BackgroundThe majority of patients with axial spondyloarthritis (SpA) response to anti-TNF therapy. However, discontinuation of this therapy due to different reasons is still a relevant problem. Currently, there is not enough data to know exactly which is the prevalence and causes of interruption of anti-TNF therapies in clinical practice.ObjectivesFirst, to evaluate the frequency and causes of discontinuating adalimumab or infliximab as the first anti-TNF in patients with axial SpA in clinical practice. Second, to investigate the influence of anti-drug antibodies (ADA) on these causes.MethodsA total of 326 patients with axial SpA who had received adalimumab (34%) or infliximab (66%) as a first anti-TNF therapy were included in this retrospective, observational study performed in a tertiary hospital. Disease activity (BASDAI, ASDAS, CRP and ESR) was measured before starting anti-TNF therapy, after 6 months and when interrupting the therapy to assess properly whether the reason for discontinuation was primary or secondary failure. Serum drug levels and/or ADA were measured at 6 months visit and at the end of anti-TNF treatment.ResultsA total of 99 (30.4%) patients discontinued treatment. Mean (SD) under anti-TNF therapy until discontinuation was 2.5 (2.9) years. Characteristics of these patients when initiating anti-TNF therapy are shown in Table 1. The reason to interrupt treatment was: primary failure in 22.2%, secondary failure in 36.4%, side effects 32.3%), and other reasons in 9.1%. Serum drug levels and ADA were available in 83 patients. In most patients with ADA positive (14/17), the reason for discontinuation was secondary failure. Out of those patients who discontinued due to secondary failure, 38.9% had ADA positive.ConclusionsIn our cohort of patients with axial SpA treated with adalimumab/infliximab, 30% of patients discontinued anti-TNF therapy. The main reason to discontinue treatment was secondary failure, which was related to the presence of ADA in almost 40% of patients.Disclosure of InterestE. Moral Grant/research support from: Funded by an unrestricted medical grant from Pfizer, C. Plasencia: None declared, V. Navarro-Compán: None declared, D. Pascual Salcedo: None declared, T. Jurado: None declared, C. Tornero: None declared, A. Pierens: None declared, M. B. Paredes: None declared, P. Bogas: None declared, I. Monjo: None declared, E. Martin Mola: None declared, A. Balsa: None declared

BackgroundBiologic therapy has been a major change in Rheumatoid Arthritis (RA) prognosis, but around 40% of patients (pts) fail to respond. Part of this treatment failure can be explained by the development of anti-drug antibodies (ADA), but the ADA-associated secondary inefficacies rate is currently unclearObjectivesTo assess in our AR cohort treated with Adalimumab (Ada), Infliximab (Ifx), etanercept (Etn), certolizumab (Czp), Tocilizumab (Tcz) and Abatacept (Abt) as 1st biologic agent, the frequency of drug suspension as well as the main causes for discontinuation and the secondary inefficacy rate associated with the development of immunogenicityMethodsFrom the RA cohort that initiated their 1st biologic agent at Hospital La Paz between 2005 and 2016, only those who had suspended those drugs were included, and causes for suspension were collected. Clinical activity was measured by DAS28 and Delta-DAS28 at 6 months of treatment to classify discontinuation by primary or secondary inefficacy. Drug levels (DL) and/or ADA were also measured by ELISA at 6 months since initiating the biologic agent in 43 pts and at drug discontinuation in 59 pts. Primary inefficacy was defined as DAS28>3.2 and delta-DAS28 <1.2 at 6 months with DL present. Secondary inefficacy was defined both as DAS28>3.2 plus delta-DAS28 <1.2 at 6 months with ADA+ and Delta-DAS28>1.2 or DAS28 <3.2 at 6 months with subsequent loss of efficacy. Statistical analysis was performed using SPSS version 20.0ResultsFrom the 246 pts who started their first biologic therapy, 144 (58%) pts who had definitively discontinued were included. [Ifx (n 35, 24%), Ada (n 40, 28%), Etn (n 30, 21%), Czp (n 23, 16%), Tcz (n 10, 7%) y Abt (n 6, 4%)]. 116 (80,6%) were women. The mean age was 56.3±14.7 years. The mean time of biologic was 2.23±1.96 years. From the global cohort, 18 (12.5%) drop out the treatment due to primary inefficacy, 41 (28.5%) to secondary inefficacy, 57 (39.6%) to adverse effects (AE), 11 (7.6%) to remission and 17 (11.8%) to other causes (surgery, pregnancy, etc.). 12.5% pts who discontinued due to AE or other causes had also a primary or secondary inefficacy; by including those pts in these last causes for suspension, a total of 20 pts (14%) failed due to primary inefficacy and 57 pts (39.6%) to secondary inefficacy. The most frequent AEs were: infections (35%), cutaneous AEs (psoriasis, rash, etc. (10.5%), infusion reactions (9%) and neoplasia (9%). Of the 59 pts who had DL/ADA measured at drug discontinuation, 42.4% were ADA +. Within the group that failed due to secondary inefficacy and had DL/ADA determined, 50% were ADA+; nevertheless this rate was smaller in suspensions due to other causes. Likewise, in the ADA+ pts, 73% suspended due to secondary inefficacyConclusionsIn our RA cohort, adverse effects were the main cause for discontinuation, with infections at 1st place. The 2nd cause conditioning interruption was the secondary inefficacy, in which 50% of our pts were ADA+ at drug discontinuation. These data suggest that the development of ADA ...

