L. Lojo

The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a second anti-TNF therapy in spondyloarthritis patients

IntroductionAnti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients.MethodsForty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration.ResultsAll patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).ConclusionsIn SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.

El uso de abatacept en artritis reumatoide: revisión de la evidencia y recomendaciones

OBJECTIVE To review the clinical evidence on abatacept and to formulate recommendations in order to clear up points related to its use in rheumatology. METHOD An expert panel of rheumatologists objectively summarized the evidence on the mechanism of action, practicalities, effectiveness and safety of abatacept, and formulated recommendations following a literature review. The level of evidence and degree of recommendation was established. RESULTS The document presents 21 statements focused on evidence or recommendations on abatacept (14 evidence summaries and 9 recommendations). The level of evidence was 2b or higher according to the Oxford Centre for Evidence-Based Medicine scale on 14 occasions. The degree of the recommendation was A in two recommendations, C in one, and D in the rest. It was considered important to make recommendations on aspects with lower levels of evidence. CONCLUSIONS This is a practical document to supplement the summary of product characteristics.

AB0573 The immunogenicity of biological therapies correlates with clinical efficacy in psoriatic arthritis (psa) in long-term treatment with infliximab and adalimumab.

Background In psoriatic arthritis (PsA) with peripheral involvement classical DMARDs refractory, the anti-TNF therapy has proven to be effective. In recent years, there are some publications that demostrate the correlation between clinical activity and the anti-drug antibodies (ADA) development in rheumatic diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). To date, there is no studies that reveals theses findings in PsA patients treated with infliximab (Ifx) and adalimumab (Ada). Objectives To evaluate in PsA patients treated with Ifx and Ada wether the development of ADA correlate with clinical activity and biological treatment discontinuation. Methods We studied 37 patients with PsA treated with Ifx and Ada from La Paz University Hospital. Clinical activity was assessed using the Disease Activity Score 28 (DAS28), clinical improvement by the delta-DAS28 and treatment response by EULAR criteria at baseline, at 6 months, at 1 year and at > 2nd years of treatment. Ifx and Ada were administred at standard therapeutic schedule. Serum drug and ADA levels were measured by ELISA. Statistical analysis was performed using SPSS 11.0. Results Of the total of patients, 24/37 (64.9%) were treated with Ifx and 13/37 (35.1%) with Ada, being female 23 (62.1%). The mean age was 55.1 ± 12.3 years and the mean disease duration was 14.4 ± 9.9 years. The average time on biological therapy was 4.4 ± 3.2 years. Most patients received concomitantly classical DMARDs [29/37 (78.3%) with DMARDs vs 8/37 (21.7%) in monotherapy]. At baseline, clinical activity (DAS28) was higher in patients who subsequently not developed ADA (5.1 ± 0.9 without ADA vs 13.4 ± 0.6 with ADA, p = 0.021). Clinical activity (DAS28) tended to be higher in patients with ADA at all studied time points (5.4 ± 1.2 with ADA vs 2.8 ± 1.3 without ADA at 6 months, p = 0.007; 4.0 ± 1.2 with ADA vs 3.0 ± 1.3 without ADA at 1 year, p = 0.144; 2.9 ± 1.3 with ADA vs 2.4 ± 0.4 without ADA a> 2nd year, p = 0.169). Clinical improvement (delta-DAS28) was lower in patients with ADA throughout the study (-1.0 ± 1.6 with ADA vs 2.0 ± 1.4 without ADA at 6 months, p = 0.006, 0.3 ± 1.8 with ADA vs 2.1 ± 1.5 without ADA at 1 year, p = 0.052; 0.9 ± 1.5 with ADA vs 2.7 ± 0.8 without ADA a> 2nd year, p = 0.007). Patients without ADA were classified as responders more frequently based on criteria EULAR [2/5 (40%) with ADA vs. 27/30 (90%) without ADA, p = 0.006]. The median time to drug discontinuation was lower in patients with ADA (4.83 ± 1.6 years with ADA vs 7.93 ± 1.4 years without ADA, p = 0.061). The dose increase was more frequent in patients with ADA [3/6 (50%) with ADA vs 4/31 (12.9%) without ADA, p = 0.053], and in contrast, in patients without ADA was more often performed dose decrease of anti-TNF therapy [0/6 (0%) with ADA vs 15/31 (48.3%) without ADA, p = 0.053]. Conclusions The development of ADA correlates with poorer clinical response and more frequent treatment discontinuation in PsA patients in long-term treatment with Ifx and Ada. Disclosure of Interest None Declared

