Background: One of the most impacting complications of Sjögren’s disease (SjD) is the development of lymphoma, reported to occur in around 5-10% of patients with SjD. There have been multiple studies proposing possible risk factors for lymphoma in SjD. Objectives: Our goal is to assess the prevalence of lymphoma in a nationwide cohort of SjD and identify potential risk factors for its occurrence in these patients. Methods: Multicentre retrospective cohort study, including patients with a clinical diagnosis of SjD, registered in PORTRESS — the Portuguese Registry of SjD — up to November 2023. Patients with information on the presence or absence of lymphoma were included. Demographic, clinical, treatment and patient-reported outcomes (PROs) data were collected. Univariate analysis was performed using chi-square, Fisher’s exact, Mann-Whitney or t-test, and correlation between continuous variables using Pearson or Spearman, according to their distribution. Predictors of the development of lymphoma were identified through binomial logistic regression modelling. Results: A total of 846 patients were included. Hematological neoplasia was found in 24/846 patients (2.8%), most commonly lymphoma (20/846, 2.4%). The most frequent type of lymphoma was MALT lymphoma (n=7).Patients with SjD-associated lymphoma were more frequently male (p=0.030) and had a higher frequency of pulmonary (p=0.039) and renal involvement (p=0.040; Table 1). They were also more frequently treated with Rituximab (p=0.016), as expected. Both age at diagnosis and at symptom onset were non-significantly higher in the subgroup of patients with lymphoma.Known risk factors for lymphoma were present in a significant part of the cohort. Lymphopenia and low C3 were seen in 22.8 and 17.9%, respectively. Lymphadenopathies were found in 12.3% of patients. Furthermore, decreased C4 was present in 9.1%, persistent SG swelling in 8.4%, cutaneous vasculitis in 6.5% and, less frequently, monoclonal gammopathy (5.5%) and cryoglobulins (3.1%). When submitted to a salivary gland biopsy, ectopic lymphoid structures (ELS) were seen in 44/480 patients (9.2%).From the previously studied risk factors for the development of lymphoma in SjD patients, decreased C3, persistent salivary gland swelling, lymphadenopathies and ELS on the minor salivary gland biopsy were significantly more frequent in the population with lymphoma (Table 1).On multivariate analysis, persistent salivary gland swelling (OR 9.6, 95%CI: 1.5-61.9, p=0.018) and age at diagnosis (OR 1.2, 95%CI: 1.0-1.2, p=0.035) were found to be independent predictors of lymphoma, irrespective of sex, disease duration, decreased C3, lymphadenopathies and ectopic lymphoid structures on the minor salivary gland biopsy. Conclusion: The PORTRESS cohort had a lower prevalence of SjD-associated lymphoma than previously reported. Persistent salivary gland swelling was the predominant risk factor for lymphoma in our cohort. Furthermore, older age at SjD diagnosis was independently associated with the development of lymphoma. REFERENCES: NIL Acknowledgements: This project was funded by SPCare; PORTRESS Reuma.pt Task Force: Margarida Silva, Sara P Dinis, Filipe Vinagre, Maria H Lourenço, Ana B Silva, Alexandra Daniel, Paula Valente, Inês Almeida, Joana Dinis, Lígia Silva, Lídia Teixeira, Filipe Araújo, Carlos M Gomes, Patrícia Pinto, Filipa Farinha, Teresa Nóvoa, Ana Rodrigues, Sara Cortes. Disclosure of Interests: Matilde Bandeira Research grant for this registry: SP Care, Manuel Silvério-António menarini, theramex, Roberto Pereira da Costa: None declared, Ana Rita Lopes: None declared, Filipe Cunha Santos: None declared, Paulo Pereira: None declared, Diana B Raimundo: None declared, Anita Cunha: None declared, Cláudia Pinto Oliveira: None