital between October 2009 and end of September 2013. Patients who received mizoribine for at least 6months were enrolled as subjects. Results: The mean age of the subjects was72. 3years; of these, 11patients (55%) were aged 70-79 years and 4 patients (20%) were aged >80years. Prior to the initiation of mizoribine treatment, most patients were treated with an average of 3.5 agents. The mean number of agents used for treating these patients was 4.6, among which mizoribine was added last during treatment in 6patients. The change in Disease Activity Score-28-C-reactive protein (DAS 28-CRP) scores after initiation of step-up therapy with mizoribine were as follows:initial medical examination, 2.97; initiation of mizoribine treatment, 2.82; and final evaluation, 2.21. A significant decrease in the DAS 28-CRP score was observed, as compared to the baseline score (p=0.043). Adverse events were noted in 5 patients (25%), which included herpes zoster in 4patients, skin infection in 2 patients (toe paronychia and dermatitis, one in each patient), and acute exacerbation of chronic bronchitis in 1patient. All symptoms were resolved by drug withdrawal, or treatment with appropriate medication, and the step-up therapy could be resumed. Conclusion: We observed that step-up therapy with mizoribine has been shown to be a potentially useful treatment option for the treatment of RA patients having a complication and elderly patients who should be treated carefully.
Author Suzuki, Kimihiro
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References 11) 旭化成ファーマ株式会社ブレディニン錠製品情報概要2011年5月作成
1) Oʼdell JR: Treating rheumatoid arthritis early: a window of opportunity?. Arthritis Rheum, 46:283, 2002.
8) 日本リウマチ友の会.関節リウマチ患者年 齢分布の変遷.http://www.nrat.or.jp/rhumatism/2010 101.html.
15) Nishimura K, Itoh K, Kuga Y, et al: Preventio of joint destruction in rheumatoid arthritis patients receiving combination methotrexate and mizoribine therapy: a two-years, multicenter open-comparison study to methotrexate monotherapy. Prog Med, 26:2163-2172, 2006.
10) 大西佐知子,岩本雅弘,簑田清次:高齢発症関節リウマチの治療.日本臨床免疫学会会誌,33:1-7,2010
7) Saag KG, Teng GG, Patlear NM, et al: American college of Rheumatology 2008 recommendations for use of non-biologic and biologic disease modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum, 59:762-784, 2008.
13) Kasama T, Wakabayashi K, Odai T, et al: Effects of low-dose mizoribine pulse therapy in combination with methotrexate in rheumatoid arthritis patients with an insufficient response to methotrexate. Mod Rheumatol, 19:395-400, 2009.
17) van Vollenhoven RF, Geborek P, Albertsson K, et al: Conventional combination treatment versus biological tratment in methotrexate-refractory early rheumatoid arthritis: 2year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet, 379:1712-1720, 2012.
2) Bakker MF, Jacobs J W, Verstappen SM, et al: Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility. Ann. Rheum. Dis, 66, Suppl3, iii56-60, 2007.
5) 北村登,武井正美:膠原病における免疫抑制薬の使い方―ミゾリビン.リウマチ科.51:52-57,2014
12) Tanaka E, Inoue E, Kawaguchi Y, et al: “Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients, based on analysis of data from a large-scale observational cohort study. Mod Rheumatol, 16:214-219, 2006.
6) 鈴木王洋,松本光世,堀越英之:発症2年以内の関節リウマチに対して,経口抗リウマチ薬を病勢に応じて積極的に使用した症例のレトロスペクティブ解析.臨床リウマチ,24:35-41,2012
4) 伊藤聡:経口抗リウマチ薬の実際の使い方を教えますミゾリビン.分子リウマチ治療,6:70-74,2013
14) Saito E, Ogawa T, Ogura T: Effect of Bucillamine- Mizoribine Combination Therapy in the Initial Treatment of Rheumatoid Arthritis. J New Rem & Clin, 61:842-851, 2012.
16) Oʼdell JR, Mikuls TR, Taylor TH, et al: Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med, 369:307-318, 2013.