Teaching enthesis ultrasound: experience of an ultrasound training workshop

To evaluate a standardised enthesis ultrasound training method, a workshop was conducted to train rheumatologists on enthesis ultrasound. After a theoretical session about ultrasound elementary enthesis lesions (changes in tendon architecture/thickness, bone proliferation/erosion, bursitis or Doppler signal), a reading exercise of 28 entheses’ ultrasonographic images (plantar fasciae, Achilles, origin and insertion of patellar tendon) was completed. Participants scored through an electronic multiple-choice device with six possible lesions in each enthesis. To assess the adequacy and efficacy of the workshop, we explored the following: (1) subjective outcomes: a 12-item structured satisfaction questionnaire (graded 1–5 using Likert scale) and (2) objective outcomes of reliability: sensitivity (Se), specificity (Sp) and percentage of correctly classified cases (CC). Forty-nine participants attended the workshop. The satisfaction questionnaire demonstrated a 4.7 mean global value. The inter-reader Kappa reliability coefficient was moderate for the plantar fascia (0.47), Achilles tendon (0.47), and distal patellar tendons (0.50) and good for the proximal patellar tendon (0.63). The whole group means comparing to teachers’ consensus were as follows: (a) plantar fascia: Se, 73.2%; Sp, 87.7%; CC, 83.3%; (b) Achilles: Se, 66.9%; Sp, 85.0%; CC, 79.5%; (c) distal patellar tendon: Se, 74.6%; Sp, 85.3%; CC, 82.1%; and (d) proximal patellar tendon: Se, 82.2%; Sp, 90.6%; CC, 88%. The proposed learning method seemed to be simple, easily performed, effective and well accepted by the target audience.

Registro de pacientes con miopatía inflamatoria de la Sociedad Madrileña de Reumatología: análisis descriptivo

OBJECTIVE To analyze clinical characteristics, survival and causes of death of patients diagnosed with autoimmune inflammatory myositis in the REMICAM registry from the Society of Rheumatology in the Community of Madrid (SORCOM). METHODS Multicenter cohort of patients diagnosed with autoimmune inflammatory myopathy with follow-up between January 1980 and December 2014. A total of 313 variables concerning demographic, clinical and morbidity data were collected, and a comparison was performed between clinical subgroups. RESULTS A total of 479 patients were recruited from 12 centers, with 14% of patients lost to follow-up. Seventy-four percent of cases were women, age at diagnosis of 44±23 years and a mean follow-up period of 10±8 years. The most frequent clinical subgroups were primary myositis (PM 29%, DM 22%), followed by overlap myositis (20.5%), juvenile myositis (18%), myositis associated with cancer (8%), immune-mediated necrotizing myositis (1%) and inclusion body myositis (1%). During the follow-up period, a total of 114 deaths (28%) were registered, the main causes being cancer (24%), infections (23%) and cardiovascular events (21%). CONCLUSIONS A total of 479 patients were recruited in the REMICAM registry of inflammatory myopathies. Including sociodemographic, clinical and prognostic information, it represents the largest Spanish multicenter registry to date in rheumatology, and constitutes an important source for conducting further substudies.

THU0282 Clinical efficacy to a second anti-tnf therapy is associated with the development of antibodies against the first anti-TNF therapy in patients with spondyloartrhitis