BackgroundBiological agents against tumor necrosis factor (Anti-TNF) have revolutionized the treatment of Rheumatoid Arthritis (RA). Recent studies assess the possibility of reducing the dose or increase the interval of administration of biologics (optimization strategy: OS) in patients with at least sustained low disease activity (LDA) without relevant clinical worsening. One of the questions raised is whether the use of OS could increase the incidence of anti-drug antibodies (ADA) appearance with the consequent loss of efficacy.ObjectivesTo evaluate the influence of the OS in a cohort of RA patients at least in LDA on the clinical activity (DAS28), incidence of flares, serum drug levels and ADA appearance.MethodsA retrospective observational study of a cohort of RA patients in LDA or remission (measured by DAS28<3.2 or<2.6, respectively) for at least 6 months. Of the 283 RA patients treated in our Unit with Infliximab (Ifx), Adalimumab (Ada) and Etanercept (Etn), 54 patients treated with the 1st Anti-TNF fulfilled the previous criteria to be included and were under an OS. DAS28, C reactive protein (CRP) values and drug and ADA levels were evaluated at baseline before OS (pre-visit) and in the last available visit during the first 2 years of follow-up (pos-visit). Flares were monitored between pre and pos-visits.ResultsOf the 54 patients, 77.8% were women. Mean age was 60.2±12 years. The 79.6% (43) were antiCCP and FR positive. Regarding concomitant treatment 35 patients (64.8%) received methotrexate at baseline, 25 (46.3%) other DMARDs and 23 (42.6%) prednisone. Twenty-seven (50%) were treated with Ada, 16 (29.6%) with Etn and 11 (20.4%) with Ifx. No significant differences were observed in the control of DAS28 between the pre-visit and pos-visit in every Anti-TNF (Ada: 2,13±0,12 pre-visit vs 2,42±0,18 pos-visit, p=0,064; Ifx: 2,32±0,11 pre-visit vs 2,19±0,18 pos-visit, p=0,799; Etn: 2,36±0,12 pre-visit vs 2,93±0,20 pos-visit, p=0,056). There was no statistically a significant increase in CRP levels between pre and post visits in any Anti-TNF (Ada: p=0,629; Ifx: p=0,799; Etn: p=0,796). Nineteen (35.2%) developed flares during the follow-up (14 patients had one flare and 5 had 2 flares). All patients were negative for ADA at the pre-visit, 5 (9.25%) were positive at pos-visit associated with flares. Sixteen (29.6%) out of the 19 patients with flare required to shorten the interval or increase the dose to control DAS28. A statistically significant decrease was observed in drug levels between the pre-visit and post-visit in patients treated with Ada and Etn (Ada: 5127.88±1542.65 pre-visit vs 1200.29±276.52 pos-visit, p=0.003; Etn: 2794.46±367.07 pre-visit vs 1359.38±375.121 pos-visit, p=0.023).ConclusionsOS seems to be feasible in RA patients in LDA treated with Anti-TNF, reducing the amount of drug administered with low incidence of ADA and without impact on clinical and serological markers such as CRP. In most patients with flares, the clinical activity appears to be controlled by shortening the interval of admin...

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Stroke can be one of the most severe complications of Infective Endocarditis (IE) and it happens in 14% of patients with IE. Therefore, we aimed to review stroke frequency in patients diagnosed with IE in our hospital from 2010 to 2020. We defined it as IE-Associated Stroke (IEAS) when the stroke happened one month before or after IE's diagnosis. Sixty-six patients were diagnosed with IE during this period time and 15 (22%) suffered IEAS: 13 ischemic strokes, one Subarachnoid Hemorrhage (SAH) and one parenchymal hemorrhage with SAH. Patients with IEAS were more frequently men (80% vs 51% p = 0.042) and had less atrial fibrillation (13.3% vs 37.3%, p = 0.071).Although not statistically significant, Streptococcus sp (53% vs. 44.9%) and Staphylococcus aureus (33.3% vs. 16.3%) were more frequent in patients with IEAS. Mortality was increased in patients with IEAS (60% vs 13.7%, p = 0.001) especially in patients where stroke diagnosis was posterior to IE (88.9% vs 16.7%, p = 0.011). Hypertension (93.8% vs 63%, p = 0.013) and diabetes (53.2% vs 30%, p0 = 0.052) were also more frequent in those patients who died. In multivariate analysis, hypertension (OR 13.7 95% CI 1.4-138.4) and IEAS (OR 12.8 95% CI 2.8-58) were independently associated with death. The frequency of IEAS in our patients is comparable to what has been described in the literature. IEAS was associated with increased mortality.