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Background Fluoroquinolones have been associated with increased risk of tendinopathy and Achilles tendon rupture (ATR), especially in patients over 60 years of age. Methods A retrospective study was carried out including patients over 60 years of age with ATR attended in our centre over the period 2000–2017. Results We identified 44 patients with RTA, of whom 18% (8/44) had been previously treated with fluoroquinolones, with a mean age at diagnosis of ATR of 77.37 years and concomitant corticotherapy in 4 of them. In 7 patients, the rupture was spontaneous and all required surgical management. A significantly higher frequency of smoking, concomitant corticotherapy and spontaneous ruptures were found in the group treated with fluoroquinolones. Conclusions ATR is an adverse event that can occur in patients over 60 years of age treated with fluoroquinolones, so an adequate risk-benefit assessment should be carried out in this population, especially in the presence of associated risk factors.

Background: Patients with Rheumatoid Arthritis (RA) have been traditionally treated with other TNF inhibitors (TNFis) after the withdrawal of a first TNFi (cycling). However, due to the increase in the biological therapy options, changing to a biologic agent with different mechanism of action (switching) is an alternative choice. More studies are needed to clarify the role of both strategies in order to guide treatment decisions. Objectives: To analyze the survival of the second biological drug, TNFi or biologic with a different mechanism of action, in patients with RA non-responders to the first TNFi. To evaluate factors associated with the survival of the second-line therapy. Methods: A retrospective, longitudinal, observational study was performed, which included patients diagnosed of RA and treated with biological therapies between 2008 and 2017, who discontinue a first-line TNFi and started a second-line biological therapy. The demographic and clinical data were obtained from their medical records. Kaplan Meier and Log-rank survival analysis were performed, as well as Cox regression to identify related factors. Results: 69 patients were identified, 14 men (20.3%) with a mean age at the beginning of the treatment of 52.68 ± 19.79 years. Demographic and clinical data are shown in the table. The main cause of withdrawal of the first TNFi was secondary failure (47.8%), followed by side effects (34.8%) and primary failure (13%). Cycling was performed in 34 patients (49.3%) and switching in 35 (50.7%). During the follow-up, the main causes of withdrawal of the second-line treatment were primary and secondary failure (10.1% in both cases). The survival analysis of the 42 patients who presented a primary or secondary failure to the first TNFi was stratified according to the cause of withdrawal of the second biological therapy. When cycling was chosen, the average treatment survival was 8.8 months (CI95%:4.8-12.8) whereas for the switching option it was 23 months (CI95%:5.4-40.5), being the differences statistically significant (p=0.049). Age was shown as a protective factor (HR=0.86, CI95%:0.76-98) and the positivity of Rheumatoid Factor (RF) as a risk factor (HR=4.76, CI95%:1.39-16.30) for the withdrawal of the second biological therapy. No differences were found in the withdrawal rate due to adverse effects among patients who performed switching or cycling (11.42% vs 5.88%, p=0.41). Conclusion: Switching strategy showed a greater drug survival time and was considered as a better option after the failure of a first TNFi. RF positivity was associated with an increased risk for the withdrawal of the second-line biological therapy. Reference: [1] Todoerti M, Favalli E, Iannone F, Olivieri I, Benucci M, Cauli A, Mathieu A, Santo L, Minisola G, Lapadula G, Bucci R, Gremese E, Caporali R. Switch or swap strategy in rheumatoid arthritis patients failing TNF inhibitors? Results of a modified Italian Expert Consensus. Rheumatology. 2018; 57: vii42–vii53 Disclosure of Interests: None declared