Background Spondyloarthropathies (SpA) include a heterogeneous group of rheumatic diseases that mainly affect the axial skeleton and entheses. Despite the anti-TNF therapy has been demonstrated effective in SpA patients, about 30% of them develop primary or secondary inefficacy. In rheumatoid arthritis (RA) has been shown that the development of antibodies (Ab) against the first anti-TNF determines the clinical response to a second anti-TNF. Objectives To assess if the effectiveness of second anti-TNF therapy is associated with the development of Ab against the first anti-TNF in SpA patients switching to a second anti-TNF. Methods We studied 33 SpA patients treated with a second anti-TNF after having an inadequate response to the first anti-TNF therapy. The diagnoses were: 23 (69.7%) Ankylosing Spondylitis (AS), 6 (18.2%) undifferentiated SpA, 2 (6.1%) psoriatic SpA, 1 (3%) SpA associated with inflammatory bowel disease and 1 (3%) reactive SpA. Clinical activity was measured by ASDAS-CRP at baseline to the 1st and 2nd anti-TNF treatment and after 6 months of the switching. Clinical improvement was assessed by the Delta-ASDAS (clinically important improvement ≥1.1). Drug through levels and anti-drug Ab were measured by ELISA at the end of the fist anti-TNF treatment. Statistical analysis was performed using SPSS 11.0. Results Our cohort included 33 patients, 18 (54.5%) male, mean age of 50.09±10 years and 21 (63.6%) HLA B27 positive. All of them were initially treated with an anti-TNF: 14 (42.4%) with infliximab (Ifx), 3 (9.1%) with adalimumab (Ada), 16 (48.5%) with etanercept (Eta). Nine out of 33 (27.3%) developed anti-drug Ab [8 anti-Ifx Ab (ATI) and 1 anti-Ada Ab (AAA)]. All patients switched to a 2nd anti-TNF, due to inefficacy: 7 (21.2%) to Ifx, 16 (48.5%) to Ada, 5 (15.2%) to Eta, 5 (15.2%) to golimumab. Clinical activity (ASDAS-CRP) was not different at baseline between first and second anti-TNF therapy (3.45±0.99 vs 3.22±0.96, p=0.24). No differences were observed between patients who developed or not anti-drug Ab at baseline to the first (3.34±0.87 with Ab vs 3.50±1.04 without Ab, p=0.93) and second (2.99±0.95 with Ab vs 3.31±0.96 without Ab, p=0.37) anti-TNF treatment. After 6 months of switching to a second anti-TNF, patients who had developed anti-drug Ab had lower clinical activity (ASDAS-CRP) than patients without anti-drug Ab (1.76±0.98 with Ab vs 2.79±1.10 without Ab, p=0.021). Moreover clinical improvement was higher in patients with anti-drug Ab (1.23±1.22 with Ab vs 0.52±1.08 without Ab, p=0.063). Most patients who had clinically important improvement had anti-drug Ab before switching [60% (6/10) vs 40% (4/10), p=0.010]. Conclusions Same as in RA, in SpA, the failure to a first anti-TNF therapy associated with the development of anti-drug Ab predicts a better clinical response to a second anti-TNF. The study of the immunogenicity in the biological treatment failure helps predict the response to a second biological treatment in SpA. Disclosure of Interest None Declared

FRI0301 Prognosis of The Idiopathic Inflammatory Myopathies Associated with Interstitial Lung Disease: Preliminary Analysis of The Registry Remicam

Background Some studies suggest that clinical subgroups of idiopathic inflammatory myopathies (IIM) and several myositis-specific antibodies (MSAs) could influence the prognosis of IIM with interstitial lung disease (ILD). Objectives To investigate the prognosis value of different clinical subgroups and of MSAs in a cohort of patients with IIM -associated ILD. Methods We analyzed patients with IIM-associated ILD included in the multicenter registry REMICAM (1980–2014). We compared prognosis between a) subgroups of IIM: dermatomyositis (DM) vs. polymiosytis (PM) (primary, juvenile, cancer-associated myositis or overlap myositis); and b) absence (−) or presence (+) of anti-Jo1 vs. anti-RO vs. anti-Jo1 and anti-RO. In this preliminary analysis, outcomes were mortality and change between final and initial visit in FVC and DLCO. Results 478 patients were included in the registry, of which 143 had ILD, 66% PM and 34% DM. The distribution by MSAs was: 56% anti-Jo1-/RO-, 20% anti-Jo1+, 9% anti-RO+ and 15% anti-Jo1+/RO+. There were 52 deaths; the main causes were 32.6% cardiovascular events and 22.4% infections without difference between subgroups of IIM. The probability of survival was 50% to 18.8 years and the mortality rate was 37.7/1000 patient-ys. We did not find differences when we compared survival between subgroups of IIM or we compared by MSAs. FVC seemed to improve more in DM than in PM patients (1.2±5.2vs. 0.5±4.7;p=0.059), but there were no significant changes in DLCO of DM patients or in FVC and DLCO according to MSAs. Conclusions We did not find prognostic differences in the causes of mortality, mortality rate between subgroups of IIM, or in mortality rate according to MSAs in patients with ILD. In DM patients there was a trend towards a greater improvement of FVC than in PM patients. Disclosure of Interest None declared

