Marcello Govoni

Body weight, gender and response to TNF-α blockers in axial spondyloarthritis

OBJECTIVEnThe objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA.nnnMETHODSnOne hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30). After 12 months of treatment a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point and BASDAI ≤ 1 was the secondary end point.nnnRESULTSnAfter 12 months of anti-TNF treatment, 67.8% of men and 46.2% of women reached the BASDAI50 (P = 0.01). According to BMI categories, the rate of BASDAI50 achievement decreased from 72.8% in normal weight subjects to 54.5% in overweight and 30.4% in obese subjects (P < 0.001). In the logistic regression analysis, the best independent predictors of failure to obtain a BASDAI50 response at the 12th month of therapy in axial SpA patients were female gender [odds ratio (OR) 3.23 (95% CI 1.52, 7.14)] and a BMI ≥ 30 [OR 3.57 (95% CI 1.15, 11.11)]. Analysing outcomes based on IFX therapy (the larger subgroup), the BASDAI50 response rate fell from 79.0% in normal weight subjects to 56.7% in overweight and 16.7% in obese subjects (P < 0.001). No significant differences were observed with ADA and ETA.nnnCONCLUSIONnData suggest that being female, overweight and mostly obese is associated with a lower rate of success in obtaining response status in axial SpA patients treated with anti-TNF drugs. Body weight could represent a modifiable factor to reach the best outcome in axial SpA patients treated with TNF blockers.

FRI0384 Usefulness of Brain MRI in Early Lupus: How the Morphological Imaging Changes at Onset of the Disease and After Follow-Up

Background The prevalence of neuroimaging abnormalities is not defined in newly-diagnosed Systemic Lupus Erythematosus (SLE), especially in those patients without overt neuropsychiatric (NP) symptoms; furthermore the clinical significance of these alterations is not clear at all. Objectives To assess the prevalence of brain abnormalities found by Magnetic Resonance Imaging (MRI) in a monocentric cohort of patients with early SLE onset (within 12 months from diagnosis) with (NP-SLE) or without NP manifestations (SLE) and to assess if early abnormal neuroimaging findings could have a predictive role for lesion load progression or the occurrence of subsequent NP events. Methods We selected SLE patients, less than 55 years, diagnosed according to the 1997 ACR criteria, who underwent brain MRI examinations within 12 months since diagnosis and then repeated it in the following 24-36 months. Brain MRI results were considered as absence or presence of white matter hyperintensities (scoring 0-3 if focal lesions were respectively none, 1, 2-4 or >5) and also as absence or presence of atrophy (scoring 0-3 if atrophy was absent, light, moderate or severe) according to a modified semiquantitative scoring system proposed by Petri et al. Then we evaluated the appearance of each new NP event along a median follow up period of 42 months. Results We retrospectively evaluated 752 patients referred consecutively at our clinic dedicated to SLE in a period of 20 years (between 1995 and 2014); 46 patients met the criteria for inclusion in the study. The mean age of the whole studied population was 34 years (14-55 yrs), 93.5% female. Of these patients, 28 had at least 1 NP event at time of diagnosis (61%). Overall an abnormal MRI was reported in 21 patients (46%), especially in those with NP involvement (18 NP-SLE and 3 SLE, p=0,0023). At baseline median atrophy score and WMHI score were 0,15 and 1,02 respectively. After the first NP event all patients either increased their immunosuppressive therapy (steroid and/or cyclophosphamyde bolus) or added aspirin low dose or anticoagulant drugs. At the time of the second MRI, a lesion load progression or worsening was seen in 26% (12): 29% (8) of NPSLE and 22% (4) of SLE pts (p>0,05); in all SLE patients the first MRI was negative. Total and median (1,2) WMHI score worsened during FU, median score for atrophy doubled (0,28). Almost all (92%) worsened MRI were associated with positivity of antiphospholipid antibodies. Comparing patients with unchanged MRI to those with worsened MRI a new NP event was recorded in 5 pts versus 6 pts (p=0,02), for a total of 11 new NP episodes. Conclusions Imaging abnormalities are present in a high percentage of SLE individuals at onset of disease (46%). A basal neuroimaging evaluation in young patients with newly diagnosed SLE is recommended especially because the evolution of the neuroradiological pictures seems to be independent of the previous history. Serial assessment is extremely useful to compare with any further imaging finding. Although a predictive value for abnormal neuroimaging in new appearance of NP event has yet to be demonstrated we found that MRI worsening could predict the occurrence of new NP event during follow up. Disclosure of Interest None declared

SAT0156 Exposition to biological therapy during pregnancy: a single-centre study of pregnancy outcome in mothers with rheumatic diseases