declared, Ana Catarina Duarte Boehringher Ingelheim, João Madruga Dias: None declared, Mariana Emília Santos: None declared, Maria João Gonçalves: None declared, Ana Catarina Moniz: None declared, Ana Maduro: None declared, Mariana Luis: None declared, Ana Valido: None declared, Margarida Oliveira: None declared, Catarina Tenazinha: None declared, Nikita Khmelinskii Paid instructor: GSK. Paid speaker: Astrazeneca, GSK, Vifor Pharma. Paid consultant: Abbvie, Astrazeneca, GSK, Novartis., Filipe Barcelos: None declared, Joao Eurico Fonseca: None declared, Vasco C Romão Speaking fees: Astrazeneca, Abbvie, GSK, Janssen, Lilly, Pfizer, Sobi, Research Grants: MSD, SPCare Travel grants and scientific support: Abbvie, Lilly, Medac, MSD, Novartis, Pfizer, Roche.Table 1SjD and lymphoma patientsLymphoma (n=20)SjD without lymphoma (n=826)p-valueAge diagnosis59.1±16.353.2±14.8NSAge symptom onset52.3±14.048.2±15.1NSDisease duration17.4±13.513.2±9.2NSFemale16 (80)778 (94.2)0.030Death1 (6)4 (1)NSACR/EULAR 201613 (65)557 (71)NSAnti-Ro16 (84)694 (86)NSAnti-La8 (89)364 (76)NSRF9 (50)366 (49)NSFocus score1.0±0.71.7±2.3NSHypergamaglobulinemia10 (59)361 (49)NSLow C36 (40)138 (17)0.036Low C41 (7)72 (9)NSPersistent SG swelling7 (37)62 (8)<0.001Lymphadenopathies7 (39)94 (12)0.003Cutaneous vasculitis2 (12)51 (6)NSCryoglobulinemia2 (14)15 (3)NSLymphopenia6 (33)180 (23)NSMonoclonal gamopathy2 (12)41 (6)NSEctopic lymphoid structures3 (38)41 (9)0.029InvolvementConstitutionalGlandularArticularCutaneousPulmonaryRenalMuscularPNSCNSHematologicBiologic5 (26)10 (53)8 (42)4 (21)5 (26)3 (16)0 (0)2 (11)0 (0)9 (47)13 (72)180 (23)288 (36)360 (45)173 (22)80 (10)31 (4)17 (2)31 (4)15 (2)321 (40)450 (56)NSNSNSNS0.0390.040NSNSNSNSNSSG – salivary gland, PNS/CNS – peripheral/central nervous system, NS – non-significant

Background: We recently created PORTRESS, the Portuguese registry of Sjögren’s Disease (SjD), as a specific module embedded within the Portuguese Registry of Rheumatic Diseases (Reuma.pt). Objectives: To characterise the largest nationwide cohort of SjD patients. Methods: We included patients with a clinical diagnosis of SjD, registered in PORTRESS up to November 2023. Demographic, clinical, treatment and patient-reported outcomes (PROs) data were collected. Variables were compared according to parametric or non-parametric tests, as applicable. Results: 1375 patients were included. Patients fulfilled AECG 2002 or ACR/EULAR 2016 classification criteria in 62.1% and 57.4% of cases, respectively. However, a large percentage of patients (n=769/1375, 55.9%) did not have a complete assessment of all criteria, which translates common clinical practice reality. Importantly, the vast majority of patients had both sicca symptoms (or extraglandular involvement) and a positive anti-Ro and/or minor salivary gland biopsy (n=1130/1210, 93.4%).Most patients were anti-Ro positive and almost half had circulating rheumatoid factor. Hypergammaglobulinemia (49%) and raised immunoglobulin G (40%) were common, unlike cryoglobulinemia (6%). Although Schirmer’s test, SG ultrasound and minor SG biopsy were positive in 52-59% of patients, only 22% had reduced unstimulated whole salivary flow.Most patients (88%) had at least one active ESSDAI domain over the course of the disease. Around half had laboratorial features of B cell hyperactivity (52%), whereas articular, hematologic and glandular involvements were seen in 31-43% of patients (Table 1). Excluding biological and hematological involvement, both involvements that poorly correlate with disease impact, systemic involvement was still observed in almost two thirds of patients (64%).Hydroxychloroquine and corticosteroids were used in 65% and 29% of patients, whereas 1 in 5 was treated with pilocarpine. Of note, up to 12% of patients were