Adenosine and Adenosine Receptors in Rheumatoid Arthritis

Melissa Padovan; Fabrizio Vincenzi; Marcello Govoni; Alessandra Bortoluzzi; Pier Andrea Borea; Katia Varani


Int J Clin Rheumatol. 2013;8(1):13-25. 

In This Article

Treatment of RA

Currently, optimal management of RA is needed, within 3–6 months after the onset of disease, since a narrow 'window of opportunity' is considered to be suitable to achieve remission.[13] Early prognostic assessment in order to establish the risk of aggressive disease is crucial to guide the therapeutic approach. A good early response to treatment predicts better long-term response in the following 5 years.[14] There is increasing acceptance of paradigms of adjusting therapy to achieve a predefined goal, such as remission or low-disease activity ('treat to target') with frequent monitoring and strategy adjustments, and if necessary ('tight control'), until the target is reached.[15–17] The use of a composite measure of disease activity was recommended, such as the Disease Activity Score Assessing 28 Joints (DAS-28), the Simplified Disease Activity Index (SDAI) or the Clinical Disease Activity Index (CDAI).[18,19]

In recent decades, there was an inversion of the pyramid, with earlier and more intensive and innovative approach to RA treatment.[20,21] After a long time focused on the use of conventional disease-modifying antirheumatic drugs (DMARDs) alone or in combination, the advent of 'biologic' drugs, which are able to block the cytokine pathway and B- and/or T-cell activation, has profoundly changed the therapeutic scenario and, consequently, the current strategy adopted to cure RA.[10,22] Glucocorticoids have been, and continue to be, a part of the treatment strategy throughout the years.[23] The recent EULAR recommendations for the treatment of RA identify three phases of therapy.[15] Phase one is the initiation of DMARD treatment as monotherapy, immediately after diagnosis of RA. The recommended drug is methotrexate (MTX), widely seen as an anchor drug in RA.[24,25] Phase two is the escalation of therapy by switching to a different DMARD or to a combination therapy. If this approach fails to achieve the target of clinical remission (or low disease activity) within 3–6 months, and the patients have poor prognostic factors (high disease activity, early joint damage, high levels of RF or ACPA), the new escalation of therapy is the addition of a biologic drug, TNF blockers. However, to date, approximately one-third of patients treated with anti-TNF-α agents show an inadequate response or develop side effects requiring discontinuation of therapy.[26] Phase three is in case of anti-TNF failure or lack of efficacy and/or toxicity, the recommended approach is to change the biologic treatment by switching to an alternative TNF antagonist (in combination with a synthetic DMARD) or replacing the biologic treatment with an alternative with different target therapy (B-cell-targeted therapy, IL-6, CTLA-4 modulation).

Under this point of view, it is very important to identify predictive factors related to a better or poor response or to major risk of toxicity aimed to guide the therapeutic choice and faster adjust the therapeutic intervention.[17,26,27]