We searched MEDLINE and PubMed for articles published in English from Jan 1, 2000, to May 29, 2017, using the terms (early) “rheumatoid arthritis” in conjunction with (early) “diagnosis”, “treatment”, “strategies”. Articles were selected on the basis of our personal judgment of their relevance within the scope of this Series paper.
SeriesNovel treatment strategies in rheumatoid arthritis
Introduction
Until the 1990s, the diagnosis of rheumatoid arthritis had devastating consequences, which usually led to progressive joint destruction, reduced life expectancy, early unemployment, and considerable disability.1 Treatment included the pyramid approach, which started with bed rest, non-steroidal anti-inflammatory drugs, and the addition of effective disease-modifying anti-rheumatic drug (DMARD) therapy following disease progression.2 The first paper in this Series,3 outlined the pathophysiology of rheumatoid arthritis learned from use of biologics and small molecule inhibitors in rheumatoid arthritis, and this paper will focus on novel treatment concepts that substantially alter the disease course of the condition, including treatment of early disease with classic DMARD medication often in combination, and recently introduced drugs.
Today, the aim of treatment in any disease state is to achieve remission, or low disease activity if remission is not possible because of long-standing disease or comorbidities. Treatment should aim to avoid joint damage and disability, as well as systemic manifestations, such as cardiovascular damage, which is best achieved by a treat-to-target approach that includes tight disease control. Non-pharmacological treatments, such as physical and occupational therapy, patient counselling with regard to lifestyle changes (eg, smoking cessation, attaining ideal bodyweight, exercise, and drug adherence) and surgical approaches, are important treatment resources if conservative treatments, such as drug therapy, physical therapy, and non-surgical interventions, have failed, but are beyond the scope of this Series.
Section snippets
Early recognition: the window of opportunity
The onset of rheumatoid arthritis is usually insidious with patients presenting with only one or a small number of swollen joints, morning stiffness, and non-specific constitutional symptoms, including fatigue and a flu-like feeling. Joint involvement in early rheumatoid arthritis might be asymmetric and not polyarticular. Only in later stages of the disease does the typical symmetric polyarthritis evolve.4 Thus, the immediate recognition of rheumatoid arthritis represents a challenge for
Treatment recommendations
Treating to a target can vary depending on the treatment goals of the patient and physician and according to which individualised outcomes can be achieved. The outcome targets might vary (ie, remission, low disease activity) and might also include prevention of joint damage, disability, reduction of mortality, and cardiovascular events.13 In active rheumatoid arthritis, rapid achievement of tight control of disease activity is required with frequent assessments of the patient and modification
JAK inhibitors
Many rheumatoid arthritis trials with novel oral small molecules have been ineffective. The mitogen-activated protein kinase pathway seemed important in rheumatoid arthritis but trials of agents targeting this pathway were negative.57, 58 By contrast, medications that inhibit the JAK pathways have led to a considerable breakthrough in rheumatoid arthritis treatment. Although efficacy could be anticipated because of the numerous cytokines that use JAK pathways for intracellular signalling,
Prevention of rheumatoid arthritis
The concept of pre-rheumatoid arthritis has evolved.90 This concept can be applied to patients who do not meet criteria for rheumatoid arthritis but have features, such as some swollen joints, or others who are anti-citrullinated protein antibodies positive and have arthralgia. Patients with undifferentiated inflammatory arthritis who do not meet criteria for rheumatoid arthritis6 have been studied in trials comparing treatment with no treatment to prevent the onset of rheumatoid arthritis,
Comorbidities and mortality
Patients with rheumatoid arthritis (both established and early) have a higher burden of cardiovascular disease and cardiovascular risk factors such as hypertension, diabetes, obesity, hyperlipidaemia, and smoking.104, 105 The incidence of infections and lymphoproliferative cancers are increased in patients with rheumatoid arthritis compared with the general population.106 Patients with the disease also have a higher incidence of lung disease (obstructive and restrictive) and are more likely to
Conclusion and perspectives
Several strategies and accompanying recommendations can facilitate optimal care for patients with rheumatoid arthritis with a better prognosis than that observed historically. The most important aspects of rheumatoid arthritis management are the early diagnosis of patients, prompt initiation of DMARD therapy, and regularly assessing patients to achieve a target of remission or low disease state. This management strategy will result in favourable outcomes for most patients.