treated with other immunosuppressants.The mean ESSDAI was 3.0±4.4 (range 0-42), corresponding to 77.0% (n=800/1039) of patients with low systemic disease activity (ESSDAI<5). At the last follow-up, the mean ESSDAI was 2.1±3.7 (range 0-31), corresponding to a significant decrease from baseline (Figure 1A). Around 24% of patients experienced disease activity worsening, whereas 46% improved (Figure 1B).Finally, dryness, pain and fatigue PROs were high, and more importantly, had a significant increase from baseline to follow-up (Figure 1C). Conclusion: In the PORTRESS registry, a considerable number of patients do not have a full assessment of classification criteria, reflecting clinical practice. Systemic involvement was seen in most patients, although reduced salivary flow was present in only 1/5 of cases. Although systemic activity improved over follow-up, symptom burden worsened when compared to baseline, underlining a major unmet need in treating SjD. REFERENCES: NIL. Acknowledgements: This project was funded by SPCare; PORTRESS Reuma.pt Task Force: Sara P Dinis, Filipe Vinagre, Maria H Lourenço, Ana B Silva, Alexandra Daniel, Paula Valente, Inês Almeida, Joana Dinis, Lígia Silva, Lídia Teixeira, Filipe Araújo, Carlos M Gomes, Patrícia Pinto, Filipa Farinha, Teresa Nóvoa, Ana Rodrigues, Sara Cortes. Disclosure of Interests: Matilde Bandeira Research grant for this work: SPCare, Manuel Silvério-António Menarini; Theramex, Roberto Pereira da Costa: None declared, Ana Rita Lopes: None declared, Margarida Silva: None declared, Filipe Cunha Santos: None declared, Paulo Pereira: None declared, Diana B Raimundo: None declared, Anita Cunha: None declared, Cláudia Pinto Oliveira: None declared, Ana Catarina Duarte Boehringher Ingelheim, João Madruga Dias: None declared, Mariana Emília Santos: None declared, Maria João Gonçalves: None declared, Ana Catarina Moniz: None declared, Ana Maduro: None declared, Mariana Luis: None declared, Ana Valido: None declared, Margarida Oliveira: None declared, Luísa Brites: None declared, Catarina Tenazinha: None declared, Nikita Khmelinskii Paid instructor: GSKPaid speaker: Astrazeneca, GSK, Vifor PharmaPaid consultant: Abbvie, Astrazeneca, GSK, Novartis., Filipe Barcelos: None declared, Joao Eurico Fonseca: None declared, Vasco C Romão Speaking fees: Astrazeneca, Abbvie, GSK, Janssen, Lilly, Pfizer, SobiResearch Grants: MSD, SPCareTravel grants and scientific support: Abbvie, Lilly, Medac, MSD, Novartis, Pfizer, Roche.Figure 1Disease activity (A); ESSDAI variation between baseline and follow-up (B); Symptom burden (C) Table 1PORTRESS cohortPORTRESS cohort (n=1375)Age at diagnosis, y52.7±14.7Age at symptom onset, y47.9±14.8Diagnosis delay, y4.6±5.9Disease duration, y13.2±8.9Female1300 (95)AECG 2002747 (62)ACR/EULAR 2016758 (57)ANA1060 (91)Anti-Ro1061 (84)Anti-La541 (45)RF531 (48)Baseline ESSDAI3.0±4.4Baseline ESSPRI5.0±2.9USF <0.1ml/min161 (22)Schirmer’s ≤5mm/5min577 (59)Focus score1.6±2.1InvolvementConstitutionalLymphadenopathicGlandularArticularCutaneousPulmonaryRenalMuscularPNSCNSHematologicBiologicHepato/GastrointestinalOther228 (18)138 (11)387 (31)540 (43)223 (18)105 (8)34 (3)18 (2)49 (4)20 (2)429 (35)646 (52)36 (3)177 (16)TreatmentHydroxicloroquineCorticosteroidsPilocarpineMethotrexateAzathioprineRituximabLeflunomideMMFIVIGCyclophosphamide596 (65)265 (29)177 (19)110 (12)76 (8)29 (3)26 (3)19 (2)1 (0)1 (0)Results presented as mean±sd or n (%); USF – unstimulated saliva flow rate, PNS – peripheral nervous system, CNS – central nervous system; MMF – mycophenolate mofetil, IVIG – intravenous Immunoglobulin therapy