3) Smolen JS, Aletaha D, Bijlsma JW, et al: Treating rhheumatoid arthritis to target: recommendations of an internatiol task force. Ann Rheum Dis, 69:631, 2010.
9) Ogasawara M, Tamura N, Onuma S, et al: Observational Cross-Sectional Study Revealing Less Aggressive Treatment in Japanese Elderly Than Nonelderly Patients With Rheumatoid Arhritis. J Clin Rheumatol, 16:370-374, 2010.
References_xml – reference: 12) Tanaka E, Inoue E, Kawaguchi Y, et al: “Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients, based on analysis of data from a large-scale observational cohort study. Mod Rheumatol, 16:214-219, 2006.
– reference: 14) Saito E, Ogawa T, Ogura T: Effect of Bucillamine- Mizoribine Combination Therapy in the Initial Treatment of Rheumatoid Arthritis. J New Rem & Clin, 61:842-851, 2012.
– reference: 11) 旭化成ファーマ株式会社ブレディニン錠製品情報概要2011年5月作成.
– reference: 3) Smolen JS, Aletaha D, Bijlsma JW, et al: Treating rhheumatoid arthritis to target: recommendations of an internatiol task force. Ann Rheum Dis, 69:631, 2010.
– reference: 5) 北村登,武井正美:膠原病における免疫抑制薬の使い方―ミゾリビン.リウマチ科.51:52-57,2014.
– reference: 13) Kasama T, Wakabayashi K, Odai T, et al: Effects of low-dose mizoribine pulse therapy in combination with methotrexate in rheumatoid arthritis patients with an insufficient response to methotrexate. Mod Rheumatol, 19:395-400, 2009.
– reference: 17) van Vollenhoven RF, Geborek P, Albertsson K, et al: Conventional combination treatment versus biological tratment in methotrexate-refractory early rheumatoid arthritis: 2year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet, 379:1712-1720, 2012.
– reference: 16) Oʼdell JR, Mikuls TR, Taylor TH, et al: Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med, 369:307-318, 2013.
– reference: 15) Nishimura K, Itoh K, Kuga Y, et al: Preventio of joint destruction in rheumatoid arthritis patients receiving combination methotrexate and mizoribine therapy: a two-years, multicenter open-comparison study to methotrexate monotherapy. Prog Med, 26:2163-2172, 2006.
– reference: 7) Saag KG, Teng GG, Patlear NM, et al: American college of Rheumatology 2008 recommendations for use of non-biologic and biologic disease modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum, 59:762-784, 2008.
– reference: 8) 日本リウマチ友の会.関節リウマチ患者年 齢分布の変遷.http://www.nrat.or.jp/rhumatism/2010 101.html.
– reference: 10) 大西佐知子,岩本雅弘,簑田清次:高齢発症関節リウマチの治療.日本臨床免疫学会会誌,33:1-7,2010.
– reference: 6) 鈴木王洋,松本光世,堀越英之:発症2年以内の関節リウマチに対して,経口抗リウマチ薬を病勢に応じて積極的に使用した症例のレトロスペクティブ解析.臨床リウマチ,24:35-41,2012.
– reference: 1) Oʼdell JR: Treating rheumatoid arthritis early: a window of opportunity?. Arthritis Rheum, 46:283, 2002.
– reference: 9) Ogasawara M, Tamura N, Onuma S, et al: Observational Cross-Sectional Study Revealing Less Aggressive Treatment in Japanese Elderly Than Nonelderly Patients With Rheumatoid Arhritis. J Clin Rheumatol, 16:370-374, 2010.
– reference: 2) Bakker MF, Jacobs J W, Verstappen SM, et al: Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility. Ann. Rheum. Dis, 66, Suppl3, iii56-60, 2007.
– reference: 4) 伊藤聡:経口抗リウマチ薬の実際の使い方を教えますミゾリビン.分子リウマチ治療,6:70-74,2013.
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SubjectTerms combination therapy
disease modifying anti-rheumatic drugs
mizoribine
rheumatoid arthritis
treat to target
Title Step-up combination therapy with mizoribine for the treatment of patients with rheumatoid arthritis
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