Search strategy and selection criteria
References (114)
- et al.
Pathogenetic insights from the treatment of rheumatoid arthritis
Lancet
(2017) - et al.
Are early arthritis clinics necessary?
Best Pract Res Clin Rheumatol
(2005) - et al.
Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial
Lancet
(2013) - et al.
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 randomized trial
Lancet
(2009) - et al.
Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multi-centre, randomised, double-blind, double-dummy, strategy trial
Lancet
(2016) - et al.
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
Lancet
(2008) - et al.
Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomized controlled OPTIMA trial
Lancet
(2014) - et al.
Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study
Lancet
(2016) Janus kinase inhibitors for rheumatoid arthritis
Curr Opin Chem Biol
(2016)- et al.
Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial
Lancet
(2013)
Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial
Lancet
Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database
Ann Rheum Dis
Primer on the rheumatic diseases
Rheumatoid arthritis—clinical features
2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative
Ann Rheum Dis
What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review
Ann Rheum Dis
Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts
Ann Rheum Dis
Equivalent responses to disease-modifying antirheumatic drugs initiated at any time during the first 15 months after symptom onset in patients with seropositive rheumatoid arthritis
J Rheumatol
2016 update of the EULAR recommendations for the management of early arthritis
Ann Rheum Dis
Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial
BMJ
Tightening up? Impact of musculoskeletal ultrasound disease activity assessment on early rheumatoid arthritis patients treated using a treat to target strategy
Arthritis Care Res
Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force
Ann Rheum Dis
Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis
Ann Rheum Dis
2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis
Arthritis Care Res
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
Ann Rheum Dis
Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update
Ann Rheum Dis
Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial
Ann Rheum Dis
Baricitinib versus placebo or adalimumab in rheumatoid arthritis
N Engl J Med
Comparative efficacy of novel DMARDs as monotherapy and in combination with methotrexate in rheumatoid arthritis patients with inadequate response to conventional DMARDs: a network meta-analysis
J Manag Care Spec Pharm
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
Arthritis Rheum
Therapies for active rheumatid arthritis after methotrexate failure
N Engl J Med
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
Ann Rheum Dis
Predictors for remission in rheumatoid arthritis patients: a systematic review
Arthritis Care Res
Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data
BMJ
Discontinuation of biologics in patients with rheumatoid arthritis
Clin Exp Rheumatol
Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: a network meta-analysis
Cochrane Database Syst Rev
Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis
BMJ
Tofacitinib versus methotrexate in rheumatoid arthritis
N Engl J Med
Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment
Arthritis Rheumatol
Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomized controlled trial
Ann Rheum Dis
Active-controlled study of patients receiving infliximab for the treatment of rheumatoid arthritis of early onset study group. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial
Arthritis Rheum
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
Arthritis Rheum
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
Ann Rheum Dis
Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis
Arthritis Rheum
Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors
Ann Rheum Dis
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
Ann Rheum Dis
Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial
Ann Rheum Dis
American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis
Arthritis Rheum
Cited by (725)
Reasons for multiple biologic and targeted synthetic DMARD switching and characteristics of treatment refractory rheumatoid arthritis
2024, Seminars in Arthritis and RheumatismAbelmoschus manihot (L.) medik. seeds alleviate rheumatoid arthritis by modulating JAK2/STAT3 signaling pathway
2024, Journal of EthnopharmacologyA review of hyaluronic acid-based therapeutics for the treatment and management of arthritis
2024, International Journal of Biological MacromoleculesXuetongsu attenuates bone destruction in collagen-induced arthritis mice by inhibiting osteoclast differentiation and promoting osteoclast apoptosis
2024, International Journal of Biochemistry and Cell Biology