Background Biologic DMARDs fall within the FDA category B or C. However many case series and registry data are available about women exposed during pregnancy. Objectives to extend information on this topic by the contribution of a tertiary single centre case series Methods Data were collected from a single-centre cohort of outpatients followed between 2006 and 2016. Women with rheumatic diseases (RD) exposed to biological (BE) agent during pregnancy or in the 3 months before conception were included. Outcomes in the BE group were compared with an age-matched group of pregnant women with RD non-exposed to biological agent (NE). Demographic and clinical data,obstetric outcome and neonatal complications were recorded. Results 34 pregnancies in 28 patients were included: 14 Rheumatoid Arthritis (RA), 6 ankylosing spondylitis (AS), 2 Psoriatic arthritis (PsA), 4 Undifferentiated spondyloarthritis (uSpA), 1 Dermatomyositis (DM), 1 Adult Onset Stills disease (AOSD); all were exposed to a biologic agent: 16 Etanercept (ETA), 7 Adalimumab (ADA), 4 Infliximab (IFX), 1 Certolizumab (CTZ), 5 Rituximab (RTX), 1 Anakinra (ANK). Median age was 34 yrs (range 24–50). All patients treated with TNFi and ANK withdrew therapy in early pregnancy (<10 weeks gestational age). 2 RA patients had 2 pregnancies each, during ETA treatment. A RA woman became pregnant 4 times during RTX therapy. 10 patients were also on csDMARDs therapy at the time of conceptions: 7 Hydroxycloroquine (HCQ),1 HCQ + Sulphasalazine (SSZ), 1 Cyclosporine A (CYA), which was continued, and 1 with Methotrexate which was immediately withdrawn. 1 RA patient started SSZ from the 24th week. 15 patients (7 RA, 2 PsA, 2 AS, 2 uSpA, 1 DM) started or increased oral and/or intra-articular steroids because of disease flare. A control group of 45 pregnancies observed in 42 patients not exposed to biologics was selected=“selected” (19 RA, 12 uSpA, 3 Juvenile Idiopatic Arthritis (JIA), 5 PsA, 1 AS, 1 DM, 1 AOSD), median age 35 (range 22–42). 18 patients were treated with csDMARDs during pregnancy (8 HCQ; 4 SSZ; 2 CYA+HCQ; 4 SSZ+HCQ). No other drugs were taken at the time of conception, apart from low dose of steroids in 24 cases; in 1 case intra-articular steroids were given because of disease flare. Pregnancy outcomes are summarized in tab.1: therapeutic abortions were performed for an extrauterine pregnancy occurred twice in the patient with RA who became pregnant 4 times during RTX treatment, after the 5th and the 6th retreatment. After the 4th retreatment she had an early spontaneous abortion. Previously, she delivered 2 healthy children after exposure to ETA and 3 treatment cycles of RTX. No serious perinatal complication occurred, excluding very preterm baby delivery at 28th weeks, who needed neonatal intensive care. No congenital malformations were observed. Klinefelter syndrome was diagnosed in 1 case. Conclusions In our case series no significant differences did occur in pregnancy outcome between BE and NE group, according to the most recent data published in literature. Additional data from larger numbers of pregnacy exposed to biological agents are required. Disclosure of Interest None declared

FRI0385 UCTD and Progression to SLE. Analysis of a Wide Monocentric Cohort with a Long Follow-Up

