Low-Dose Prednisone Inclusion in a Methotrexate-Based, Tight Control Strategy for Early Rheumatoid Arthritis

BACKGROUND Treatment strategies for tight control of early rheumatoid arthritis (RA) are highly effective but can be improved. OBJECTIVE To investigate whether adding prednisone, 10 mg/d, at the start of a methotrexate (MTX)-based treatment strategy for tight control in early RA increases its effectiveness. DESIGN A 2-year, prospective, randomized, placebo-controlled, double-blind, multicenter trial (CAMERA-II [Computer Assisted Management in Early Rheumatoid Arthritis trial-II]). (International Standard Randomised Controlled Trial Number: ISRCTN 70365169) SETTING 7 hospitals in the Netherlands. PATIENTS 236 patients with early RA (duration <1 year). INTERVENTION Patients were randomly assigned to an MTX-based, tight control strategy starting with either MTX and prednisone or MTX and placebo. Methotrexate treatment was tailored to the individual patient at monthly visits on the basis of predefined response criteria aiming for remission. MEASUREMENTS The primary outcome was radiographic erosive joint damage after 2 years. Secondary outcomes included response criteria, remission, and the need to add cyclosporine or a biologic agent to the treatment. RESULTS Erosive joint damage after 2 years was limited and less in the group receiving MTX and prednisone (n = 117) than in the group receiving MTX and placebo (n = 119). The MTX and prednisone strategy was also more effective in reducing disease activity and physical disability, achieving sustained remission, and avoiding the addition of cyclosporine or biologic treatment. Adverse events were similar in both groups, but some occurred less in the MTX and prednisone group. LIMITATION A tight control strategy for RA implies monthly visits to an outpatient clinic, which is not always feasible. CONCLUSION Inclusion of low-dose prednisone in an MTX-based treatment strategy for tight control in early RA improves patient outcomes. PRIMARY FUNDING SOURCE Catharijne Foundation.

[1]  M. Boers,et al.  Effects of glucocorticoids on radiological progression in rheumatoid arthritis. , 2007, The Cochrane database of systematic reviews.

[2]  A. McMahon,et al.  Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial , 2004, The Lancet.

[3]  D. O'leary,et al.  Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis. , 2011, Arthritis and rheumatism.

[4]  G. Jürgens,et al.  Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons. , 2010, Arthritis and rheumatism.

[5]  Hyon K. Choi,et al.  Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7,527 patients. , 2003, Arthritis and rheumatism.

[6]  M. Makuuchi,et al.  Management of Hepatocellular Carcinoma in Japan: Consensus-Based Clinical Practice Guidelines Proposed by the Japan Society of Hepatology (JSH) 2010 Updated Version , 2011, Digestive Diseases.

[7]  Zhao-You Tang,et al.  Randomized controlled trial of screening for hepatocellular carcinoma , 2004, Journal of Cancer Research and Clinical Oncology.

[8]  J. Jacobs,et al.  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 , 2002, Annals of Internal Medicine.

[9]  R. Rau,et al.  Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. , 2005, Arthritis and rheumatism.

[10]  B. Dijkmans,et al.  Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis , 2007, Annals of the rheumatic diseases.

[11]  J. Jacobs,et al.  Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial) , 2007, Annals of the rheumatic diseases.

[12]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[13]  T. Pincus,et al.  Low-dose glucocorticoids in rheumatic diseases: introduction. , 2011, Clinical and experimental rheumatology.

[14]  K. Saag,et al.  From bone biology to clinical outcome: state of the art and future perspectives , 2010, Annals of the rheumatic diseases.

[15]  D. M. van der Heijde,et al.  Extended Report , 2022 .

[16]  N. Lameire.  Handbook of Chronic Kidney Disease Management , 2011, NDT Plus.

[17]  P. V. van Riel,et al.  Ups and downs in the treatment strategies of rheumatoid arthritis. , 2011, Rheumatology.

[18]  D. Symmons,et al.  EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis , 2009, Annals of the rheumatic diseases.

[19]  M. Boers.  Understanding the window of opportunity concept in early rheumatoid arthritis. , 2003, Arthritis and rheumatism.

[20]  G. Levine,et al.  2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. , 2011, Circulation.

[21]  Mahboob Rahman,et al.  Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: Risk reduction in a chronic inflammatory disease , 2011, Arthritis care & research.

[22]  D. M. van der Heijde,et al.  Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature , 2008, Annals of the rheumatic diseases.

[23]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[24]  C. Bombardier,et al.  Published Online First , 2007 .

[25]  M. Prevoo,et al.  Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. , 1995, Arthritis and rheumatism.

[26]  D. M. van der Heijde,et al.  Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research , 2008, Annals of the rheumatic diseases.