Background Disturbances in B cell immune responses have been implicated in rheumatoid arthritis (RA) pathogenesis since the first weeks of RA development. However, the mechanisms responsible for these immune alterations remain unclear. Follicular helper T (Tfh) cells are crucial for B cell maturation, activation and class-switching as well as for germinal center (GC) formation, whereas follicular regulatory T (Tfr) cells can modulate the GC reaction by suppressing Tfh and B cells. Objectives The main goal of this study was to analyze the frequency and phenotype of B, Tfh and Tfr cells in peripheral blood of untreated early RA patients when compared to patients with early non-RA polyarthritis, established RA and healthy controls. Methods Blood samples were collected from 35 untreated early polyarthritis patients (<1 year of disease duration), who later evolved into RA (early RA, ERA) (n=23) or other diagnoses (early non-RA, ENRA) (n=12); established seropositive RA patients (n=62) treated with methotrexate and a group of age- and sex-matched healthy controls (n=20). Peripheral blood mononuclear cells were isolated and the frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Results ERA patients had similar frequencies of B, Tfh and Tfr cells in circulation when compared to ENRA, established RA and controls. Nevertheless, ERA patients had significantly lower frequencies of pre-switch memory B cells (IgD+CD27+) and higher levels of double negative B cells (IgD-CD27-), CD21lowCD38low B cells and plasmablasts (IgD-CD38++) in peripheral blood when compared to controls. Furthermore, the frequencies of PD-1+ICOS+ Tfh cells and Th2-like Tfh cells were significantly increased in ERA patients when compared to controls. Changes in B, Tfh and Tfr cells phenotype were also observed in ERA patients when compared to controls, particularly an increase of the expression levels of activation markers (CD28, CD69, CD86 and HLA-DR). Conclusion ERA patients have alterations in B and Tfh cell subpopulations, but not in Tfr cells, in circulation when compared to healthy controls. Our results suggest a pre-activation state of B and Tfh cells since early RA development, which supports a role of these cells in disease physiopathology. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

AIMS:To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort.METHODS:Reuma.pt is a web-based system with standardised patient files gathered in a registry. This was a multicentre open cohort study, including patients registered in Reuma.pt/myositis up to January 2022.RESULTS:Reuma.pt/myositis was designed to record all relevant data in clinical practice and includes disease-specific diagnosis and classification criteria, clinical manifestations, immunological data, and disease activity scores. Two hundred eighty patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years. Patients were classified as having definite (N=57/118, 48.3%), likely (N=23/118, 19.5%), or possible (N=2/118, 1.7%) IIM by 2017 EULAR/ACR criteria. The most common disease subtypes were dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), and myositis in overlap syndromes (N=41/280, 14.6%). The most common symptoms were proximal muscle weakness (N=180/215, 83.7%) and arthralgia (N=127/249, 52.9%), and the most common clinical signs were Gottron's sign (N=75/184, 40.8%) and heliotrope rash (N=101/252, 40.1%). Organ involvement included lung (N=78/230, 33.9%) and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%). Cancer was found in 11/127 patients (8.7%), most commonly breast cancer (N=3/11, 27.3%). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), and mycophenolate mofetil (N=56/280, 20.0%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125).CONCLUSIONS:Reuma.pt/myositis adequately captures the main features of inflammatory myopathies' patients, depicting, in this first report, a heterogeneous population with frequent muscle, joint, skin, and lung involvements.

