No abstract

Background:The Hemophagocytic Syndrome (HPS) had a mortality rate between 20% and 90%. The mortality of HPS secondary to autoimmune diseases (AID) is lower than hemato-oncological diseases (HOD). In general, the HOD, thrombocytopenia, age, and a prolongation of prothrombin are considered to be an adverse prognostic factor.(1)Objectives:To describe and identify differences between patients who survived and did not survive to HPS during hospital admission to a tertiary hospital between 2005 and 2019.Methods:This is a retrospective observational study. All patients who met the diagnostic criteria for LHH were included, or who presented haemophagocytic cells in the bone marrow biopsy, or who had diagnosis of HPS in the hospital discharge report.(2) Demographic, clinical, analytical, etiological, underlying disorder and prognosis variables were collected. Continuous variables are described with the mean or median according to the degree of normality. Kruskal Wallis, Fisher test and Mann-Whitney U test were used for the bivariate analysis, and also a multivariate logistic regression analysis was performed.Results:Thirty patients with HPS were included. They were distributed in 5 subgroups (Table 1). Overall mortality was 43.3%, statistically significant higher in the HOD [8 patients (66.7%); p 0.029]. Also, they were divided into 2 groups (survivor vs. non-survivor; Table 2). In the multivariate model the age and INR prolongation were confirmed to be independently associated with the outcome of mortality.Table 1.Etiology of HPSEtiologyn = 30MortalityAID10n = 1 Systemic lupus erythematosus51 Adult Still’s Disease3No Rheumatoid arthritis1No Sclerosing Disease IgG41NoHOD12n = 8* Non-Hodgkin’s lymphoma31 Myelodysplastic syndrome32 Acute leukemia33 Extranodal NK cell lymphoma11 Multiple Myeloma1No Probable lymphoproliferative process11Infectious diseases2n = 1 Pneumocystis carinii in patient with H.I.V.11 Campylobacter yeyuni1NoGlyoblastoma multiforme with temozolomida1n = 0HPS without defined aetiology53HIV: Human Immunodeficiency Virus, NK: Natural Killer. *p = 0,029Table 2.Characteristics and differences between survivor and non-survivor groupsTotalNon-survivorsurvivorn301317p<0,05Age55,5±18,36858,2-74,54034-570,043Women1653,3%761,5%947,1%1,00Comorbidities (≥ 2)516,7%215,4%317,6%1,000Hospital stay35,520-60,82915,5-39138-170,563Splenomegaly1653,3%753,8%952,9%1,000Hepatomegaly1033,3%538,5%529,4%0,705Hb (g/dL)7,16,4-7,9710%6,2-7,87,16,6-7,80,094Pt (x109/L)13 5005 000-52 50016 00011 000-44 00012 0005 000-99 0000,281Pt≤ 100 0002583,3%13100%1270,6%0,052Leu (x109/L)1 250238-3 1531 300150-3 9401 400200-3 3400,457Neu (x109/L)6150-1 5501 29020-3 3006500-1 4000,805Fb (mg/dL) (n=24)171111-358167,00106-253169,00103-4510,796Fer (ng/mL) (n=28)15 3305 434-38 28429 0635 728-74 60413 2258 287-28 7290,108Tg (mmol/L)341226-438254,00184-382471,00341-6040,053GOT (U/L)13977,5-406,3133,00101-513179,00101-512,50,483GPT (U/L)16246-389109,0041-333199,0099-2980,198INR (n=29)1,51,1-1,92,11,2-3,71,51,1-1,60,028Hb: Hemoglobin, Pt: platelets, Leu: leukocytes, Neu: neutrophils, Fb: fibrinogen, Fer: ferritin, Tg: triglycerides, GOT: aspartate aminotransferase, GPT: alanine aminotransferaseConclusion:The HOD presented higher mortality. The non-survivor group presented a longer INR prolongation and a higher age at the time of diagnosis.References:[1]Parikh SA. Prog. factors and outcomes of adults with HLH. Mayo Clin Proc. 2014;89:484–492.[2]Henter JI. HLH-2004: Diag. and therapeutic guidelines for HLH.Pediatr Blood Cancer. 2007;48:124.Disclosure of Interests:César Antonio Egües Dubuc: None declared, Andrea De Diego: None declared, Patricia Cabrera Miranda: None declared, Nerea Alcorta Lorenzo: None declared, Jesús Alejandro Valero Jaimes: None declared, Jose Ramon Furundarena Salsamendi: None declared, Olga Maiz-Alonso: None declared, Luis Maria Lopez Dominguez: None declared, Esther Uriarte Isacelaya: None declared, Jorge Jesús Cancio Fanlo: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Joaquin Maria Belzunegui Otano: None declared

