PO.7.156 Table 1 Reason of disagreement between patients that did not fulfill LLDAS definition and expert assessment as remission or low disease activity SLEDAI: systemic lupus erythematosus; CNS: central nervous system; PGA: physician global assessment Abstracts A114

Background:Osteoarthritis (OA) incidence has skyrocketed in the last decade and yet a definitive treatment has still to be found. This worldwide disease is depriving our society from their life quality and has become a grave economic burden. Research on anti-inflammatory tools has been done on traditional Asian medicine. Boswellic acid is a plant-derived molecule from the Boswellia species that has shown to prevent cartilage loss in an OA mouse model[1]. However, the specific mechanism of action is still unclear. The activation of innate immune receptors, such Toll-like receptor 4 (TLR4) has been involved in chondrocyte-mediated inflammatory responses and OA development. Although, boswellic acid has shown an inhibitory effect on TLR4-mediated inflammatory responses little is known about its role on TLR4-mediated chondrocyte inflammatory and catabolic responses.Objectives:Determine the ability of beta boswellic acid (BBA) to block TLR4-mediated innate immune responses in chondrocytes and synoviocytes.Methods:In silicoThe binding affinity of beta boswellic acid (BBA) to TLR4 complex signalling was determined by optimized docking algorithm in the BIO-HPC Research Group facilities.In vitroCellular proteome and secretome profiling (LC-MALDI/TOFF) was used to study inflammatory pathways induced by the agonist of TLR4 (LPS [100ng/ml]) and IL1R (IL1β [0.1ng/ml]). The effect of BBA on TLR4-mediated innate immune responses was determined by RT-PCR, Western Blot and ELISA in primary human OA chondrocytes (hOC), murine ATDC5 chondrocytes, human synoviocytes (SW982) and primary human osteoblasts (hOB). Cell viability was tested using the methyl-thiazolyl-tetrazolium (MTT) reagent. Nitric oxide production in cell culture media was assessed by Griess reaction. Green Malachite Assay was used to semi-quantify the whole phosphoproteome.EthicsThis study was approved by the CEIC (CAEIG 2014/310).Results:Cellular proteome and secretome profiling validated the activation of TLR4 and IL1R signalling by LPS and IL1β ligands and revealed an enrichment in innate immune responses (NF-Kβ, NLRP3, MMPs, Interleukins, etc).Non-toxic doses of BBA [0.5-1000nM] prevented the activation of TLR4 in multiple articular joint cells and inhibited TLR4 & IL1R-dependant innate immune responses at the mRNA and protein level such as inflammatory factors IL6, NOS2, COX2, LCN2, MMP1, -3, -9, -13 and ADAMTS4, among others. Furthermore, NF-Kβ/IKBα and NLRP3/PYCARD/IL1β axis were also severely inhibited after BBA treatment. Moreover, these results were validated by in silico docking analysis that showed BBA interacted with TLR4/NF-Kβ.Conclusion:We prove that BBA inhibit TLR4 & IL1R -dependent innate immune responses in multiple human joint cells (Figure 1). We show that NF-Kβ & NLRP3 signalling, both associated to OA, are blocked (mRNA and protein) after BBA treatment (Figure 1).Our data support previous studies showing the prevention of cartilage loss in an OA animal models by BBA might come from its ability to inhibit TLR4 signalling. In the clinical practice of rheumatologists, Boswellia Serrata could be a useful nutraceutical to manage OA inflammation due to its content in BBA.Figure 1.References:[1]Wang, Q.; Pan, X.; Wong, H.H.; Wagner, C.A.; Lahey, L.J.; Robinson, W.H.; Sokolove, J. Oral and topical boswellic acid attenuates mouse osteoarthritis. Osteoarthr. Cartil.2014, 22, 128–132, doi:10.1016/j.joca.2013.10.012.Acknowledgements:Eloi Franco-Trepat and Ana Lois-Iglesias contributed equally to this work.This research has been funded by the non-profit FER (Fundación Española de Reumatologia /Spanish Foundation of Rheumatology) through the project “Búsqueda de nuevos fármacos bloqueantes de la inflamación asociada a TLR4 en condrocitos humanos artrósicos”.Disclosure of Interests:None declared