Background The idiopathic inflammatory myopathies (IMM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/Myositis) is a tool used to systematically evaluate IIM patients. Objectives To clinically characterise the Reuma.pt/Myositis cohort. Methods Multicentre open cohort study, including IIM patients registered in Reuma.pt up to January 2022. Data collected included demographic, clinical, and treatment data and patient-reported outcomes. Data were presented as frequencies and median (interquartile range) for categorical and continuous variables, respectively. Results 280 patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years, respectively. Patients were classified as having definite (N=57/118, 48.3%; N=35/224, 15.6%), likely (N=23/118, 19.5%; N=50/224, 22.3%), or possible (N=2/118, 1.7%; N=46/224, 20.5%) IIM by 2017 EULAR/ACR and Bohan-Peter criteria, respectively. Disease subtypes included dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), myositis in overlap syndromes (N=41/280, 14.6%), clinically amyopathic DM (N=17/280, 6.1%), nonspecific myositis (N=13/280, 4.6%), mixed connective tissue disease (N=12/280, 4.3%), immune-mediated necrotizing myositis (N=9/280, 3.2%), and inclusion bodies myopathy (N=7/280, 2.5%). Over the course of the disease, the most common symptoms were proximal muscle weakness (N=180/215, 83.7%), arthralgia (N=127/249, 52.9%), erythema (N=63/166, 38.0%), fatigue (N=47/127, 37.0%), Raynaud’s phenomenon (N=76/234, 32.5%), and dysphagia (N=33/121, 27.3%), and the most common clinical signs were Gottron’s sign (N=75/184, 40.8%), heliotrope rash (N=101/252, 40.1%), Gottron’s papules (N=93/237, 39.2%), and arthritis (N=38/98, 38.8%). Organ involvement included lung (N=78/230, 33.9%), oesophageal (N=40/221, 18.1%), and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) and/or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent antibodies were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%) at diagnosis, with median highest CK levels of 1308 (518-3172) and aldolase of 42 (12-121) mg/dL. Neoplasia was found in 11/127 patients (8.7%), most commonly breast (N=3/11, 27.3%), non-melanoma skin (N=2/11, 18.2%), and colorectal (N=2/11, 18.2%) cancer (Table 1). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs over the course of disease were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), mycophenolate mofetil (N=56/280, 20.0%), intravenous immunoglobulin (N=55/280, 19.6%), and rituximab (N=45/280, 16.1%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125). Table 1. Autoantibodies in cancer-associated myositis Cancer IIM Autoantibodies Breast DM (3) Mi2, SRP (+ SSA/SSB), Pm/Scl Skin (non-melanoma) Clinically amyopathic DM, PM Jo1, SAE1 (+SSA/SSB) Colorectal DM (2) Mi2 (2) Kidney DM - Lung DM - Lymphoma Inclusion bodies myopathy - Unknown DM - Conclusion Reuma.pt/Myositis adequately captures the main features of inflammatory myopathies’ patients, depicting in this first report a heterogeneous population, with frequent muscle, joint, skin and lung involvements. Of interest, most patients reached low disease activity at the last follow-up appointment. Disclosure of Interests None declared

Patients with inflammatory rheumatic diseases refractory to conventional disease modifying antirheumatic drugs (DMARDs)have been treated with biologics for the last two decades. It is also known that patients under biotechnological therapy present a higher risk of developing Tuberculosis (TB).Portugal has now a TB incidence classified as low. National recommendations advise on latent TB screening before the beginning of the biological therapy. This screening consists in the detection of risk factors and/or signs and symptoms of latent TB through clinical history, physical examination, chest X-ray, tuberculin skin test and Interferon Gamma Release Assay (IGRA) test. We describe five clinical cases of patients who underwent biotechnological therapy at our Hospital after 2006 and developed TB.