BackgroundUpadacitinib (UPA) is an inhibitor of JAK kinases recently approved by EMA for the treatment of psoriatic arthritis (PsA) in Europe (January 2021)[1]UPA has shown efficacy in refractory patients to anti-TNF[2]ObjectivesA) to assess efficacy and safety of UPA in the first cases in Spain in clinical practice.B) to compare the profile of clinical practice (CP) patients with clinical trial (CT) of UPA in PsA refractory to biologics[2]MethodsStudy of 101 patients of CP with PsA treated with UPA in Spain. The diagnosis of PsA was made using CASPAR criteria. Patients who received one or more dose of UPA with at least one follow-up visit were included. Results are expressed as percentage, mean±SD or median [IRQ]Results101 patients (73♀/28♂), mean age of 43.8 ± 12.1 years(Table 1).Pattern joint involvement was: peripheral (n=61) axial (8) and mixed (32) During the PsA evolution patients presented enthesitis (38.6%) nail involvement (22%) and dactylitis (25.7%)Prior to UPA most patients (71.3%) received oral prednisone or equivalent (mean maximum dose 12.04±6.98 mg/d), synthetic immunosuppressants (mean; 1.8±0.9) and biological therapy (TB) (3.4±2.2). TB were: etanercept (n=47), adalimumab (77), infliximab (23), golimumab (21), certolizumab (32), secukinumab (53), ixekizumab (32), ustekinumab (34), Abatacept [2], brodalumab [1] and guselkumab [2]. Apremilast was used in 23, Tofacitinib in 26 and filgotinib in 1UPA was started (15 mg/24 h) after a mean follow-up of 9.9±7.8 years from PsA diagnosis. Prednisone was used in 47 cases (mean dose, 7.8±5.7 mg/d). UPA was combined with methotrexate (n=30), salazopyrin (7) and leflunomide (15); in the remaining 51 cases (50.50%) was used in monotherapy. At UPA initiation patients presented peripheral arthritis (78%), axial involvement (28,71%), skin involvement (22.8%), enthesitis (22.7%), and dactylitis (11%)Patients of CP compared with CT were younger, more frequently women, refractory to a greater number of TB and received more concomitant corticosteroid(Table 1)After a median follow-up of 5.72±4.64 months with UPA, patients showed a prompt improvement in activity indexes (DAS28, DAPSA)(Figure 1) and CRP mg/L decreased from a median 2.51 [1.0-8.0] to 1.00 [0.30-5.00] (p <0.006). Extra-articular manifestations also improved: dactylitis in 75% patients, enthesitis (55.56%) and skin involvement (60%)No serious Adverse events (AE) were reported. Minor side effects were observed in 20 patients (19.8%). UPA was discontinued in 31 (20 inefficiency, 4 patient decision, 2 infection, 2 thrombosis, 1 surgery, 1 pregnancy)ConclusionIn this study, first patients of CP in Spain with UPA in PsA were younger, received concomitant corticosteroid more frequently and were refractory to a greater number of TB than those of CP. As in the UPA CT, it seems effective, rapid and relatively safe in daily CP for refractory Ps.A.References[1]https://www.ema.europa.eu/en[2]Mease PJ et al. Ann Rheum Dis 2021;80:312–320Table 1.CLINICAL PRACTICE N=101CLINICAL TRIAL N=211pBaseline demographic parametersAge years (mean±SD)43.8±12.153.0 ± 12.0<0.001Sex n (%) female73 (72.3)113 (53.6)0.002Disease CharacteristicsDuration of PsA year (mean±SD)9.94 ± 7.89.5 ± 8.40.658HAQ-DI0.97±0.651.10 ± 0.60.082Swollen joint count mean±SD4.33 ± 5.0111.3 ± 8.2<0.001Painful joint count mean±SD6.15 ± 5.6824.9 ± 17.3<0.001Enthesitis n (%)23 (22.7) MASES172 (81.5) SPARCC<0.001Dactylitis n (%)11 (11)55(26.1)0.001PASI score mean±SD0.95±1.6410.1 ± 9.2<0.001CRP (mg/L)8.72 ± 15.5011.2 ± 18.50.245Oral glucocorticoid use n (%)47 (46.53)22 (10.4)<0.001Concomitant synthetic DMARDs n (%)50 (49.50)98 (46,4)0.613Previous use of biological DMARDs n (%)94 (93.1)195 (92.4)0.837Number of prior failed biologic DMARDs n (%)116 (15,84)135 (63.7)<0.001218 (17.82)35 (16.5)0.786≥360 (59.40)24 (11.3)<0.001UPA in monotherapy n (%)51 (50.50)113 (53.6)0.613HAQ-DI Health Assessment Questionnaire-Disability Index, PASI Psoriasis Area Severity Index, CRP C-reactive protein, DMARD disease-modifying antirheumatic drugFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Apremilast is a non-biologic systemic agent approved for the treatment of plaque psoriasis, oral ulcers of Behcet’s disease and PsA with proven efficacy in clinical trials [1,2]. However, more real-world evidence of apremilast use and effectiveness is needed to identify the patient profile most likely to benefit from this treatment [3].Objectives:To evaluate the persistence of apremilast treatment in patients with PsA naïve to biological treatments in routine clinical practice and assess its effectiveness. Baseline clinical characteristics on patients who started apremilast were also evaluated.Methods:Observational, prospective, multicenter (20 centers) study including consecutive adult patients with PsA naïve to biological therapies who had started treatment with apremilast during the previous 5 to 7 months and were followed-up during 12 months. Variables recorded