BackgroundUp to one third of spondylarthritis (SpA) fail to respond to anti-TNF agents or experience drug toxicity leading to treatment withdrawal. Part of the treatment failure can be explained by the development of anti-drug antibodies (ADA).ObjectivesTo evaluate the relation between immunogenicity, drug levels and clinical efficacy of TNF inhibitors (TNF-i) in ankylosing spondylitis (AS).MethodsWe performed a prospective observational study in a cohort of 47 consecutive AS patients receiving adalimumab (ADL) (13; 27.7%), infliximab (IFX) (13; 27.7%) or etanercept (ETN) (21; 44.7%). DiseaseDisease activity (BASDAI, ASDAS), outcomes and adverse events were evaluated at baseline and study visit, while serum TNF-i and ADA levels collected as a single-point data in both bio-naïve (37, 78.7%) and bio-experimented patients. Serum drug levels were considered positive for IFX if >0.035 μg/mL, for ADL >0.024 μg/mL and for ETN >0.035 μg/mL, while the cut-off value for the ADA positivity to IFX was established at 5AU/ml, for ADL at 10AU/mL and ETN at 142 AU/mL (ELISA, Progenika).Statistical analysis was performed using SSPS version 19.0, p<0.05ResultsAt baseline mean BASDAI was 7.69 and mean ASDAS-CRP 3.50, with no difference in disease activity between patients who did or did not later develop ADA (p<0.05). 37 (78.7%) AS were BASDAI responders at study visit (BASDAI 1.16, ASDAS-CRP 1.73).ADA were detected in 8/47 (17%) and were more frequent in patients treated with ADL (5 cases; 38.5%) vs IFX (3 cases; 23.1%); no with ETN. Both ADL and IFX levels were significantly higher for ADA negative than for ADA positive patients (ADL: 3.92μg/mL vs 0.02μg/mL, p<0.01; IFX: 1.82μg/mL vs 0.03 μg/mL, p<0.01).A significant association between clinical activity (ASDAS) and immunogenicity (ADA status) was reported: patients who had developed ADA had higher disease activity (3.10 vs 1.73, p<0.01), and more patients were classified as being in a high or very high disease activity status.Furthermore, a relation between clinical improvement (change in ASDAS) and immunogenicity was reported: ADA-positive AS achieved worse clinical response than ADA-negative cases, with a significant association between ADL respectively IFX levels and ASDAS (p<0.05).ConclusionsADL and IFX levels are commonly influenced by ADA-positivity, and related to clinical response in AS, suggesting that therapeutic drug monitoring should be investigated as a possible tool to optimise treatment such patients.ReferencesArstikyte I et al. Influence of Immunogenicity on the Efficacy of Long-Term Treatment with TNFα Blockers in Rheumatoid Arthritis and Spondyloarthritis Patients. BioMed Research International 2015Hoxha A, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: A prospective multicentre study. Joint Bone Spine 2015Disclosure of InterestNone declared

Objectives. To identify predictors for Simplified Disease Activity Index (SDAI) remission in patients with established rheumatoid arthritis (RA) under 12 months of anti-TNF therapy combined with synthetic disease modyfing antirheumatic drugs (sDMARD). Methods. We performed a prospective observational study in 90 RA patients with a high active disease refractory to sDMARDs, starting anti-TNFs. Patients were assessed every 3 months based on a well-defined protocol, including individual parameters (clinical, inflammatory) and composite tools (simplified disease activity index SDAI, functional index HAQ-DI); total and IgA-isotype rheumatoid factor (RF) as well as anti-citrullinated peptide antibodies (ACPAs) were measured at baseline, 6 and 12 months. Therapeutic response was evaluated according to EULAR criteria. The primary endpoint was SDAI remission (≤ 3.3) at 12 months of treatment. Univariate and multivariate logistic regression analysis (Forward LR method) were used to assess the manner and intensity in which several parameters (demographics, disease-related, labs and medication) power SDAI remission. Results. SDAI remission was reported in 39.7% cases. We identified nine relevant predictors for SDAI remission at 12 months of therapy by univariate analysis, including: age ≤ 50 years, disease onset ≤ 5 years, RA stages I and II, functional capacity stages I and II, HAQ-DI ≤ 2, concomitent sDMARD, baseline CRP ≤ 20 mg/l, IgA-RF ≤ 20 IU/ml and ACPAs ≤ 40 IU/ml. A mathematical model was further generated, based only on six out of nine parameters: age, disease stage, functional capacity, concomitent sDMARDs, CRP and ACPA. This model expresses a solid approximation for the analysed casess (the Hosmer-Lemeshow test λ² = 0.931, p = 0.920 ≥ 0.05, Cox and Snell R2 0.399). Finally, three significant factors were recognized (age under 50, disease stages I and II, ACPA levels ≤ 40 IU/ml), predicting SDAI remission with an overall constant precision of 83.3%. However, no significant impact on SDAI remission prediction was reported when adding other parameters to the above mentioned model. Conclusion. SDAI remission can be predicted in established RA patients using three major predictors, including age ≤ 50 years, disease stages I and II and baseline ACPA levels ≤ 40 IU/ml.

