Elsevier

Autoimmunity Reviews

Volume 11, Issue 8, June 2012, Pages 589-592
Autoimmunity Reviews

Review
Early treatment in early undifferentiated arthritis

https://doi.org/10.1016/j.autrev.2011.10.019Get rights and content

Abstract

The early diagnosis of new-onset rheumatoid arthritis (RA) has become a major objective for rheumatologists in order to identify a management strategy able to change the natural history of the disease and to prevent joint damage and functional impairment. Emergent evidence emphasizes the benefits of early aggressive therapy of RA. By the nineties, early arthritis cohorts have been collected throughout the world with the aim to increase the early referral of patients with early onset disease by the general practitioners and to collect data on the development of full-blown RA. The frequency of undifferentiated arthritis (UA) ranged from 23% to 81% in these early cohorts with most of them reporting a rate of 30%. The transition rate from UA to RA was between 13% and 54%. A percentage of 20–60% of patients with UA had a self-limiting disease.

Our article deals with the controversy existing in the management of UA. Should every patient with UA be treated? Could patients with a favorable disease course be exposed to unnecessary risk with initiation of aggressive therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) or biologic agents? The pros and cons of treating patients with UA are examined.

Introduction

Rheumatoid arthritis (RA) is a chronic synovitis characterized by progressive joint damage, functional disability, and increased morbidity and mortality. The early diagnosis of recent-onset RA has become a main objective for rheumatologists with the intention to realize a management strategy able to modify the natural history of the disease and to avoid joint damage and functional impairment. Since the nineties, greatly efficient management strategies for RA have been set and it has become clearly apparent that these strategies should be put in operation in the early phases of the disease evolution [1]. Patients should start disease-modifying anti-rheumatic drugs (DMARDs) as soon as possible and those failing these drugs should be treated with a biologic agent. Early beginning of aggressive therapy in nascent RA has shown to be more successful in achieving true disease remission, inhibiting the radiographic progression of joint damage, and improving physical function and quality of life compared with deferred onset of treatment [2], [3], [4]. A meta-analysis of observational studies and randomized control trials showed that there is a critical period, a therapeutic window, during which anti-rheumatic therapy should be initiated to alter the long-term course of the disease [5].

The 1987 American College of Rheumatology (ACR) criteria [6] for the classification of RA proved not enough sensitive to recognize RA in the initial stages of disease evolution [7]. By the beginning of the nineties, early arthritis cohorts (EACs) have been collected in different early arthritis clinics worldwide with the aim to increase the early referral of patients with early onset disease by the general practitioners or primary care physicians and to collect data on the development of overt RA [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. New concepts were introduced: recent-onset RA not meeting the 1987 ACR classification criteria, early inflammatory arthritis (EIA) and undifferentiated arthritis (UA) [17]. Data collected by these cohorts permitted to build the 2010 ACR/EULAR (European League Against Rheumatism) classification criteria for RA at an early stage [18] which have shown good diagnostic properties in validation studies [19]. The epidemiological data from these EACs were recently reviewed by Hazes and Luime [17]. No consensus exists in these early arthritis cohorts on the definition of EIA and UA regarding the duration of the disease, number of involved joints and the role of additional factors such as the level of acute-phase reactants. Therefore, the frequency of UA ranges in these early cohort studies from 23% to 81% with most of them reporting a rate around 30%. Different data also exist on the transition rate from UA to RA with values varying from 13% to 54%. A percentage ranging from 21% to 87% had UA at the end of follow-up. In addition, 20–60% of patients showed a self-limiting disease. As far as predictors of persistent (as opposed to remission) and erosive disease are concerned, a combination of simply accessible clinical and serologic data has been identified [17]. Among these, the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), usually determined by assays for antibodies against cyclic citrullinated peptide (anti-CCP), are constant important determinants. Some models for predicting RA development have also been suggested [17].

Our article deals with controversies existing in the management of UA. Should every patient with UA be treated? Could patients with a favorable disease course be exposed to unnecessary risk with initiation of DMARD or biologic therapy? The pros and cons of treating patients with UA are examined.

Section snippets

PROS

Management of UA remains a major challenge in rheumatology clinical practice. Although by this diagnosis we generically mean any form of inflammatory arthritis that cannot be classified into a definite rheumatic disorder after initial assessment, UA actually spans a wide spectrum of heterogeneous conditions with varied natural courses. Alongside benign, self-limiting forms, a significant proportion of patients with UA will experience disease persistency with up to one-third developing overt RA

CONS

RA is long-lasting, causes structural joint damage, and adversely affects physical function and social life. However, many studies have shown that early optimal treatment can limit its impact and keep patients at work [17], [33], [34]. Furthermore, there is new evidence that inducing early remission can interfere with the disease process and radiographic damage. In the early 1980s, RA affected ~ 1% of the population worldwide and was associated with many clinical problems but, although still far

Conclusions

Future studies should contribute to solve the controversies existing on the management of UA. Firstly, an agreement should be reached on the definition of IA and UA. So far, a lot of dissimilar definitions are used in the ongoing EACs [17]. To increase the compatibility of EACs, Hazes and Luime suggest to utilize robust (all inclusive) criteria that permit the inclusion of a wide spectrum of patients with EIA at inception, and more restricted inclusion criteria at an advanced stage [17]. They

Take-home messages

  • Evidence has been gathered on the clinical and radiographic benefits of early aggressive therapy of RA.

  • ACR/EULAR classification criteria for RA at an early stage have recently been published.

  • Up to 50% of patients with UA will develop RA while in the remaining patients the disease usually shows a self-limiting course.

  • Early treatment pros: UA can currently be regarded as the best interval during which outcomes are more likely to be modulated by targeted interventions. Based on the safety profile

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