AB0612 Multicenter Registry on Inflammatory Myopathies in Madrid (REMICAM): Descriptive Analysis

Background Clinical manifestations, evolution and prognosis of idiopathic inflammatory myopathies (IIM) are very heterogeneous which, together with its low prevalence, limits the study of the disease. Objectives To analyze the clinical characteristics of patients diagnosed of IIM in a multicenter study. Methods A multicenter retrospective descriptive study from REMICAM1 myositis study group was performed. All patients were diagnosed with IIM according to Bohan and Peter2 criteria, were followed up sometime between January 1980 and December 2014 and were classified into 7 different clinical subgroups: primary dermatomyositis (DM), primary polymyositis (PM), juvenile dermatomyositis (JuvM), cancer associated myositis (CAM), overlap myositis (OM), inclusion body myositis (IBM) and necrotizing myositis (NM). Results 478 IIM cases were included. 74% of the cases was women, with an age at diagnosis of 43.7±22.6 years, and an average follow-up time of 9.7±8.3 years. The main IIM subgroups were primary myopathies (PM 28%, DM 22%, OM 19.9%, JuvM 19.2%, CAM 8.4%, NM 1.3%, BMI 1.3%). The connective tissue diseases more frequently associated in OM subgroup were MCTD (30%), systemic sclerosis (27%) and SLE (18,9%). The main extramuscular manifestations were cutaneous lesions (65%), arthritis (43%), general symptoms (39%) gastrointestinal complications (33%), and interstitial lung disease (ILD) (30%). Patients with OM had a higher prevalence of ILD (46.8% vs. 25.8%;p<0.001), Raynaud (67% vs. 19.4%;p<0.001), arthritis (70% vs. 35.8%;p<0.001) and cytopenias (55.9% vs. 21.5%; p<0.001), whereas JuvM patients developed more calcinosis (30.4% vs. 5.7%;p<0.001) but fewer serious infections (4.7% vs. 29.3%;p<0.001). During the period of study 114 patients died (24%), and the main causes of death were infections (24%), cancer (24%) and cardiovascular events (22%). Conclusions In this multicenter REMICAM registry 478 IIM cases have been included. The most common subtypes were primary myopathies, and the most frequent extramuscular manifestation were typical cutaneous lesions. Overlap myositis patients presented with more extramuscular manifestations than the other subgroups. References REMICAM: Registry on inflammatory myopathies from Madrid Bohan A, Peter JB. N Engl J Med 1975 Feb 13;292(7):344–7. Disclosure of Interest None declared

FRI0289 Multicenter Registry on Inflammatory Myopathies in Madrid (REMICAM): Mortality Analysis