Background:Several studies have demonstrated that an immune dysregulation affecting both B and T cells occurs in rheumatoid arthritis (RA). Follicular helper T (Tfh) cells are crucial for B cell maturation, activation and class-switching as well as for germinal center (GC) formation, whereas follicular regulatory T (Tfr) cells can modulate the GC reaction by suppressing Tfh and B cells.Objectives:The main goal of this study was to analyze the phenotype and frequency of circulating follicular T cell subsets in established RA patients.Methods:Blood samples were collected from established RA patients with active disease, treated with methotrexate (n=32) and from a group of age and sex-matched healthy donors (n=11). Peripheral blood mononuclear cells (PBMC) were isolated and Tfh (CD4+CXCR5+CD45RO+) and Tfr (CD4+ CXCR5+CD25+FoxP3+) cells, as well as their three major subsets [CXCR3+CCR6- (Th1-like), CXCR3-CCR6- (Th2-like) and CXCR3-CCR6+ (Th17-like)] were evaluated by flow cytometry.Results:The frequency of circulating Tfh cells was similar between established RA patients and controls. Nonetheless, RA patients had a decreased frequency of Th1-like Tfh cells, and an increased frequency of Th2-like Tfh cells when compared to controls. No significant differences were observed in the frequencies of Th17-like Tfh cells between both groups. The frequency of circulating Tfr cells was significantly increased in RA patients in comparison to controls. Furthermore, Tfr cells from RA patients had significantly increased CD69 median fluorescence intensity (MFI) values when compared to controls. No significant differences were found in the percentages and MFI values of PD-1, ICOS, CD28, CTLA-4, CD40-L and HLA-DR expressed by Tfh and Tfr cells in RA patients when compared to controls.Conclusion:Established RA patients have increased circulating frequencies of Tfr cells, with higher CD69 expression levels, when compared to healthy controls. These results suggest a pre-activation state of Tfr cells in RA and a potential role in the disease physiopathology.*RA Moura, JE Fonseca and L Graca are joint senior authors.Disclosure of Interests:None declared

Background: Hepatitis B virus (HBV) vaccination is recommended for rheumatic patients starting biologic therapy. There is some evidence that HBV vaccination is effective in patients under conventional disease modifying anti-rheumatic drugs (DMARDs), but it is currently unclear whether this also applies to biologics. Objectives: To assess the efficacy and safety of HBV vaccination in patients with rheumatic diseases treated with biologics. Methods: We included patients with any inflammatory rheumatic diseases treated with any biologic, who were negative for anti-HBs and anti-HBc and had never been vaccinated for HBV. Engerix B® was administered at 0, 1 and 6 months and anti-HBs was re-assessed ≥1 month after last dose. Response was defined as anti-HBs>10IU/L and compared against healthy controls (HC) undergoing Occupational Health immunization. Disease flare was evaluated before and until at least 1 month post-vaccination. We recorded serious adverse events (SAE) and immune-related disorders not previously present. Results: We included 67 patients, most treated with TNF inhibitors (TNFi), and 70 HC (Table 1). Most patients were taking concomitant DMARDs (69%) and were in remission/low disease activity (59%). Only 20 patients (30%) had a positive response to vaccination, in comparison to 68 HC (97%, p<0.001). Mean post-vaccination anti-HBs titre was significantly lower in responding patients than HC (569 ± 772 vs 1316 ± 811U/L, p<0.001). Responders diagnoses were RA (n=8 [25%]), PsA (n=7 [39%]), AS (n=4 [33%]) and IBD-associated SpA (n=1[100%]). Response was seen in 19/53 patients treated with TNFi (36%), but only 1/14 (7%) of patients treated with non-TNFi (p=0.037). Importantly, some responders had to temporarily interrupt biologic therapy due to other intercurrences for at least one administration. No clinical or demographic variables were associated with response, including age and disease activity. Fourteen patients (21%) experienced disease flares, of which 7 were mild and did not require therapy adjustment; 3 