Elsevier

The Lancet

Volume 389, Issue 10086, 10–16 June 2017, Pages 2338-2348
The Lancet

Series
Novel treatment strategies in rheumatoid arthritis

https://doi.org/10.1016/S0140-6736(17)31491-5Get rights and content

Summary

New treatment strategies have substantially changed the course of rheumatoid arthritis. Many patients can achieve remission if the disease is recognised early and is treated promptly and continuously; however, some individuals do not respond adequately to treatment. Rapid diagnosis and a treat-to-target approach with tight monitoring and control, can increase the likelihood of remission in patients with rheumatoid arthritis. In this Series paper, we describe new insights into the management of rheumatoid arthritis with targeted therapy approaches using classic and novel medications, and outline the potential effects of precision medicine in this challenging disease. Articles are included that investigate the treat-to-target approach, which includes adding or de-escalating treatment. Rheumatoid arthritis treatment is impeded by delayed diagnosis, problematic access to specialists, and difficulties adhering to treat-to-target principles. Clinical management goals in rheumatoid arthritis include enabling rapid access to optimum diagnosis and care and the well informed use of multiple treatments approved for this disease.

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

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.

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