Background:Biological therapies have revolutionized the management of rheumatic diseases. This study analyzes the paradoxical autoimmune inflammatory manifestations that these therapies can induce. They are described as paradoxical because these are diseases in which the same biological drugs have proven effective.Objectives:The aim of this study is to carry out a descriptive analysis of paradoxical biologics-induced autoimmune manifestations.Methods:A retrospective research was carried out during January 2017 and March 2018 at Hospital Universitario Donostia.Computerized medical records were reviewed. The following variables were recorded: underlying disease; type of developed manifestation; the triggering biologic drug and its duration; concomitant treatment with disease-modifying antirheumatic drugs (DMARDs), previous biological treatments; the adopted measure and the resolution of the complication or not.Qualitative variables are recorded in absolute value and in percentage. The quantitative variables are recorded with the mean and standard deviation. The data has been analyzed with the SPSS Statistics 20 program.Results:Twenty-six cases were analyzed. The most common triggering drugs were infliximab (30.8%), adalimumab (30.8%) and etanercept (15.4%). The most common underlying diseases were spondyloarthritis (42.3%), rheumathoid arthritis (34.6%) and Crohn’s disease (11.5%). The most developed complications were cutaneous affectations (76.9%), psoriasis specifically.Statistical significative difference regarding the molecules causing the complication, has only been found in the previous use of biologic drugs (p 0.003), number of treatment dropouts (p 0.048) and number of resolved complications (regardless of the adopted measure) (p 0.041).Conclusion:Infliximab and adalimumab are the drugs that presented the most paradoxical manifestations, probably because they are the oldest and most used ones. The difference found in previously used biologics, could be due to the fact that new drugs are less frequently presented as the first option. Psoriasis is the most frequently developed complication. The difference found in the number of abandonments of the biologic treatment and the solution of the complication might be more associated with the complication itself, rather than with the responsible molecule. There is no consensus on the measures to be taken when facing the complication. The severity of the manifestation should be assessed, as well as the control of the underlying disease. Most complications resolve overtime.Table 1Infliximabn 8 (31.8%)Adalimumabn 8 (30.8%)Etanerceptn 4 (15.4%)Certolizumabn 2 (7.7%)Golimumabn 2 (7.7%)Abataceptn 1 (3.8%)Tocilizumabn 1 (3.8%)Totaln 26 (100.0%)p valueUnderlying disease0.789Rheumatic (%)6 (75.0)5 (62.5)4 (100.0)2 (100.0)2 (100.0)1 (100.0)1 (100.0)21 (80.0)Digestive (%)2 (25.0)3 (37.5)000005 (19.2)Type of developed manifestation0.235Hematologic (%)01 (12.5)000001 (3.8)Neurologic (%)2 (25.0)0000002 (7.7)Digestive (%)00001 (50.0)001 (3.8)Cutaneous (%)6 (75.0)6 (75.0)4 (100.0)2 (100.0)1 (50.0)01 (100.0)20 (76.9)Other (%)01 (12.5)0001 (100.0)02 (7.7)Table 2Infliximabn 8Adalimumabn 8Etanerceptn 4Certolizumabn 2Golimumabn 2Abataceptn 1Tocilizumabn 1Totaln 2p valueThe triggering biologic drug and its duration (months)43.25(SD 44.81)10.9375.50(SD 66.08)4.5011.006.005.0030.660.635Concomitant treatment with DMARDs (%)2 (25.0)2 (25.0)1 (25.0)1 (50.0)001 (100.0)7 (26.9)0.811Previous biological treatment (%)02 (25.0)1 (25.0)2 (100.0)2 (100.0)1 (100.0)1 (100.0)9 (34.6)0.003Suspension as the adopted measure (%)5 (62.5)7 (87.5)02 (100.0)1 (50.0)1 (100.0)1 (100.0)17 (65.4)0.048Resolution of the complication (%)3 (37.5)8 (100.0)1 (25.0)1 (50.0)1 (50.0)1 (100.0)1 (100.0)16 (64.0)0.041Disclosure of Interests:None declared

Background:Biological disease modifying drugs (bDMARD) has allowed a targeted approach to rheumatoid arthritis (RA). Once sustained remission is achieved, the use of bDMARDs at lower doses than indicated in data sheets is considered (optimized treatment, OT). Studies show that 33-64.2% of patients on OT lose remission in the first 6 months. Still, it is a feasible practice in selected patients.Objectives:We aimed to describe demographic, clinical, analytical and therapeutic characteristics of RA patients on OT in our hospital. Secondly, we wanted to study the survival of OT and to compare patients with survival longer or shorter to one year.Methods:We did a retrospective review of the medical records of RA patients who began OT between January 2014 and December 2018. We included