Background Fluoroquinolones (FQ) are a class of broad-spectrum antibiotics whose use has spread as they are considered safe and well tolerated drugs. Among its musculoskeletal side effects, Achilles tendon rupture (ATR) is a well-known complication that can be disabling, arising recent interest from the pharmacovigilance system after evaluating the reported side effects. Objectives To describe the epidemiological and clinical features of patients diagnosed with FQ-associated ATR in a Spanish tertiary hospital. Methods A retrospective observational study was performed, which included all patients older than 60 years who were diagnosed of ATR in our center during the period 2000-2017, identifying patients who had been previously treated with FQ. The demographic, clinical and outcome data were obtained from their medical records. Results During the study period, 44 patients with ATR were identified, 8 (14.6%) of them previously treated with FQ. In this group of patients, the mean age at diagnosis of ATR was 77.37 ± 9.54 years, being male 6 (75%). Four of them (50%) received concomitant treatment with corticosteroids (CS) and one patient had undergone kidney transplantation due to nephroangiosclerosis. Seven patients (87.5%) were treated with Levofloxacin and one case received Ciprofloxacin, all of them orally. The indication for FQ treatment in half of the cases was acute bronchitis and in the other half exacerbations of underlying respiratory pathology (chronic obstructive pulmonary disease and diffuse interstitial lung disease). The mean duration of treatment with FQ was 6.16 ± 2.4 days, while the mean time from the start of treatment to the diagnosis of ATR was 19.25 ± 14.83 days. In seven patients (87.5%) the rupture was spontaneous, while one patient presented traumatic rupture (low impact traumatism). 87.5% of the ruptures were total ruptures and all cases required surgical treatment, without recurrence reported. The comparison of the characteristics of patients with ATR who had or not received treatment with FQ is shown in the table, identifying significant differences in favor of a higher percentage of patients who were smokers, received concomitant treatment with CS and had spontaneous rupture in the group of patients who had received FQ. Conclusion The Achilles tendon is the most frequent location of tendinopathy associated with FQ, being affected in 95% of cases. The risk factors associated to an increased risk to develop FQ-associated ATR includes age over 60 years, male gender, chronic treatment with CS and organ transplantation, all these being present in our cases. Despite being a relatively frequent adverse event, it is underdiagnosed and the risk of ATR is not usually assessed when indicating FQ treatment. It is important to perform a risk/benefit assessment, specially in patients with associated risk factors, because most ruptures are complete and require surgical treatment, and may be a potential cause of disability. References [1] Bidell M, Lodise T. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk?. Pharmacotherapy. 2016;36(6):679-93. [2] Godoy-Santos A, Bruschini H, Cury J, Srougi M, De Cesar N, Fonseca L, Maffulli N. Fluoroquinolones and the Risk of Achilles Tendon Disorders: Update on a Neglected Complication. Urology. 2018;113:20-25. Disclosure of Interests None declared

Background: Systemic Juvenile Idiopathic Arthritis (SJIA) and adult onset Still’s disease are rare diseases of unknown etiology that share several clinical and laboratory features. The pathogenesis of these two diseases is complex and multifactorial, with an important role of innate immunity: activation of neutrophils and macrophages and increased levels of cytokines dependent on the activation of the inflammosome. A proportion of these patients will develop a Macrophage activation syndrome (MAS), a serious and life-threatening complication. Objectives: To identify immunological markers that allow a differential diagnosis between patients with inactive SJIA, active SJIA or MAS. To evaluate if there are differences between biomarkers in SJIA and adult onset Still’s disease Methods: Observational, prospective and multicenter study. Inclusion criteria: patients with SJIA or adult onset Still’s disease, followed in Paediatric or Adult Rheumatology Department from 5 Madrid hospitals. Group 1: Patients with active SJIA or adult onset Still’s disease +/- diagnosis of secondary MAS at the first visit, have been followed-up performing a second clinical and analytical visit at 3 months. Group 2: Patients with inactive SJIA or adult onset Still’s. Clinical and analytical data were collected, PBMCs were obtained before and after treatment, and several leukocyte subtypes were evaluated by flow cytometry (FACS). The intracytoplasmic expression of TNF-α, IL-1b and IL-6 in monocytes was determined by flow cytometry before and after stimulation with lipopolysaccharides (LPS) in the presence of monensin (Golgi inhibitor). In addition, IL-18 levels were determined by ELISA in all visits. Results: A total of 25 patients were included (18 SJIA and 7 adult onset Still’s diseases), 2 of them being excluded from the analysis because exclusions criteria. 30,4% patients presented MAS at the first visit (5 SJIA and 2 adult onset Still’s disease) and other 2 at some time during the disease. The median of IL-18 was 296.1 (CI 108.3-346.0) in patients who have never had MAS and 899.85 (CI: 397.32-1095.6) in the other group. Patients with active MAS had a CD4/CD8 ratio close to the lower limit (1.1 +/- 0.1 SD) reflecting a decrease in the CD4 + population and an increase in CD8 +. On the other hand, the rest of the groups presented a CD4/CD8 ratio of 2.6 +/- 0.5 SD in patients without disease activity and 2.0 +/- 0.7 SD in patients with active SJIA or adult onset Still’s disease but without MAS. No significant differences were found between patients with SJIA or adult onset Still’s disease. Conclusion: The results of this study show that the analysis of three determinations:%CD4,%CD8 and the CD4/CD8 ratio can help in the early detection of patients with MAS secondary to SJIA or adult onset Still’s disease. The determination of IL-18 has been in our study a marker of MAS, similar to several published studies. No significant differences were found in the immunological tests between patients with SJIA and adult onset Still’s disease with active or inactive disease. Reference: [1] Weiss ES et all Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome. Blood. 2018 Mar 29;131(13):1442-1455 Disclosure of Interests: None declared

Background: The pathological class of lupus nephritis (LN) may change to a different class during the course of the disease. Renal biopsy is repeated is repeated in many patients during a flare but there is there is no agreement about systematically recommending them because proliferative lesions on their original biopsy rarely switch to a pure nonproliferative nephritis during a flare. However, renal rebiopsy may be useful in some cases to make appropriate adjustments or changes of treatment. Objectives: To analyze the impact of renal rebiopsy on the therapeutic approach in patients with previous histological diagnosis of LN who experience a worsening in the clinical parameters of renal involvement. Methods: Retrospective study of patients with histological diagnosis of NL subjected to at least one renal biopsy. We studied the demographic, clinical, histopathological variables of the first and subsequent renal biopsies, received treatment and the therapeutic modifications in relation to the result of the rebiopsies. Results: We analyzed 35 patients diagnosed with LN between 1978 and 2017. 9 of them had been rebiopsied at least on one occasion and made a total of 11 rebiopsies (7 patients with a rebiopsy and 2 patients with 2 rebiopsies). All patients were female and Caucasian, except for a Hispanic woman, with a mean age at the time of the rebiopsy of 31 ± 12 years (14-55). The mean serum creatinine at the time of the first re-biopsy was 0.8 ± 0.17 mg/dl (0.5-1.06) and in the second, 1.18 ± 0.05 mg/dl (1.15-1.23). The fundamental indication for the rebiopsy was the increase in proteinuria, up to non-nephrotic range in 64% of the patients and within the nephrotic range in 36%. In comparison with the previous biopsy, 3 of the rebiopsies (27%) showed evolution from a non-proliferative to a proliferative form (from II to III, from II to IV and from V to V + IV). 4 of the rebiopsies (36%) started from a proliferative class and changed class but within these forms (3 from IV to III and and 1 from III to IV). The remaining 4 rebiopsies (27%) showed no change in the histological type. Regarding the baseline biopsy, we observed a decrease in the index of activity of the rebiopsies (5.4 ± 2.2 vs 3.4 ± 2.5, p = 0.017) and an increase in the chronicity index (0.8 ± 0.7 vs 2.9 ± 3.2, p = 0.027). In all cases, therapeutic modifications were carried out. In 9 cases (82%) the immunosuppression was increased and in two of them (18%) it was decreased. Conclusion: The repetition of renal biopsy in cases of LN with clinical data of renal deterioration is relevant. The change of histological class and the evolution of activity and chronicity indexes support the decision to increase immunosuppression and are fundamental to diminish it. References [1] Narvaez J, et al. The value of repeat biopsy in lupus nephritis flares. Medicine (Baltimore). 2017;96:e7099. Disclosure of Interests: None declared

Background:Biological therapy (BT) has changed the treatment and perspectives of JIA patients but little is known about when is the best moment to start BT and the impact of this prompt iniciation.Objectives:To analyze the response to BT of Juvenile Idiophatic Arthritis (JIA) patients according to the time when the BT was started.Methods:A retrospective, descriptive study was conducted on JIA patients followed up in a referal hospital that started BT up to 24 months after diagnosis from 2000 to 2018. Disease activity was measured, at 2 years after diagnosis, according to Wallace criteria for remission (absence of: active arthritis, active uveitis, fever, rash or any other manifestation attributable to JIA, normal CRP and ESR, PGA indicating no active disease) for at least 6 months.Results:55 JIA patients that started BT up to 24 months from diagnosis were analyzed. 69,1% were girls with a median age at diagnosis of 8 years old IQR(3-13), median age at the start of BT of 9 years old IQR(3-13). Regarding JIA categories: 25,5% were Oligoarticular Persistent (OligP), 18,2% Systemic JIA (sJIA), 16,4% Entesitis related Arthritis (ERA), 12,7% Psoriatic Arthritis (APso) and Polyarticular RF- (PolyRF-), 5,5% Oligoarticular Extended (OligE) and Polyarticular RF+ (PolyRF+), 3,6% Undifferentiated (Und). 20% of patients had uveitis during followup. Conventional DMARD (cDMARD) was indicated in 83,6% of patients (95,7% Methotrexate) at diagnosis [median 0 months IQR(0-2,3)]. At the end of followup (2 years) only 30,9% of patients continued with cDMARDs. The main causes of discontinuation were: adverse events (46,7%), remission (36,7%). TNF inhibitors were precribed in 81,8% of patients and 18,2% of patients recieved two BT during the first 2 years from diagnosis. 54,5% of BT were indicated during the first 6 months from diagnosis, 27,3% from 7 to 12 months, 12,7% from 13 to 18 months, 5,5% from 19 to 24 months.After 2 years from diagnosis, 78,2% of patients were on remission and 21,8% active. Among patients with active disease: 75% had arthritis, 16,7% had uveitis and 8,3% had both. There were no differences regarding disease activity among patients with uveitis and neither taking cDMARDs. Regarding JIA categories: 66,7% of OligE, 57,1% of PolyRF- and 57,1% of APso patients were active at 2 years from diagnosis when compared to the other categories (p=0.004).Patients on remission at 24 months from diagnosis started sooner the BT than active patients [CI 95% (0,46-8,29) p=0,029]. The time when the BT was started was correlated to the activity at 2 years (K= 0,294 p=0,029). When the BT was prescribed after 7,5months from diagnosis it was correlated, in a COR curve, with a higher probability of active disease at 2 years (S= 0,67 E= 0,63). There was a correlation, among patients on remission at 2 years, between prompt start of BT and less time to reach remission (K= -0,345 p=0,024). Patients with active disease at 2 years, regardless of moment of BT iniciation, required more BT during follow-up (p=0,002).Conclusion:Prompt iniciation of BT was correlated with a better outcome. JIA patients that started BT early after diagnosis had a higher probability of remission after 2 years. Starting BT after 7,5 months was correlated with a higher probability of active disease at 2 years. Active disease at 24 months was correlated with persistent active disease during follow-up.Disclosure of Interests:None declared

Background:Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of pediatric diseases. Different response to biological treatment (BT) has been reported according to disease subtype.Objectives:To analyze the prescription and withdrawal of BT in JIA patients with focus on JIA category.Methods:A retrospective observational study was conducted on JIA patients followed in a referal hospital and who had received at least one BT between 1999 and 2019.Results:130 JIA patients were analyzed: 29 (22,4%) were Oligoarticular Persistent (OligP), 22 (16,9%) Enthesitis related Arthritis (ERA), 20 (15,4%) Systemic (sJIA), 19 (14,6%) Polyarticular RF- (PolyRF-), 14 (10,8%) Polyarticular RF+(PolyRF+), 13 (10%) Oligoarticular-Extended (OligE), 11 (8,4%) Psoriatic Arthritis (APso) and 2 (1,5%) Undifferentiated (Und).The main characteristics are summarized in table 1.The first line BT most frequently indicated was Etanercept up to 40% in all the categories except for ERA, where the most frequent BT was Adalimumab and sJIA, where the most frequent BT was Anakinra. The time between diagnosis and start of BT was different among the categories (p=0,007). In the Und category, the time until BT was the shortest (median: 1 month), since both patients had coxitis, followed by APso [median: 9 months IQR(1-57)] and sJIA [median: 17,5 months IQR(0,3-146,8)].The survival of the first BT was different among the categories (p=0,006): 94,7% of the ERA continue receiving the first BT, followed by 76,2% of OligP and 50% of PolyRF+ and APso. Only 42% of sJIA continue on the first BT prescribed [up to 53,3% were TNF inhibitors (TNFi)]. The categories with less retention of the first BT were: OligE (25%); PolyRF- (27,3%) and Und (0%). The most frequent cause of discontinuation, among these categories, was secondary failure.In the survival analysis between categories, there were differences on OligP (p=0,004), OligE (p=0,042) and PolyRF- (p=0,017). Tocilizumab and Adalimumab were the BT with highest survival with regards to Infliximab, Etanercept, Rituximab (OligE, PolyRF-), Abatacept (OligE, PolyRF-) and Certolizumab (OligP). The survival rate of IL1 inhibitiors and IL6 inhibitiors was higher regarding to TNFi in sJIA patients (p=0,013).Conclusion:Taking into account JIA category is mandatory to choose BT and to understand the response and discontinuation of BT. OligE and PolyRF - showed a high rate of change of the first BT related to secondary failure of Etanercept and Infliximab when compared to Adalimumab and Tocilizumab, as described in the survival analysis. The category with the highest retention of the first BT was ERA. UND patients started sooner BT due to the presence of coxitis. In sJIA, IL1 inhibitors and IL6 inhibitors were superior to TNFi in the survival analysis, as reported in existing literature.Table:Disclosure of Interests:None declared

Background:Patients with Rheumatoid Arthritis (RA) ≥65 years old constitute an important and not very well studied group. Even though the course of the disease may be similar to that of younger patients, treatment is usually less aggressive given the limited information on efficacy, especially of biological treatments, in this age group.Objectives:To describe the characteristics of patients with RA ≥65 years old who started a second biological agent. To compare the survival of this second-line treatment between patients ≥65 and Methods:Retrospective, observational and longitudinal study. Patients diagnosed of RA, who started a second biological agent between 2000 and 2019, who discontinued a first-line TNF inhibitor, were included. Demographic, clinical and analytical data were obtained. The sample was divided in 2 groups: Results:157 patients were identified, 42 (26.8%) were ≥65 years old. In this group, 73.8% were women, with a mean age at the beginning of second biological treatment of 71.43±4.76 years. Demographic and clinical data of ≥65 years old patients are shown in the table. The most frequent second biological agent was Rituximab (23.8%), followed by Adalimumab (21.4%) and Tocilizumab (19%). 76.2% of patients had a disease-modifying drug associated, being Methotrexate the most frequent (45.2%). Discontinuation of second biological agent occurred in 30 patients (71.42%) ≥65 years old, which is similar to the percentage found in patients Conclusion:The survival of second biological agent after the failure of a first TNF inhibitor in patients ≥65 years is similar to the survival in younger patients, although there was a higher percentage of adverse effects in the first group. Rituximab and Abatacept showed a higher survival in patients ≥65 years. Smoking, erosions and diabetes mellitus were associated with an increased risk for the withdrawal of the second-line biological therapy.References:[1]Richter M, Matteson E, DavisIII J, Achenbach S, Crowson C. Comparison of Biologic Discontinuation in Patients With Elderly-Onset Versus Younger-Onset Rheumatoid Arthritis. ACR Open Rheumatology. 2019; 1(10): 627–631.Variablesn= 42 (mean ± SD or %)Age at diagnosis (years)56.48 ± 9.94Age at the beginning of the treatment (years)71.43 ± 4.76Women31 (73.8%)Smokers11 (26.2%)RF (+)35 (83.3%)ACPA (+)30 (71.4%)Erosions29 (69%)Arterial hypertension21 (50%)Diabetes mellitus4 (9.5%)Dyslipidemia11 (26.2%)Disease-modifying drugMethotrexate19 (45.2%)Leflunomide10 (23.8%)Sulfasalazine1 (2.4%)Hydroxychloroquine0 (0%)InfectionsRespiratory infection3 (7.1%)Skin/Soft tissues infections2 (4.8%)Herpes zoster1 (2.4%)Disclosure of Interests:None declared

Background:Several studies have proposed that the immunosenescence of elderly patients with Rheumatoid Arthritis (RA) in treatment with biological therapies could eliminate the need for concomitant immunosuppression with disease-modifying drugs (DMARDs), due to a probable lower production of anti-drug antibodies; however, the evidence is limited.Objectives:To compare the characteristics of patients with RA who started a second biological agent, according to age groups. To analyse second biological agent survival and its relationship with DMARDs.Methods:Retrospective, observational and longitudinal study. Patients with RA who started a second biologic between 2000 and 2019, who discontinued a first-line TNF inhibitor, were included. Demographic, clinical and analytical data were obtained. The sample was divided in 2 groups: Results:156 patients were included. 83.3% were women, with a mean age at the beginning of second biological treatment of 54.64±13.54 years. 22 patients (14.1%) were ≥70 years. Comparative analysis is detailed in table 1: patients ≥70 years presented a longer time from diagnosis to the start of biological treatment, and a higher prevalence of hypertension and diabetes mellitus. The main cause of withdrawal in this group was adverse events (46.67%) while in younger patients was treatment failure (25.27% primary failure, 29.66% secondary failure). The most frequent biological agent in ≥70 years was Rituximab (27.26%) while in Table 1.Variable≥70 years = 22 (mean ± SD or %)pAge at diagnosis (years)40.5 ± 12.358.8 ± 8.9Age at the beginning of the treatment (years)51.28 ± 11.4475.14 ± 3.5Time since diagnosis (years)10.65 ± 8.2016.27 ± 9.090.003Women113 (84.33%)17 (77.27%)0.373Smokers29 (21.64%)2 (9.09%)0.320Rheumatoid factor positive109 (81.34%)17 (77.27%)0.770Anti-CCP positive114 (90.48%)14 (82.35%)0.390Erosions92 (70.23%)16 (76.19%)0.576Arterial hypertension28 (21.37%)14 (66.67%)Diabetes mellitus3 (2.24%)4 (18.18%)Retirement91 (67.91%)15 (68.18%)0.980Infections10 (7.46%)3 (13.64%)0.397Second biological agent withdrawal causePrimary failure23 (25.27%)3 (20%)0.242Secondary failure27 (29.66%)3 (20%)Adverse events25 (27.47%)7 (46.67%)Remission2 (2.20%)0 (0%)Exitus3 (3.30%)0 (0%)Neoplasia3 (3.30%)0 (0%)Table 2.Disease-modifying drug≥70 years oldpMethotrexate72 (53.73%)9 (40.91%)0.667Leflunomide22 (16.42%)5 (22.73%)Sulfasalazine2 (1.49%)1 (4.55%)Hydroxychloroquine6 (4.48%)0 (0%)At least two of the above7 (5.22%)1 (4.55%)Conclusion:DMARD concomitant treatment has been related to a higher second biological treatment survival. This beneficial effect was not observed in RA patients ≥70 years of age whose second biological agent withdrawal cause was failure. In this age group, withdrawal related to adverse events was more frequent.References:[1]Kalden JR, Schulze-Koops H. Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment. Nature reviews Rheumatology. 2017;13(12):707-718.Disclosure of Interests:None declared

Background:Biological treatment (BT) has changed perspectives of JIA patients. Increasing data from real life experience have been reported.Objectives:To compare drug survival, safety and efficacy of BT in patients with Juvenile Idiopathic Arthritis (JIA).Methods:A retrospective observational study was conducted on JIA patients followed in a referal hospital and who had received at least one BT between 1999 and 2019.Results:218 BT in 130 JIA patients were analyzed. 67.7% were women with a median age at diagnosis of 8 years old IQR (3-13) and a median age at the beginning of the BT of 15 years old IQR(7.8-21). 