A possible case of sprue-like enteropathy (SLE) induced by the use of telmisartan is reported. Telmisartan is an angiotensin-receptor II blocker (type 1) used for the treatment of hypertension. Several cases of SLE associated with olmesartan and other drugs of the same group have been reported. In all cases, SLE resolved following therapy withdrawal. We describe the case of an 80-year-old woman who presented with diarrhoea and abdominal pain. In the past 5 years she had been treated with telmisartan 40 mg once a day for hypertension, so we hypothesised that symptoms might be caused by telmisartan. After treatment discontinuation, diarrhoea disappeared. Three causality algorithms were applied and revealed a possible or likely causal relationship. At present, the patient remains asymptomatic. There is a causal relationship between the use of telmisartan and SLE. This association should be taken into account by physicians when prescribing and reviewing drug therapies.

No abstract

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

Background:Tapering and withdrawal of biological DMARDs (bDMARDs) is often attempted in Juvenile Idiopathic Arthritis (JIA) patients but data about response to re-treatment after an unsuccessful tapering are scarce.Objectives:Our aim is to assess response to re-treatment after a disease flare during tapering or withdrawal of bDMARDs and to describe re-treatment strategies.Methods:A retrospective, descriptive study was conducted in a cohort of JIA patients followed up in a referral hospital and who had received bDMARDs between 2000 and 2019. All JIA patients with at least one flare during tapering or withdrawal were included. Response to re-treatment was defined as achieving Wallace criteria for remission for 6 months.Results:A total of 142 flares during tapering or withdrawal were identified and included. In 3/142 (2.1%) patients bDMARDS were not re-started after a flare, 1 due to patient refusal, 2 due to unplanned pregnancy. Main characteristics according to tapering strategies are reported in Table 1.Table 1.Main characteristics according to tapering strategies. Apso, Psoriatic Arthritis; ERA, Enthesitis related Arthritis; OligE, Oligoarticular Extended; OligP, oligoarticular persistent; Poly RF+, polyarticular rheumatoid factor positive; PolyRF-, polyarticular rheumatoid factor negative; sJIA, Systemic JIA; Und, Undifferenciated.TaperingWithdrawalCases, n (%)80 (57.5)59 (42.4)Female, n (%)57 (71.3)36 (61)Age at diagnosis,years, median (IQR)5 (2-11)4 (2-11)Age at start of tapering or withdrawal, years, median (IQR)17 (11-25)16 (8-29)Categories, n (%)OligP19 (23.8)12 (20.3)OligE15 (18.8)13 (22)sJIA10 (12.5)11 (18.6)ERA12 (15)8 (13.6)Apso7 (8.8)6 (10.2)Poly RF+9 (11.3)4 (6.8)Poly RF-7 (8.8)3 (5.1)Und1 (1.3)2 (3.4)Uveitis, n (%)24 (30)16 (27.1)Laboratory values, n (%)- RF15 (18.8)5 (8.5)- ANA45 (56.3)33 (55.9)cDMARDs at start of tapering, n (%)40 (50)20 (33.9)bDMARD target, n (%)- TNF inhibitors63 (78.8)45 (76.3)- IL6-blockers14 (17.5)5 (8.5)- IL1-blockers2 (2.5)7 (11.9)- Rituximab1 (1.3)2 (3.4)Line of bDMARD, n (%)- First50 (62.5)45 (76.3)- Second18 (22.5)10 (16.9)- Third5 (6.3)2 (3.4)- Forth6 (7.5)2 (3.4)- Fifth1 (1.3)0 (0)Time in bDMARD treatment, months median (IQR)28.4 (13.3-52.5)28.2 (13.9-44.6)Remission prior tapering or withdrawal,months median (IQR)8 (6-12)8 (6-12)Fifty-nine out of 80 (73.8%) tapering cases were on remission at 6 months (6m) and 42/80 (52.5%) at 12 months (12m). Regarding dosage schedule adjustments, interval widening was the most frequent in 70/80 (87.5%) followed by combined strategy in 7/80 (8.8%) and lower dosage in 3/80 (3.8%). Median remaining dosage administrated was 54.9% IQR(50-75). Median time to flare was 14.9 months IQR (5.6-24.7). Median time to re-start of bDMARDs was 0 months min-max(0-13).After withdrawal of bDMARDs 23/59 (39%)cases at 6m and 14/59 (23.7%) cases at 12m were on remission. Median time to flare was 4.7 months IQR (2.8-11.4). Median time to re-start of bDMARDs was 1 month min-max (1-6).Most frequent re-treatment strategies were re-start of standard dosage [tapering 42/80 (52.5%), withdrawal 34/59 (57.6%)], re-start of previous effective dosage [tapering 28/80 (35%), withdrawal 11/59 (18.6%)], change of bDMARD [tapering 6/80 (7.5%), withdrawal 6/59 (10.2), re-start of bDMARD and cDMARD [tapering 4/80 (5%), withdrawal 6/59 (10.2)] and re-start of cDMARD [tapering 0/80 (0), withdrawal 1/59 (1.7%)].Overall response to re-treatment was 75/80 (93.8%) and 53/58 (91.4%) among tapering and withdrawal, respectively. In 12/139 (8.6%) patients bDMARD was changed, achieving remission in 11/12 (91.7%) cases. No factors were associated with response to re-treatment and there were no differences between re-treatment strategies and re-achieving remission (p=0.596).Conclusion:Response to re-treatment was high (92.7%), no risk factors were identified. Most frequent retreatment strategy was re-start of standard bDMARD dosage in 76/139 (54.7%) followed up by restart of previous effective bDMARD dosage in 39/139 (28.1%).Disclosure of Interests:None declared