were persistence of treatment with apremilast at 6 months (6mo) and number of swelling joints, presence of enthesitis and dactylitis, and disease activity, measured by the Disease Activity in Psoriatic Arthritis (DAPSA) score and Physician Global Assessment (PGA) of psoriasis, collected at baseline (BL) (i.e., apremilast treatment start) and 6mo; comorbidities were retrospectively collected at BL. Categorical and quantitative variables were compared using McNemar’s and Wilcoxon test, respectively. Data sets analyzed included all assessable patients.Results:Of the 60 patients recruited at the time of this interim analysis, 54 (90.0%) [mean (SD) age 53.4 (13.9) years] were assessable; 41 (75.9%) of these continued treatment with apremilast at 6mo. At BL, 34 (63.0%) patients had at least one comorbidity, the most frequent being cardiovascular disease (n=15, 27.8%), including hypertension (n=8, 14.8%), metabolic/endocrine disease (n=18, 33.3%), including obesity (n=8, 14.8%) and dyslipidemia (n=10, 18.5%). Psychiatric disease (i.e., depression) (n=5, 9.3%) and neoplasia (n=8, 14.8%) were also observed. The number of swelling joints decreased from median (Q1, Q3) 4.0 (2.0, 7.0) at BL to 1.5 (0.0, 4.0) at 6mo (p=0.0012). Patients with dactylitis and enthesitis decreased from 19 (35.2%) and 16 (29.6%) at BL to 10 (18.5%) and 9 (16.7%) at 6mo (p=0.0225 and p=0.0391), respectively. The distribution of patients in the different disease activity categories according to DAPSA scale changed between BL and 6mo, indicating a favorable disease evolution (Figure 1 next page). According to PGA, at BL (n=53), disease activity was categorized as mild in 18.0%, as moderate in 72.0%, and as severe in 10% of patients and, at 6mo (n=54), as mild in 70.6%, as moderate in 25.5%, and as severe in 3.9% of patients. Fifteen (27.8%) patients interrupted treatment permanently (n=13, 24.1%) or temporarily (n=2, 3.7%), due to no/partial response (n=8, 14.8%), tolerability issues leading to adverse events (n=3, 5.6%), patient decision (n=2, 3.7%), and other reasons (n=2, 3.7%) after a mean (SD) treatment of 3.05 (2.20) months.Conclusion:Forty-one (75.9%) patients with PsA naïve to biological therapies were treated with apremilast during ≥6 months. After treatment, the number of swelling joints, and dactylitis and enthesitis decreased and changes in disease activity according to DAPSA and PGA pointed to a favorable disease evolution. Apremilast treatment provides a clinical benefit to patients with PsA treated in clinical practice.References:[1]Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016 Feb 10;75(3):499 LP-510[2]Torres T and Puig L. Apremilast: A novel oral treatment for psoriasis and psoriatic arthritis. Am J clin Dermatol. 2018 Feb;19(1):23-32[3]Coates LC, Kavanaugh A, Mease PJ et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015. Treatment Recommendations for Psoriatic Arthritis. Arthritis Rheumatol. 2016;68(5):1060– 71.Disclosure of Interests:Jordi Gratacos-Masmitja Speakers bureau: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene y Lilly., Consultant of: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene y Lilly., José Luis Álvarez Vega Speakers bureau: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Consultant of: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Grant/research support from: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Emma Beltrán Speakers bureau: Abbvie, Bristol, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: Abbvie, Bristol, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, ANA URRUTICOECHEA-ARANA: None declared., C. Fito-Manteca: None declared., Francisco Maceiras: None declared., Joaquin Maria Belzunegui Otano Speakers bureau: Lilly, Amgen, Novartis, Abbvie, Janssen., J. Fernández-Melón Speakers bureau: Amgen SL, Eugenio Chamizo Carmona: None declared., Abad Hernández Speakers bureau: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Consultant of: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Grant/research support from: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Inmaculada Ros Consultant of: Amgen, Grant/research support from: MSD, Roche, Novartis, lilly, Pfizer, Amgen, Eva Pascual Shareholder of: Amgen, Employee of: Amgen, Juan Carlos Torre Speakers bureau: Amgen, Lilly, Novartis, Janssen, Pfizer, Consultant of: Amgen, Lilly, Novartis, Janssen, Pfizer, Grant/research support from: Amgen, Lilly, Novartis, Janssen, Pfizer.

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