Background Classically the prognosis of idiopathic inflammatory myopathies (IIM) has improved in recent decades, but can still be poor in certain subgroups or in the presence of some clinical factors. Objectives To analyze survival, causes of death and poor prognosis factors in a cohort of patients diagnosed with IIM. Methods A multicenter retrospective study from REMICAM1 myositis study group was performed. All patients were diagnosed with IIM according to Bohan and Peter2 criteria and were classified into 5 different clinical subgroups: primary dermatomyositis (DM), primary polymyositis (PM), juvenile dermatomyositis (JuvM), cancer associated myositis (CAM) and overlap myositis (OM). Results 478 IIM cases were included. 74% of the cases were women, with an age at diagnosis of 43.7±22.6 ys. and a mean follow-up of 9.7±8.3 ys. During the follow-up period there were a total of 114 deaths (24%), the main causes were infections (24%), cancer (24%), and cardiovascular events (22%). Factors associated with poor prognosis were CAM (HR 15.4) and OM subgroups (HR 4.55), older age at diagnosis (HR 1.05), shorter time of disease (HR 1.30), serious infections (HR 4.57), cancer (HR 3.07), systemic symptoms (HR 1.64), heart (HR 2.52) and haematological manifestations (HR 1.53), ESR/CRP elevation at baseline (HR 3.05) and chronic renal failure (HR 2.41). The clinical characteristics that showed a protective effect were arthralgia (HR 0.68), typical skin lesions (HR 0.62), drug use (HR 0.53) and female sex (HR 0.5). In multivariate analysis the independent variables associated with mortality were CAM (HR 8.83) and OM (HR 5.17) subgroups, severe infections (HR 3.42), older age at diagnosis (HR 1.03), shorter course of the disease (HR 1.34), thrombocytopenia (HR 2.93) and elevated ESR/CRP (HR 2.47). Conclusions In our REMICAM registry on inflammatory myopathies 24% of patients died, mainly due to infections, cancer and cardiovascular events. The independent predictors of mortality were belonging to the subgroups of paraneoplastic myopathies or overlap syndrome, the presence of severe infections, thrombocytopenia, elevated ESR/CRP at baseline, shorter course of the disease and older age at onset. References REMICAM: Registry on inflammatory myopathies in Madrid Bohan A, Peter JB. N Engl J Med 1975 Feb 13;292(7):344–7. Disclosure of Interest L. Nuño Grant/research support from: SORCOM-MSD grant for myositis study, M. J. García: None declared, B. Joven: None declared, V. Maldonado: None declared, I. Llorente: None declared, C. Barbadillo: None declared, P. García de la Peña: None declared, L. Ruiz: None declared, H. Moruno: None declared, T. Cobo: None declared, R. Almodovar: None declared, L. Lojo: None declared, F. J. Lόpez Longo: None declared

SAT0462 Mortality and Main Causes of Death in a Multicenter Cohort of Inflammatory Idiopathic Myositis

Background Clinical manifestations and prognosis of idiopathic inflammatory myopathies (IIM) are extremely heterogeneous which, combined with its low prevalence, makes difficult the study of the disease in the absence of multicenter studies. Objectives To analyze the clinical characteristics and mortality in a cohort of patients diagnosed with IIM in rheumatology units from several hospitals in Madrid. Methods A multicenter retrospective longitudinal descriptive study from REMICAM myositis study group was performed. All patients diagnosed with IIM according to Bohan and Peter1 criteria for myositis and in follow-up sometime between January 1980 and December 2014 in rheumatology units were included. Patients were classified into clinical subgroups: primary dermatomyositis (DM), primary polymyositis (PM), juvenile dermatomyositis (JDM), paraneoplasic myositis, overlap myositis (OM), inclusion body myositis (IBM) and necrotizing myositis (NM). Main causes of death and influence of age and sex were studied. Results 485 cases were included in this study, with a medium age at diagnosis of 43,3±23,2 years and mean follow-up time of 11,3±19 years. Most cases were Caucasian (93%), and women (74,4%). The most frequent form of classification were primary myopathies (28,8% PM; 21% DM; 20,6% OM; 19,4% JDM; 8,3% paraneoplasic myositis; 1% IBM and 0.8% NM) and the most frequent myositis specific antibodies detected were anti-Jo-1 (16,3% anti-Jo-1; 4,1% anti-Mi-2; 2,7% anti-PM-Scl; 0,6% anti-SRP; 0,2% anti-Ku). 25,4% of patients died, with a higher mortality rate in men (32,5% vs. 22,9; p=0,04) and older age at onset (54,1±24,8 years vs. 37,2±26,4 years, p<0,001). The clinical subtypes with higher mortality were paraneoplasic myositis (70%) and OM (36%). Main causes of death were cancer (23,4%) and cardiovascular events (23,4%), followed by infections (22,4%), interstitial lung disease (7.5%) and other causes. In clinical subsets, main causes of death were infections in DM (37,5%), and cardiovascular disease in OM (32,3%) and PM (32,1%). Conclusions In our cohort of IIM 25,4% of patients died, with a worse prognosis in men and older age at onset, mainly due to cancer and cardiovascular events. Cardiovascular events are the most important cause of death in PM and MCTD, and infections in DM. References Bohan A, Peter JB. N Engl J Med 1975 Feb 13;292(7):344-7. Disclosure of Interest None declared