[27]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[28]  J. Kirwan,et al.  Reduced loss of hand bone density with prednisolone in early rheumatoid arthritis: results from a randomized placebo-controlled trial. , 2005, Archives of internal medicine.

[29]  B. Dijkmans,et al.  Blood pressure changes in patients with recent-onset rheumatoid arthritis treated with four different treatment strategies: a post hoc analysis from the BeSt trial , 2010, Annals of the rheumatic diseases.

[30]  M. Law.  Screening without evidence of efficacy , 2004, BMJ : British Medical Journal.

[31]  A Woolf,et al.  The links between joint damage and disability in rheumatoid arthritis. , 2000, Rheumatology.

[32]  T. Pincus,et al.  Are Long-Term Very Low Doses of Prednisone for Patients with Rheumatoid Arthritis as Helpful as High Doses Are Harmful? , 2002, Annals of Internal Medicine.

[33]  H. D. de Koning.  Mammographic screening: evidence from randomised controlled trials. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[34]  T. MacDonald,et al.  Taking Glucocorticoids by Prescription Is Associated with Subsequent Cardiovascular Disease , 2004, Annals of Internal Medicine.

[35]  John Wong,et al.  EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs , 2010, Annals of the rheumatic diseases.

[36]  R. Califf,et al.  The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. , 2008, American heart journal.

[37]  M. Sherman,et al.  Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: Incidence and prevalence of hepatocellular carcinoma in a North American urban population , 1995, Hepatology.

[38]  U. Steinseifer,et al.  In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves. , 2010, Thrombosis research.

[39]  G. Kitas,et al.  Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study , 2012, Arthritis Research & Therapy.

[40]  J. Jacobs,et al.  Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis , 2008, Annals of the rheumatic diseases.

[41]  P. Hannonen,et al.  Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial , 2010, Arthritis research & therapy.

[42]  M Cutolo,et al.  Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data , 2005, Annals of the rheumatic diseases.

[43]  R. Landewé,et al.  Economic aspects of treatment options in rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis , 2010, Annals of the rheumatic diseases.

[44]  P. V. van Riel,et al.  Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome. , 2010, Rheumatology.

[45]  J. Bruix,et al.  Screening for Liver Cancer: The Rush to Judgment , 2012, Annals of Internal Medicine.

[46]  M. Szklo,et al.  Longitudinal predictors of progression of carotid atherosclerosis in rheumatoid arthritis. , 2011, Arthritis and rheumatism.

[47]  P. Malfertheiner,et al.  Hepatocellular carcinoma (HCC): a global perspective. , 2010, Journal of clinical gastroenterology.

[48]  S. Frostick,et al.  Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE‐MODEL randomized trial , 2007, Journal of thrombosis and haemostasis : JTH.

[49]  S. Yusuf,et al.  Renal function and outcomes in acute coronary syndrome: impact of clopidogrel , 2007, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[50]  Rene Westhovens,et al.  COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. , 2002, Arthritis and rheumatism.

[51]  H. Poustchi,et al.  Feasibility of conducting a randomized control trial for liver cancer screening: Is a randomized controlled trial for liver cancer screening feasible or still needed? , 2011, Hepatology.

[52]  Luigi Solbiati,et al.  Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? , 2007, Hepatology.

[53]  L. Laine,et al.  Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. , 2006, The American journal of medicine.

[54]  P. Mease.  Improving the Routine Management of Rheumatoid Arthritis: The Value of Tight Control , 2010, The Journal of Rheumatology.

[55]  S. van der Linden,et al.  Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis , 1997, The Lancet.

[56]  Maurizio Cutolo,et al.  Treating rheumatoid arthritis to target: recommendations of an international task force , 2010, Annals of the rheumatic diseases.

[57]  R. Rau,et al.  An update on methotrexate , 2009, Current opinion in rheumatology.

[58]  D. Heijde,et al.  EFFECTS OF HYDROXYCHLOROQUINE AND SULPHASALAZINE ON PROGRESSION OF JOINT DAMAGE IN RHEUMATOID ARTHRITIS , 1989, The Lancet.

[59]  S. van der Linden,et al.  Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis , 2003, Annals of the rheumatic diseases.

[60]  J. Jacobs,et al.  Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility , 2007, Annals of the rheumatic diseases.

[61]  J. Craig,et al.  Effects of Antiplatelet Therapy on Mortality and Cardiovascular and Bleeding Outcomes in Persons With Chronic Kidney Disease , 2012, Annals of Internal Medicine.

[62]  A. Zanchetti,et al.  Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial. , 2010, Journal of the American College of Cardiology.

[63]  J. Jacobs,et al.  The clinical effect of glucocorticoids in patients with rheumatoid arthritis may be masked by decreased use of additional therapies. , 2004, Arthritis and rheumatism.