Background treat-to-target and tight control strategies are actually the two main paradigms in the treatment of rheumatoid arthritis (RA), aiming to improve patients outcome by achieving either remission or minimal disease activity status. There is actually no consensus regarding the right assessment tools for monitoring the magnitude of improvement and the absolute reached level in routine clinical practice. Objectives to compare EULAR-DAS28 with RAPID3 (a patient-reported outcome based on pain, patient global assessment of disease activity, and multidimensional HAQ)response criteria in patients with moderate to severe active RA treated with rituximab (RTX). Methods prospective observational study on 72 moderate to severe active RA (DAS28>3.2) receiving one cycle of RTX (two infusions of 1000 mg at two weeks interval). Response to treatment was appreciated at six months by: (i) EULAR-DAS28 response criteria, classified as EULAR good (decrease with 1.2 units), moderate (decrease of 0.6–1.2 units) or non-responder (decrease ≤0.6 units); and (ii) RAPID3 response categories defined as good (decrease with 3.6 units), moderate (decrease of 1.8–3.6 units) and poor (decrease ≤1.8 units). Statistical analysis was done in SPSS.16 (weighted kappa statistics, p<0.05. Results up to 85% of RA has been classified as good and moderate responders based on RAPID3, while about 75% have been responders according to EULAR-DAS28; moreover, nearly 45% of the RAPID3 good responders have also been categorized as moderate EULAR-DAS28 responders. Statistical significant moderate agreement between the EULAR-DAS28 response criteria and RAPID3 has been demonstrated (p<0.05). Conclusions Patient-centered tools such as RAPID3 allow more easily and quickly to quantify disease activity levels and patient responses to therapy, providing a more complex insight into the patient’s perception of disease status. Disclosure of Interest None Declared

Objective. To identify predictors for Simplified Disease Activity Index (SDAI) remission in established rheumatoid arthritis (RA) and to develop a predictive score for remission. Methods. Prospective 12-month observational study in ninety active RA receiving their first TNF-α inhibitor. Standard assessments consisted of disease activity scores (DAS28-ESR, SDAI) and immune parameters (total rheumatoid factor, RF; IGA-RF; anti-cyclic citrullinated peptide antibodies, ACPA). The primary outcome measure was SDAI remission (≤ 3.3) at 12 months. Univariate and multivariate logistic regression models were used to estimate association between baseline variables and SDAI remission. Results. 39.7% RA achieved remission, while 56.8% low disease activity. Significant association between SDAI remission and RA-onset before 50 (p = 0.000), history <5 years (p = 0.000), stage (p = 0.000), class I and II Steinbroker functional status (p = 0.022), HAQ-DI≤2 (p = 0.034), CRP ≤ 20mg/l (p = 0.041), IgA-RF ≤ 20 IU/ml (p = 0.002), ACPA ≤ 40 IU/ml (p = 0.047), concomitant DMARDs (p = 0.003) were identified. Four parameters independently predicted 12-month remission (age at onset under 50, RA duration <5 years, ACPA≤40 IU/ml, IgA-RF ≤ 20 IU/ml) as demonstrated by multivariate logistic regression (p<0.05), making correct prediction in 84.4% patients. Furthermore, the remission score correctly classified 90.6% RA, while the transformed simplified version up to 89.4% cases. Gender, clinical parameters and ESR were not predictors for treatment response (p > 0.05). Conclusion. SDAI remission can be predicted in established RA using a score based on age at onset, disease duration, titers of ACPA and RF isotype A. Such a simplified score may help clinicians to manage remission in RA patients according to the current treatment guidelines.

Background Although immune-mediated rheumatic disorders, particularly systemic lupus (SLE), are commonly associated with increased cardio-vascular risk (CVR), there are still controversies about the advantage of traditional scores such as SCORE and Framingham for CVR stratification in such patient population. Objectives To identify the ideal score for the stratification of CVR in patients with SLE. Methods Prospective observational study on 72 consecutive SLE patients (1987 ACR diagnostic criteria) (68 women, mean age of 48±13.8 years) who were evaluated based on a predefined protocol including disease activity and damage parameters (SELENA-SLEDAI, BILAG), traditional (diabetes mellitus, obesity, arterial hypertension, smoking, dyslipidemia) and non-traditional cardio-vascular risk factors (hsCRP and homocysteine level), and classic CVR scores (Framingham, SCORE). Statistics was done in SPSS-17, p<0.05%, patients being analyzed according to the presence of ischemic cardio-vascular events (stable angina, coronary artery disease). Results Although more than half (51.4%) of cases had no CVR (Framingham, SCORE), we have demonstrated increased CVR in patients with preexistent cardio-vascular events (21%), SCORE risk featuring a higher prediction level than Framingham. On the other hand, both hsCRP and homocysteine levels highly correlated with CVR scores, displaying predictive role for coronary artery disease, mainly in active disease subset. Conclusions A novel algorithm for the evaluation and CVR stratification in patients, considering both classic and inflammatory parameters, is mandatory. Disclosure of Interest None Declared