Drug Therapy for Early Rheumatoid Arthritis in Adults: A Systematic Review Update

Project Summary Title and Description

Title
Drug Therapy for Early Rheumatoid Arthritis in Adults: A Systematic Review Update
Description
The purpose of this systematic review is to update the 2012 Comparative Effectiveness Review that evaluated the benefits and harms of drug therapies for adults with rheumatoid arthritis (RA). This updated review has a targeted scope focusing solely on patients with early RA, defined as no more than one year of diagnosed disease. This report is intended to help health care decision makers -- patients, and clinicians, health system leaders, and policymakers, among others -- make well-informed decisions regarding early RA and thereby improve the quality of health care services.
Attribution
N/A
Authors of Report
N/A
Methodology description
To identify relevant published literature, we searched the following databases: MEDLINE® via PubMed, the Cochrane Library, Embase, and International Pharmaceutical Abstracts. Our literature searches included articles published from July 2010 to October 5, 2017. We manually searched the reference lists of included systematic reviews to supplement the main database searches. We ensured that our update added to the body of evidence found in the 2012 review, including new drugs approved by the U.S. Food and Drug Administration (FDA) or undergoing FDA review during our review period. We also searched the gray literature for unpublished studies relevant to this review, including: ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the New York Academy of Medicine’s Grey Literature Index, and Supplemental Evidence and Data information from targeted requests and from a Federal Register Notice (public invitation posted in the Federal Register to submit relevant study data to AHRQ on behalf of Evidence-based Practice Centers). To answer the Contextual Questions, we identified relevant literature opportunistically from our literature searches for KQs and used targeted literature searches to address remaining gaps in information.
PROSPERO
CRD42017079260
DOI
10.26300/wb4y-c965
Notes
All of the report's study data were entered retrospectively to SRDR via direct file uploading as Word documents. Included are four documents that list KQ-specific data for KQs 1, 2, 3, and 4, respectively, and 5 additional files that pertain to all of the KQs, and describe abbreviations and acronyms; summary of findings; detailed evidence tables; risk of bias ratings; and strength of evidence grades.
Funding Source
Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. For patients with early RA, do drug therapies differ in their ability to reduce disease activity, slow or limit the progression of radiographic joint damage, or induce remission?
2. For patients with early RA, do drug therapies differ in their ability to improve patient-reported symptoms, functional capacity, or quality of life?
3. For patients with early RA, do drug therapies differ in harms, tolerability, patient adherence, or adverse effects?
4. What are the comparative benefits and harms of drug therapies for early RA in subgroups of patients based on disease activity, prior therapy, demographics (e.g., women in their childbearing years), concomitant therapies, and presence of other serious conditions?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial.2016
Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial.2016
Long-Term Outcomes of Patients With Recent-Onset Rheumatoid Arthritis After 10 Years of Tight Controlled Treatment: A Randomized Trial.2016
Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study).2016
Impact of physicians' adherence to treat-to-target strategy on outcomes in early rheumatoid arthritis in the NEO-RACo trial.2015
The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression.2016
Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE).
Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.
Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): results from a randomized trial.2015
Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial.
Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period.
Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial.2015
Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis.2014
When to adjust therapy in patients with rheumatoid arthritis after initiation of etanercept plus methotrexate or methotrexate alone: findings from a randomized study (COMET).2014
Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study.2014
Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial.2015
Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial.
Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial.2014
Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study.2013
Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial.2014
A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial.2015
Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10-year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open-label extension.2014
Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial.2014
M-ficolin levels reflect disease activity and predict remission in early rheumatoid arthritis.2013
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).2014
Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial.2014
Biological vs. conventional combination treatment and work loss in early rheumatoid arthritis: a randomized trial.2013
A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study.2014
Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis: results from a two-year randomized, double-blind trial.2013
A non-inferiority trial of an attenuated combination strategy ('COBRA-light') compared to the original COBRA strategy: clinical results after 26 weeks.2014
Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial.2014
Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study.2014
Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated with methotrexate in a DAS-steered strategy.2013
Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in early rheumatoid arthritis: 2-year quality-of-life results of the randomised, controlled, SWEFOT trial.2013
Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate.2013
Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis.2012
Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study).
Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study.2013
Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial.
Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study.2012
Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study.2013
A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial.2012
Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial.2012
Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial.2012
Health-related quality of life outcomes of adalimumab for patients with early rheumatoid arthritis: results from a randomized multicenter study.2012
Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE.2012
Abatacept plus methotrexate provides incremental clinical benefits versus methotrexate alone in methotrexate-naive patients with early rheumatoid arthritis who achieve radiographic nonprogression.2011
Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes.2011
Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis?2012
Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate.2011
The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study.2011
Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study.2011
Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial.2011
Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER.2010
Safety and retention of combination triple disease-modifying anti-rheumatic drugs in new-onset rheumatoid arthritis.2015
Tumor necrosis factor α inhibitor use and decreased risk for incident coronary events in rheumatoid arthritis.2014
Baseline factors predicting change from the initial DMARD treatment during the first 2 years of rheumatoid arthritis: experience in the ERAN inception cohort.
Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with early RA.2012
Leflunomide in the treatment of patients with early rheumatoid arthritis--results of a prospective non-interventional study.2010
Treatment of early RA in clinical practice: a comparative study of two different DMARD/corticosteroid options.-- Not Found --
Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis.2010
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
Renal safety of initial combination versus single DMARD therapy in patients with early rheumatoid arthritis: an 11-year experience from the FIN-RACo Trial.-- Not Found --
Evaluation of hand bone loss by digital X-ray radiogrammetry as a complement to clinical and radiographic assessment in early rheumatoid arthritis: results from the SWEFOT trial.2013
Aiming at low disease activity in rheumatoid arthritis with initial combination therapy or initial monotherapy strategies: the BeSt study.-- Not Found --
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
Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study.2010
Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial.2010
Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis.2010
Changing sulphasalazine to methotrexate does not improve the 2-year outcomes of the initial single DMARD treatment in early rheumatoid arthritis: subanalysis of the FIN-RACo trial.2013
Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the optimized treatment algorithm in early RA (OPERA) trial.2017
Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial.2017
Infliximab Versus Conventional Combination Treatment and Seven-Year Work Loss in Early Rheumatoid Arthritis: Results of a Randomized Swedish Trial.2016
Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA).2016
Effect of adalimumab on the work-related outcomes scores in patients with early rheumatoid arthritis receiving methotrexate.2016
Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques.
Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.2016
Tapering conventional synthetic DMARDs in patients with early arthritis in sustained remission: 2-year follow-up of the tREACH trial.2016
Adherence to methotrexate in rheumatoid arthritis: a danish nationwide cohort study.2015
Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis.2006
A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.2000
Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.1997
The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.2006
Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis.2005
Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes.2002
Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial.
COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention.2002
Infliximab treatment maintains employability in patients with early rheumatoid arthritis.2006
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.2004
Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial.2005
Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial.2004
Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study.2004
Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study.2003
Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.1999
Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.1999
Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial.1997
Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis.2009
Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis.2008
Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis.
Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.2008
Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade.2009
Adalimumab plus methotrexate improved SF-36 scores and reduced the effect of rheumatoid arthritis (RA) on work activity for patients with early RA.2008
Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis.2008
Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial.2007
Probability of continued low disease activity in patients with recent onset rheumatoid arthritis treated according to the disease activity score.2008
The effect of etanercept on work productivity in patients with early active rheumatoid arthritis: results from the COMET study.
Methotrexate therapy in rheumatoid arthritis after failure to sulphasalazine: to switch or to add?2009
Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.2009
Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study.2009
Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors.2009
Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.2005
Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial.2017
Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial.2017
Best cost-effectiveness and worker productivity with initial triple DMARD therapy compared with methotrexate monotherapy in early rheumatoid arthritis: cost-utility analysis of the tREACH trial.2016
Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study.2017
Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?2017
Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial.2017
Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone.2007
Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis.2006
Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial.2009
Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis.2007
Janssen Response to Data Requested by the Agency for Healthcare Research and Quality on Drug Therapy for Early Rheumatoid Arthritis in Adults An Update
A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-nave Adults With Early Active Rheumatoid Arthritis (C-early)
Patient-reported outcomes in newly diagnosed early rheumatoid arthritis patients treated to target with a tocilizumab- or methotrexate-based strategy.2017

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