Background The term undifferentiated connective tissue diseases (UCTD) has been widely used to identify conditions not fulfilling classification criteria for a defined connective tissue diseases (CTD). Recently the introduction of new classification criteria for different CTD allowed to take a significant step forward for their early identification and for a more reliable diagnosis of UCTD. Objectives To analyze the clinical and serological characteristics of a large cohort of patients (pts) with UCTD and to evaluate: the incidence of Systemic Lupus Erythematosus (SLE) defined according two different “set” of classification criteria for lupus, ACR 1997 and SLICC 2012, in a time frame of 15 years (1999-2013); to analyse clinical and serological data comparing pts affected by stable UCTD to UCTD evolved to SLE. Methods A cohort of pts referred to our clinic dedicated to UCTD, who met the classification criteria proposed by Mosca et al. [1], were retrospectively analyzed. The pts with a median follow-up less than one year were excluded. Clinical and serological assessment was performed at the time of diagnosis (T0) and at 3 different time points indicated as T1 (time interval between the first and third year), T2 (between the third and fifth year) and T3 (from the fifth to the tenth year). The classification criteria for SLE, ACR 1997 and SLICC 2012, were applied to each patient at time T0, T1, T2 and T3. Results 329 pts were enrolled. An observation period up to T1 was recorded for the entire sample, up to T2 for 273 pts and 206 pts had completed the follow-up to T3. At T0 no pts met SLE/ACR criteria (according to inclusion criteria of study), whilst 44 pts met SLE/SLICC criteria: 41 females (F, 93.2%) and 3 males (M), mean age 40.1±14 years. Overall, at the end of the observation period, the SLE/SLICC criteria were cumulatively observed in 67 pts (20.4%), while 14 pts met the ACR criteria. In 12 pts both sets of criteria were satisfied. At the end of follow-up, 260 pts did not meet any set of classification criteria (UCTD stable, 79% of the whole population, 253 F and 7 M, mean age 53.6±15.5 years). During the follow-up the rate of progression to SLE was stable over the years, with a number of switch to SLE constant even after 5 years of diagnosis of UCTD. A peak rate of new cases was observed at T3 where five new cases of SLE/ACR (2.4%) and 7 cases of SLE/SLICC (3.4%) were recorded. The baseline clinical and serological characteristics of pts with stable UCTD were compared to pts evolved in SLE. Acute or subacute skin rash (p 0.02), serositis (p 0.03) and the presence of antiphospholipid antibodies (p 0.02) were the variables correlated with the progression to SLE/SLICC. Acute or subacute skin rash (p 0.001) and the presence of antiphospholipid antibodies (p 0.03) were the variables correlated with the evolution to SLE/ACR. Conclusions From our study in a cohort of UCTD pts the application of the new set of SLICC classification criteria for SLE, compared with the old ACR criteria, would not seem to have contributed significantly in terms of predictability of the evolution towards lupus, but certainly they expanded the number of pts classified as SLE at onset of the disease allowing a certain diagnosis in a greater number of pts who would otherwise be classified as UCTD. References Mosca M et al. Clin Exp Rheumatol 1999;17:615-620. Disclosure of Interest None declared

SAT0310 Overlap Syndrome Systemic Sclerosis-Rheumatoid Arthritis and Pulmonary Involvement: Description of A Monocentric Series

Background the overlap syndrome Systemic sclerosis-rheumatoid arthritis (SSc-RA) is characterized by the presence in the same patient of clinical and laboratory features that meet the classification criteria for both diseases. The current literature shows how that lung involvement is more frequent and severe in SSc-RA than in SSc alone [1]. Objectives to describe the frequency of clinically significant interstitial lung disease (ILD), determining the reduction of the forced vital capacity (FVC) or the alveolar-capillary diffusion of carbon monoxide (DLCO) in a group of 25 patients with SSc-RA compared to a control group of 570 patients with SSc alone. Methods data were retrieved from a database and from medical records of patients followed at the outpatient clinic dedicated to SSc of the Rheumatology Unit of S. Anna Hospital, Ferrara. All patients fulfilled the classification criteria for SSc (ACR 1980 and LeRoy 2001) and RA (1987). For both groups (SSc and SSc-RA) the following seroimmunologic data were assessed: anticentromere antibodies (ACA), anti topoisomerase 1 (Scl 70), rheumatoid factor (RF) and anti-citrulline (ACPA). Pulmonary involvement was assessed by high-resolution chest CT scan using the score of Warrick, and spirometry including DLCO. A cut-off of Warricks score able to detect patients with ILD has been identified by the application of a regression curve between the total score at HRCT and spirometry data (FVC and/or DLCO <75% as predicted); the analysis identified a value>10 able to alter lung function. Results in the SSc control group FR was available in 38% of cases and ACPA only in 8.9% RF and ACPA were available in all 25 SSc-RA patients. Positivity for both FR and ACCP was detected in 23 SSc-RA patients whilst 2 were seronegative. ILD was more frequent in SSc-RA group compared to SSc (76% VS 33%, p<0.05, OR 6.43). The SSc-RA/ACA + group presented a higher frequency of ILD than in SSc/ACA + (54.5% VS 21.7%, p<0.05, OR 4:33) as if the known protective role of the ACA for the development of ILD was less relevant in SSc-RA. In the SSc group, the positivity of the RF seems to be associated with the risk of developing ILD only in patients ACA/Scl 70 negative (72% vs. 28%, p<0.05, OR 6.3). Due to missing data it was not possible to perform the analysis for the ACPA in SSc group. Conclusions an increased risk of ILD in SSc-RA compared to SSc was confirmed. In SSc-RA group, ACA seems to lose its role as a “protective” factor against the possible development of pulmonary fibrosis. If this information is confirmed, in SSc-RA patients, despite their ACA positivity, it could justify a more “tight” clinical-instrumental follow-up, to detect lung involvement early and to monitor its evolution. References Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity. Szücs G, Szekanecz Z, Zilahi E et al. Rheumatology (Oxford). 2007 Jun;46(6):989-93 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5137

Semeiology of “early arthritis”

The main problems related to early arthritis are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the early arthritis clinics (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks - 6 months), morning stiffness of at least 1 hour, arthritis in >/= 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration.