No abstract

Background:In ankylosing spondylitis (AS) patients with lack of response to a first line of biologic disease modifying antirheumatic drugs (bDMARD), switching to another bDMARD is recommended, aiming either to the same or different therapeutic target. In several previous studies a decrease in drug survival has been noted when tumor necrosis factor alfa inhibitors (TNFai) are used as second or third treatment line (1,2).Objectives:Primary endpoint: To evaluate survival of bDMARD as second line treatment in patients with AS non responding to TNFai either because of lack or loss of efficacy. Secondary: To evaluate the impact on drug survival of several variables such as sex, HLA, peripheral arthritis, radiologic sacroiliitis, CRP, BASFI, BASDAI or bDMARD class.Methods:Observational, longitudinal and retrospective observational study. We included 67 patients diagnosed with AS who received treatment on second line with bDMARD (TNFai or anti IL7) after discontinuation of TNFai as first line of treatment. We analyze patients older than 18 yo, with at least 3 months of continuous treatment before and after switch, seen in our Hospital from 2006 to 2019. Data were collected regarding to demographics, HLA B27 positivity and functionality and activity index, CRP and treatment with cDMARDs.Results:All 67 patients included were still on follow up after switching to second bDMARD. Median age was 37 yo, 56.7% were male and 31%, smokers. 35.8% patients had axial AS; 1.5% peripheral arthritis; 62.7%, mixed and 9%, dactilitis. 76.1% had radiographic sacroiliitis and 74.6%, HLA B 27+. As first bDMARD, the most common was Infliximab (IFX) (47.8%), followed by Adalimumab (ADA) (19.4%) and Etanercept (ETN 14.9%). Mean survival was 32.4 months (IFX, 37 months; ETN, 45; Golimumab, 32.3 and ADA, 24.1). The commonest cause of treatment suspension was loss of efficacy (LoE) (56.7%), followed by lack of efficacy (LaE) (17.6%) and adverse effects (AE) (16.4%).As second bDMARD the most frequent was ADA (35.8%), followed by ETN (34.3%), Golimumab (9%), IFX (7.5%) and Secukinumab (6%) with a mean survival of 45 months (ETN 63.8, ADA 45.7, Golimumab 32). Treatment was discontinued in 47.8% of patients because of LoE (17.9%), LaE (17.9%) and EA (11.9%). A total of 16 AE were recorded, of which 6% were infections and 9%, allergic reactions. Regarding the analysis of the impact of other variables on drug survival, there was statistically significant differences on HLA B 27 carrier status (p=0.012), in which we observed an increase on survival when the patient is HLA B27 + and in whom BASDAI is higher before switching (p=0.02).Conclusion:In our study, we did not observe differences in survival of second line bDMARD in patients with AS regarding type of TNFai, case of discontinuation or type of radiographic involvement in the first line of treatment. Patients with HLA B27+ and high value of BASDAI at the beginning of second bDMARD showed an increased on drug survival. Contrary to literature, we did not see significant differences regarding CRP.References:[1]Glintborg B, Østergaard M, Krogh NS, Tarp U, Manilo N, Loft AGR, et al. Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor α inhibitor therapy: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2013 Jul;72(7):1149–55.[2]Deodhar A, Yu D. Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis. Semin Arthritis Rheum. 2017 Dec;47(3):343–50.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: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: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 <0.0001). The 1st BT in the 2nd decade were indicated sooner compared to the 1st decade (1st decade: mean 119.5months SD(109.2); 2nd decade: mean 53.9 months SD(99.7); p <0.0001). In 1st line BT, the BT prescribed in the 2nd decade had a shorter duration than those in the 1st decade (1st decade: mean 84.1 months SD(71.8); 2nd decade: mean 51.7 months SD(5); p <0.0001).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