21.5% of the patients had uveitis during follow-up. BT were indicated due to: arthritis(73.9%), uveitis(10.1%), arthritis and uveitis(2.7%), systemic activity(8.3%) and macrophage activation syndrome (1,8%).There were 130 BT started in 1st line, 55 in 2nd line, 20 in 3rd line, 10 in 4th line and 3 in 5th line.The 1st line BT most frequently indicated was Etarnecept(ETN) up to 40%, followed by 30% Adalimumab(ADA) and 16,2% Infliximab(INF). The median duration of the 1st line was 51 months IQR (14-109,3). However, 53.8% of the 1st line BT were swiched: 28.3% due to adverse events, 25.7% due to 1° failure and 25.7% due to 2° failure. The BT that were discontinued were: INF (76.2%) and Anakinra (ANAK) (75%) due to adverse events and ETN (59.6%) due to 1° and 2° failure. 55 patients started a 2nd BT: 43.6% received ADA and 20% Tocilizumab (TCZ) with a median duration of 43 months IQR (12-90). 22 of 55 BT required a change: 75% of ETN and 59% of INF prescribed in 2nd line were discotinued. The causes were: 40% 1° failure, 28% 2° failure and 12% remission. In 1st line 87,6% of patients received TNF inhibitors, 74% mantained the target in 2nd line. In 3rd line TCZ was the most frequent BT. 71.5% of patients continue on BT. BT was withdrawn in 20 of 130 patients due to remission (40%), adverse events (30%), and pregnancy (10%).In the analysis by decades, 80 BT (36.7%) were started from 1999 to 2008 and 138 BT (63.3%) from 2009 to 2019. In the 1st decade ETN and INF were the most frequently prescribed and in the 2nd decade, ADA and TCZ (p In the survival analysis, TCZ and ADA were the BT with the highest survival (p=0.001). Of the 31 patients that started TCZ, 61.3% continue on TCZ, with a median duration of 46 months IQR(25-99) and 36/68(52,9%) still on ADA with a median duration of 61,5 months IQR(30.5-98).Conclusion:42.3% of patients required more than one BT. Since the onset of the BT there has been a change in prescription, probably related to the emerge of new targets and the evidence provided by clinical trials and guidelines. TCZ and ADA were the BT with the highest survival rate. On the other hand, INF and ANAK were the ones with the lowest survival rate. The most common causes of BT change in 1st line were adverse events in relation to INF and ANAK. In 2nd line there was a high rate of change in those patients who maintained TNFi, related to 1° failure.Disclosure of Interests:None declared

Background Immune checkpoint inhibitors (ICI), a type of immunotherapy which block negative co-stimulation of T-cells, have surfaced as an important alternative of treatment for advanced malignancies. Unfortunately, these agents have been associated with immune-related adverse events (irAE). Objectives To analyse the frequency, type and outcome of irAE in Spanish patients treated with ICI. Methods We carried out a retrospective, observational and longitudinal study, including adult patients diagnosed with cancer and treated with ICI followed in our centre (Spanish university hospital) from October 2012 to December 2017. Demographics, clinical, therapeutic and outcome date were collected from their medical records. Results We included 125 patients, 66.4% males, all them Caucasians, with a mean age at diagnosis 63 years (range:42–81). The most common types of cancers were lung carcinoma (61.6%) and melanoma (12.8%). The ICI most frequently used was nivolumab (29.6%), followed by pembrolizumab (8.8%) and atezolizumab (8.8%), as monotherapy. It was also common, combinations, or the use of consecutive way with different drugs. Occurrence of irAE was reported in 51 patients (table 1) and the systems more frequently involved were gastrointestinal tract, endocrine glands and skin. Most of these cases were treated steroids at high doses but a case of colitis required infliximab. Withdrawal of immunotherapy was required in almost half of the adverse events (45%). During the follow-up period there were 5 deaths associated with irAE. Conclusions The frequency and type of irAE associated ICI in our series were similar to those reported in previous studies, except for rheumatological events, being arthritis and sicca syndrome the most frequently reported in other series. These adverse events are not rare and may be a potential cause of morbity in these patients, so it is important to recognise them early and treat properly, with the rheumatologist being one of the specialists involved. Disclosure of Interest None declared