Safety and efficacy of alternate-day corticosteroid treatment as adjunctive therapy for rheumatoid arthritis: a comparative study
Corticosteroids (CSs), used to treat rheumatoid arthritis (RA), confer a risk of adverse events (AEs). This study investigated the safety and efficacy of alternate-day (QOD) CS therapy for RA. All patients (> 18 years) who started oral CS therapy for RA, between 2005 and 2014, at our hospital were retrospectively analysed. The patients were divided into the daily (QD) and QOD CS therapy groups to investigate the rates of CS-related major AEs (infection, diabetes, hypertension, cardiovascular events and fragility fractures) within the first year of treatment. The number of patients free from CS treatment at 1 year and the mean decreases in C-reactive protein (CRP) levels at 1 month were also investigated. In total, 138 patients were analysed (QD group, 68; QOD group, 70). The maximum daily CS dose was not significantly different between the two groups, but the annual cumulative dose was significantly lower in the QOD group (P < 0.01). The infection rate was significantly lower in the QOD group (24.3%) than in the QD group (50.0%; P < 0.01), whereas the other AE rates were similar between the groups. The CS-free rate at 1 year was significantly higher in the QOD group (58.6%) than in the QD group (26.5%; P < 0.01). The mean CRP decreases over 1 month of CS therapy were not significantly different between the groups. QOD CS treatment leads to a lower infection rate and less CS dependence than does daily treatment; both RA treatments are equally effective.
KeywordsAdverse events Corticosteroids Infection Rheumatoid arthritis
The authors thank Hideki Nakajima for technical support.
Compliance with ethical standards
The study was approved by the Ethics Committee of St. Luke’s International Hospital (approval number, 14-R162).
- 2.Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52:3381–3390CrossRefPubMedGoogle Scholar
- 3.Nam JL, Villeneuve E, Hensor EM, Conaghan PG, Keen HI, Buch MH, Gough AK, Green MJ, Helliwell PS, Keenan AM, Morgan AW, Quinn M, Reece R, van der Heijde DM, Wakefield RJ, Emery P (2014) Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis 73:75–85CrossRefPubMedGoogle Scholar
- 4.Choy EH, Kingsley GH, Khoshaba B, Pipitone N, Scott DL, Intramuscular Methylprednisolone Study Group (2005) A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs. Ann Rheum Dis 64:1288–1293CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW, Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T, QUEST-RA Group (2009) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther 11:R7PubMedPubMedCentralGoogle Scholar
- 7.Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poór G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76:960–977CrossRefPubMedGoogle Scholar
- 8.van der Goes MC, Jacobs JW, Boers M, Andrews T, Blom-Bakkers MA, Buttgereit F, Caeyers N, Cutolo M, Da Silva JA, Guillevin L, Kirwan JR, Rovensky J, Severijns G, Webber S, Westhovens R, Bijlsma JW (2010) Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis 69:1913–1319CrossRefPubMedGoogle Scholar
- 10.van der Goes MC, Jacobs JW, Boers M, Andrews T, Blom-Bakkers MA, Buttgereit F, Caeyers N, Choy EH, Cutolo M, Da Silva JA, Guillevin L, Holland M, Kirwan JR, Rovensky J, Saag KG, Severijns G, Webber S, Westhovens R, Bijlsma JW (2010) Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 69:1015–1021CrossRefPubMedGoogle Scholar
- 11.van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136:1–12CrossRefPubMedGoogle Scholar
- 12.Capell HA, Madhok R, Hunter JA, Porter D, Morrison E, Larkin J, Thomson EA, Hampson R, Poon FW (2004) Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis 63:797–803CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW (2006) Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 65:285–293CrossRefPubMedGoogle Scholar
- 15.Strehl C, Bijlsma JW, de Wit M, Caeyers N, Cutolo M, Dasgupta B, Dixon WG, Geenen R, Huizinga TW, Kent A, de Thurah AL, Listing J, Mariette X, Ray DW, Scherer HU, Seror R, Spies CM, Tarp S, Wiek D, Winthrop KL, Buttgereit F (2016) Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis 75:952–957CrossRefPubMedGoogle Scholar
- 20.Migita K, Sasaki Y, Ishizuka N, Arai T, Kiyokawa T, Suematsu E, Yoshimura M, Kawabe Y, Matsumura R, Akagawa S, Mori S, Shirai M, Watanabe Y, Minami N, Soga T, Owan I, Ohshima S, Yoshizawa S, Matsui T, Tohma S, Bito S (2013) Glucocorticoid therapy and the risk of infection in patients with newly diagnosed autoimmune disease. Medicine 92(5):285Google Scholar
- 21.Mor A, Berencsi K, Nielsen JS, Rungby J, Friborg S, Brandslund I, Christiansen JS, Vaag A, Beck-Nielsen H, Sørensen HT, Thomsen RW (2016) Rates of community-based antibiotic prescriptions and hospital-treated infections in individuals with and without type 2 diabetes: a Danish nationwide cohort study, 2004-2012. Clin Infect Dis 63:501–511CrossRefPubMedGoogle Scholar
- 22.Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, Ghogomu ET, Coyle D, Clifford T, Tugwell P6 Wells GA (2015) Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet 386:258–265CrossRefPubMedPubMedCentralGoogle Scholar