Editorial

Early rheumatoid arthritis: a medical emergency?

The improvement of rheumatoid arthritis (RA) management has been strictly related to methotrexate (MTX) long-term effectiveness, safety profile and its widespread use in clinical practice over the last decades. According to the results of several head-to-head comparative trials against other synthetic DMARDs, MTX has been recognised as the “anchor drug” for the treatment of RA at the end of the 1990s. The subsequent increasing knowledge in the area of RA pathophysiology has progressively expanded the arsenal of available therapeutic tools, especially by the introduction of novel drugs such as biological DMARDs. The introduction of therapies targeted to key molecules and cells involved in RA pathogenesis has significantly changed the strategies for disease management, possibly modifying the key role of MTX. This review first analyses data supporting the evolution of MTX towards the role of “anchor drug” for RA in the pre-biologic era. We will then examine how the introduction and progressive spreading of biological agents could have modified the central role of MTX in the approach to RA.

Arthritis is the most common cause of disability. Hence, prompt recognition and management of acute-onset polyarthritis are paramount to prevent progressive damage. When rheumatoid arthritis is considered as a prototypical example of polyarthritis, the stakes of early and accurate evaluation are evident. The challenge is in determining when undifferentiated polyarthritis ends and rheumatoid arthritis begins. This chapter reviews the evidence to help clinicians identify and manage patients who present with acute polyarticular inflammation.

The goal of juvenile idiopathic arthritis (JIA) treatment is to achieve remission of disease. The absence of a full understanding of the disease pathogenesis for JIA hinders the development of truly effective treatment approaches. Further, the lack of clear knowledge regarding the mechanisms of action of rheumatologic medications and the existence of few randomized controlled trials leaves clinicians with very little evidence upon which to base decisions regarding the best timing, dosages or combinations of medications to be used for fully effective treatment of JIA. There is now a shift in treatment focus from that of chasing failure (gradual add-on approach to the use of medications) to one of early aggressive combination treatment. This chapter will discuss the current approaches to medical management of JIA and the medications currently available for use. JIA treatment is a vast, rich area in need of research.

In this article, we will review B lymphocyte development and function, then discuss the role of B cells in RA, including immune complex formation; the K/BxN mouse model of RA; toll-like receptors; B cells as antigen presenting cells; germinal center-like structures in RA synovium; and influence on T cell activation, leukocyte infiltration, and angiogenesis. With regard to autoantibody production, we will focus on rheumatoid factor (RF) and anti-CCP antibodies, particularly mechanisms of their production; sensitivity and specificity in RA; and their roles as prognostic factors. Other autoantibodies will be discussed, as will treatment implications and future areas of investigation related to B cells and autoantibodies in RA.

Early diagnosis of rheumatoid arthritis (RA) is an important challenge for clinical rheumatologists. This is because there is substantial evidence that early treatment with disease-modifying antirheumatic drugs leads to a better disease outcome. The 1987 American College of Rheumatology classification criteria for RA do not perform well as a diagnostic tool in early arthritis. Therefore, diagnostic studies are needed to develop diagnostic criteria or prediction models that enable clinicians to distinguish RA from other arthritides in an early phase of the disease. Diagnostic studies are hampered by the lack of an independent gold standard for RA. Since the most important clinical features of RA are the persistence of the arthritis and the development of erosions, arthritis outcome is a clinically relevant gold standard. Diagnosis is a phased, multivariable process in which the probability of the presence of disease is updated continuously when new diagnostic information is added to the patient profile. Therefore, besides univariate studies, multivariable diagnostic studies are needed to evaluate the value of current diagnostic practice or to evaluate the added value of a new diagnostic procedure. This chapter describes univariate and multivariate studies that have been performed in early arthritis populations to assess the diagnostic value of medical history, physical examination, laboratory tests and imaging in RA diagnosis.

La nécessité de prendre en charge précocement une polyarthrite rhumatoïde (PR) débutante, en particulier quand il existe des facteurs de mauvais pronostic, est dorénavant admise. Dans la stratégie thérapeutique; l'existence d'une ⪡ fenêtre d'opportunité ⪢ pendant les deux premières années de la maladie doit permettre de bloquer le processus d'agression articulaire. Reste à savoir quelle est la stratégie optimale, en particulier quelle est la place de l'étanercept et des autres anti-TNF daps le traitement de la PR précoce par rapport au méthotrexate (MTX) et à des combinaisons médicamenteuses dites ⪡ intensives ⪢.

Les études randomisées COBRA, FIN-RACO, BeST et TICORA ont démontré l'efficacité de stratégies ⪡ intensives ⪢ associant d'emblée ou rapidement plusieurs traitements de fond conventionnels par rapport aux monothérapies. Néanmoins, l'efficacité de ces stratégies semble diminuer des que la pression médicamenteuse est réduite.

Les anti-TNF ont une efficacité remarquable dans la PR débutante. L'étude ERA (Early Rheumatoid Arthritis) a démontré une efficacité clinique et surtout structurale rapide de l'étanercept comparé au MTX dans des PR récentes actives et sévères. Cette efficacité se maintient pendant 5 ans avec un rapport bénéfice/risque au moins équivalent à celui du MTX. Ces données ont permis à l'étanercept d'obtenir l'AMM pour le traitement de la PR sévère, active et évolutive de l'adulte non précédemment traitée par le MTX. L'efficacité et la tolérance de l'infliximab ont également et́é démontrées, notamment dans l'étude ASPIRE, et l'évaluation de l'adalimumab dans la PR débutante est en tours.

Chez des patients avec une PR évoluant depuis quelques années mais non préalablement traitde par MTX, le bénéfice symptomatique structural de l'étanercept, associé au MTX, a également été démontré (étude TEMPO).

Quand on envisage un traitement précoce, il est possible qu'il soit prolongé, ce qui justifie un profil de tolerance au long tours acceptable. Les données a long terme sont assez rates mais le profil de tolérance à 5 ans est rassurant. Le risque infectieux et dysimmunitaire est assez bien identifié et les données concernant les cancers solides sont très rassurantes. Dans 1' état actuel des connaissances,l'excès de lymphome observé avec les différents anti-TNF ne pent pas être formellement lié aux anti-TNF, car ce risque existe dans tome PR active et sévère.

Au total, la confirmation des donndes d'efficacité et de tolérance favorables devrait inciter les rhumatologues à prescrire d'emblée un anti-TNF lorsque le pronostic évolutif du patient semble potentiellement sévère. Restera à bien définir la bonne stratégie d'utilisation de ces anti-TNF.