Background:Musculoskeletal disorders cause in Spain 23% of temporary work disability (TD). They are the first cause of permanent work disability (PD). A study of early intervention by a rheumatologist reduced TD days reduced PD. Using the “Fit for Work” European coalition led by AbbVie, the program was implemented nationwide.Objectives:To analyze the variation in the duration of sick leaves in patients referred to an early intervention program in relation to the delay on the referral from primary care and from the Occupational Health service of our hospital.Methods:Cross-sectional observational study of a hospital cohort of patients referred for 34 consecutive months to the Rheumatology Early Intervention program due to TDdue to musculoskeletal pathologies. Patients whoseTD had a traumatic or surgical origin, or with incomplete information were excluded from the analysis. We created 4 groups of patients according to the time elapsed from the start of the TD until the referral to our office: 0 to 15 days, 15 to 30 days, 30-60 days or> 90 days. We compared the patients referred from primary care with those referred from occupational health.Results:For the analysis we included 394 patients, 63.3% women, with a mean age (±D.E.) of 48.5 (±9.8) years. We analyzed the most frequent pathologies: back pain (33.5%), shoulder pain (19.8%) and neck pain (8.4%). 85.8% came from primary care, 10.2% from occupational health and 4.1% from other units. The median time between referral and 1st consultation was 6 days. We found statistically significant differences in the total duration of TD among the patients referred to consultation in the first 30 days compared to those sent later in the 3 pathologies (decreasing the duration of TD between 50 and 100 days in low back pain, between 44 and 54 days in shoulder pain and between 13 and 20 days in neck pain). In back pain we found statistically significant differences in the duration of the TD after the 1st consultation, obtaining an average decrease in the duration of the TD between 42 and 52 days. In shoulder pain and neck pain an important decrease is observed without reaching statistical significance, probably related to the sample size.Regarding the patients referred from occupational health, the median time between TD and referral was 2.5 days. The pathology most frequently evaluated was low back pain (60% of cases), finding statistically significant differences in the total duration of TD, with a mean decrease in the duration of TD of 59 days compared to the general population.Abstract THU0496 – Figure 1Conclusion:Early intervention by rheumatologists in patients with TD due to musculoskeletal disorders reduces the duration of the processes, saving costs to the health system.Disclosure of Interests:None declared

ObjectivesTo study the prevalence of mycobacterial infection (MI), the associated factors and their clinical significance in patients included in a large SLE cohort.MethodsRetrospective descriptive study of RELESSER patients with a history of MI and analysis of the factors associated with this infection.ResultsIn RELESSER 3,658 patients with ≥4 ACR SLE criteria were included. 90% are women with a mean age of 32.9 years. 93% are Caucasians. The mean follow-up time (± SD) was 120.2 (± 87.6) months. 705 (19.3%) patients had ≥1 severe infection (defined as requiring admission); 1,227 severe infections occurred. MI were diagnosed in 42 patients (1.2% of all RELESSER patients, 3.4% of all severe infections), 85.7% women. The incidence rate of MI was 1 per 1,000 patients/year (95% CI:0.7–1.4).MI presentation was pulmonary in 18 (42.9%) patients and extrapulmonary in 24 (57.1%) patients [joints in 8 (19.0%) patients, soft tissue in 6 (14.3%) and other sites in 10 (23.8%)]. The extrapulmonary form was associated with immunosuppressants use: 84.6% of the 13 patients treated with immunosuppressive drugs versus 44.4% of the 27 patients without (p=0.01). We did not observe this association with the use of corticosteroids.To study the factors associated with MI, we performed a bivariate analysis including the variables associated with severe infection in RELESSER (age, sex, ethnicity, corticosteroids, immunosuppressants, antimalarials, previous admission by SLE activity, rituximab and anti-TNF use, Katz severity index, SDI index, SLEDAI index and Charlson comorbidity index). There is a statistically significant association with previous admission by SLE activity (RR:2.9, 95–95%:1.3–6.2, p=0.007), renal impairment (RR:2.0, CI 95%:1,1–3,7, p=0,04), the Katz score (RR:2.1, 95% CI:1.1- 4.0, p=0.04) and the Charlson index (RR: 2.5; 95% CI: 1.3–4.8, p=0.009). Damage (SDI>0) was closely associated with significance:RR: 2.0; 95% CI: 1.0–4.0, p=0.07. Iimmunosuppressants use was associated with an important increase in the risk of MI: RR:4.3; 95% CI:2.2–8.3, p=0.31.Two patients (4.8%) died (1 respiratory and 1 extrapulmonary). Mean survival after MI diagnosis in these cases was 21 days.ConclusionsMI in RELESSER affects 1.15% of patients. Its incidence rate is 1 per 1,000 patients/year (95% CI:0.7–1.4). Extrapulmonary localization affects more than half of the patients and is associated with immunosuppressants use. Previous admission by SLE activity, renal involvement, SLE severity and increased number of comorbidities are factors associated with MI.AcknowledgementsWork supported by Spanish Society of Rheumatology, FIS/ISCIII/FEDER (PI11/02857), BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012–2013.1(316265), GSK, Roche, Novartis, UCB.Disclosure of InterestNone declared

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