ANTI-RO/SS-A ANTIBODY IS AN INDEPENDENT FACTOR OF INSUFFICIENT RESPONSE TO ANTI-TNF-ALPHA MONOCLONAL ANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Anti-Ro/SS-A antibody (anti-Ro) is frequently detected in rheumatoid arthritis (RA), and patients with RA are often complicated with Sjögren's syndrome (SjS). SjS is thought to be one of the poor prognostic conditions of RA. In addition, we reported that anti-tumor necrosis factor (TNF)-alpha inhibitors were less effective in anti-Ro-positive RA patients and the presence of anti-Ro could be a factor for poor response to TNF-alpha inhibitors in last EULAR meeting. Objectives: To study the difference in clinical responses between anti-Ro positive and negative RA patients treated with infliximab (IFX), adalimumab (ADM), etanercept (ETN) and tocilizmab (TCZ). Methods: Anti-Ro and anti-cyclic citrullinated peptide antibody (ACPA) were measured using DID and ELISA, respectively, in 166 patients with RA. Clinical response according to the disease activity score 28 (DAS28) EULAR response criteria at 24 and 54 weeks was compared between anti-Ro-positive and -negative patients with RA. Factors for poor response to the biologics, including anti-Ro, ACPA, presence of SjS and DAS28 before commencement of the biologics, were estimated for each biologics by univariate- and multivariate-logistic regression analysis. Results: The 166 patients treated with IFX, ETN, ADM, and TCZ (100, 53, 12 and 1, respectively) as first biologics, were examined. Among these patents, the first biologics were switched to ETN (19), ADM (5) and TCZ (9). Anti-Ro was detected in 32 of 166 patients (19.3%) and 17 patients were complicated with SjS. The frequency of anti-Ro was comparable among the patients treated with each biologics (IFX 20.0%, ETN 18.9%, ADM 16.7%, and TCZ 0%, respectively). ACPA was detected in 151 patients (90.9%) and the frequency of ACPA was significantly higher in anti-Ro-positive group (100%) than that in negative group (88.8%, P<0.05). IFX and ADM were discontinued more frequently due to the lack of efficacy in anti-Ro-positive group compared with -negative group at 54 weeks (54.5% and 26.7%, respectively, P=0.012). Moreover, in anti-Ro-positive patients, the discontinuation rate was significantly higher in the IFX or ADM treated group than that in the ETN or TCZ treated group (54.5% and 10.0%, respectively, p=0.019), while there was no difference among the groups in anti-Ro -negative patients. Furthermore, all anti-Ro-positive patients, who responded insufficiently to IFX (9) or ADM (2), showed clinical response (moderate: 7, good: 4) after switching to ETN (7) or TCZ (4). The logistic regression analysis showed that anti-Ro was an independent factor for the poor response to the biologics both in the univariate model (OR 3.08, 95%CI 1.36–6.97) and in the multivariate models (OR 3.29, 95%CI 1.08–10.07). Moreover, anti-Ro antibody was a strong prognostic factor especially for the discontinuation of IFX and ADM (univariate analysis: OR 12.0, 95%CI 3.62–39.73, multivariate analysis: OR 11.1, 95%CI 2.74-49.09). Conclusion: The presence of anti-Ro might be related to the lack of clinical efficacy in patients with RA treated with biologic agents, especially with the anti-TNF-alpha monoclonal antibodies, IFX and ADM. This result indicates that ETN is more promising in treating the patients with anti-Ro-positive RA as first biologics. Disclosure of Interest: None declaredCitation: Annals of the Rheumatic Diseases, volume 69, supplement 3, year 2010, page 209Session: Rheumatoid arthritis – anti-TNF therapy (Poster Presentations )