patients on Abatacept(ABA), anti-TNF drugs and Tocilizumab (TCZ). We defined the end of OT as the restart of the usual dose. Continuous variables are described with mean and standard deviation (SD) and qualitative variables are shown in absolute value and percentage. We divided the sample into patients with OT survival greater than or equal to one year and patients with OT survival less than one year, after which the characteristics of both populations were compared. Categorical variables were analyzed using Pearsons chi and quantitative variables using Student’s t-test. Survival analysis was performed using a Kaplan-Meier estimator.Results:We identified 234 RA patients on bDMARD at our hospital, of which 53 (22.6%) had been optimized between January 2014 and December 2018: 39 (73.6%) with anti-TNF, 7 (13.2) with ABA and 7 (13.2%) with TCZ. Their characteristics are shown in table 1. It is worth mentioning the rate of monotherapy (43.3%)and the low number of bDMARD prior to optimization (median 0.71, SD 0.97). The median survival of OT was 33.8 months and thirty-nine patients (73.6%) maintained OT for at least one year (95%confidence interval, 0.59 to 0.83). When comparing patients with survival greater/equal versus shorter to one year (table 2), the only variable showing significant differences was the presence of erosions at beginning of OT (28 patients in the >1 year group vs 7 in the < 1 year group; p=0.012). Although the difference is not significant (p = 0.07), patients with a survival of less than one year had more time between the debut of disease and the beginning of the first conventional synthetic DMARD (csDMARD).Table 1.Characteristics of the sample (N=53)Female40 (75.47%)Age at diagnosis (years)49.54 (11.68)Active smoker15 (33.33%)ACPA positive36 (67.92%)mRF positive44 (83.02%)Nodules11 (20.75%)Extra-articular disease11 (20.75%)Erosions*35 (74.47%)Monotherapy at optimization23 (43.4%)bDMARD* previous to OT0.71 (0.97)Optimized bDMARD•ETN20 (37.74%)•ADA16 (30.19%)•ABA7 (13.21%)•TCZ7 (13.21%)•GOL2 (3.77%)•CZB1 (1.89%)DAS28 at•Diagnosis4.88 (1.25)•Beginning – 1st sDMARD4.62 (1.6)•Beginning – 1st bDMARD4.98 (1.06)•Beginning – opt bDMARD4.67 (1.17)•Optimization1.88 (0.65)Months from diagnosis to introduction of 1st sDMARD*19.67 (35.01)Months from disease debut to low activity*38.75 (30.34)Months in low activity until start of OT23.73 (22.47)ACPA: anti-citrullinated protein antibodies; mRF: monoclonal rheumatoid factor; Erosions: presence of erosions at Optimization; bDMARD: biological DMARD; ETN: Etanercept; ADA: Adalimumab; ABA:Abatacept; TCZ:Tocilizumab; GOL:Golimumab; CZB:Certolizumab; Opt bDMARD: bDMARD optimized; csDMARD: conventional synthetic DMARD; Low activity: DAS28 < 3.2Conclusion:OT is a therapeutic option from which some patients could benefit. Maintenance of OT may be related to early start of DMARDs. More studies are needed to define the characteristics of patients who can safely benefit from OT.References:[1]Henaux S et al. Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis. Ann Rheum Dis 2018;77:515–522.Disclosure of Interests:None declared

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Background: Hemophagocytic Syndrome (HPS) is an uncommon disorder with high mortality. HPS is reported to be usually related to some underlying conditions; autoimmune (AI) and hematological malignancies (HM) are two main underlying conditions. Here, we attempted to determine the clinical characteristics/differences of HPS according to underlying conditions; AI vs. HM, based on our experience. Methods: We studied all adult patients with HPS diagnosed at our institution from 2005 to 2019. Demographic, clinical characteristics, laboratory findings, underlying disorders, hospital stay and prognosis variables were examined and related to the underlying conditions. Results: 30 patients (median age of 55 years and male/female of 14/16) met the inclusion criteria which we analyzed: HM: 12 (40%), AI: 10 (33%), and others: 8 (27%). HM group, compared with AI group, showed a significantly longer length hospital stay (HM vs AI: 61.5 vs 30.5 (median)), more severe thrombocytopenia, leukocytopenias, and neutropenia, and importantly, higher mortality (with overall mortality and HM-related HPS-mortality being 43.3 and 66.7%, respectively). Contrarily, HM group, compared with AI group, showed less severe liver abnormalities (AST; 106 vs 457 (median): ALT; 109 vs 457 (median)). Conclusions : The HM subgroup presented a greater mortality and a higher number and severe cytopenias but lower elevation of transaminases.