patients required minor treatment/dose adjustments; 4 patients had secondary failures that led to switches. There were 3 SAE (acute diverticulitis; abdominal infection; atrial fibrillation and urinary infection) 1-4 months after 1 st /2 nd dose, deemed not to be related to vaccination. One RA patient on infliximab had bilateral uveitis 2 months after the 1 st vaccine dose, which resolved with topical therapy. Table 1. Baseline characteristics of study participants. Patients (n=67) Controls (n=70) p Age (years) 56 ± 9 46 ± 9 <0.001 Female (%) 40 (60) 62 (89) <0.001 Diagnosis (%) RA 32 (48) PsA / AS 18 (27) / 13 (19) Other 4 (6) Disease duration (years) 17 ± 10 Biologic (%) TNF-inhibitor 53 (79) Tocilizumab / Abatacept 6 (9) / 1 (1) Rituximab / Belimumab 2 (3) / 4 (6) Anakinra 1 (1) Conventional DMARDs (%) MTX / LEF 39 (58) / 1 (1) SSZ / Other 6 (9) / 3 (4) None 21 (31) Prednisolone (%) / Dose (mg) 29 (43) / 5.6 ± 2.1 DAS28 3.1 ± 1.4 ASDAS 2.2 ± 1.4 Conclusion: In this study, HBV vaccination response was poor and lower in rheumatic patients treated with biologic therapy than in healthy adults. Vaccination was overall safe but there were 4 severe flares and 3 SAE that lead to treatment switch/interruption, although causal association is difficult to establish. Our data reinforce the recommendation for HBV vaccination prior to starting biologic therapy, possibly even as soon as the diagnosis is established. Alternative HBV vaccination strategies should be investigated in patients already treated with biologics. Disclosure of Interests: Vasco C Romão: None declared, Pedro Ávila-Ribeiro Grant/research support from: Novartis, Maria João Gonçalves: None declared, Ana Rita Cruz-Machado: None declared, André Guerreiro: None declared, Vítor Teixeira: None declared, Ana Valido: None declared, Joana Silva-Dinis: None declared, Elsa Vieira-Sousa: None declared, Maria João Saavedra: None declared, Ema Leite: None declared, Rui Tato Marinho: None declared, Joao Eurico Fonseca: None declared

Background: The information associated with loss to follow-up (LFU) patients may affect real-world data evaluation of the use of biologics that is not being adequately captured in registries. Methods: We identified all patients (Pts) treated with biologics in our center who had no visits registered for more than 6 months, in the Rheumatic Diseases Portuguese Register, Reuma.pt. We retrieved baseline information from Reuma.pt and from the hospital electronic clinical record. We then performed a telephonic interview to characterize the reasons for LFU at our day care unit. For Pts unable to be contacted by telephone a letter of invitation to an appointment at the hospital was sent. Results: From a total of 794 Pts registered in Reuma.pt at our center with active biologic therapy 227 did not have any information registered in the last 6 months. Of this, 36 Pts were on biologic therapy prescribed by other departments and maintained follow-up in these departments. 102 Pts had suspended biologic administration by medical indication and this information was registered in the hospital electronic clinical records but not updated in Reuma.pt. For 89 Pts no information could be retrieved from either the hospital electronic clinical record or Reuma.pt and we classified these Pts as true LFU. 26 of these LFU Pts were being followed up in another Rheumatology center. 26 of the LFU Pts died. 11 Pts had an adverse effect. 4 Pts of the LFU were considering to be in remission. We were not able to contact 15 of the LFU pts. Conclusion: Identifying LFU Pts and clarifying the reason for the loss of data in a register contributes to a better knowledge on strategies to discontinue biologics in stable pts, to a better pharmacovigilance of adverse effects and to more efficiency in data capture by registries. Due to data protection reasons it was impossible to have access to the Pts's death certificates.

OBJECTIVES To compare the effectiveness of a 2nd TNF inhibitor (TNFi), Tocilizumab (TCZ) and Rituximab (RTX), measured by drug retention and by response rates, in RA patients after discontinuing a first-line TNFi and to clarify the reasons and predictors for discontinuation of a second-line biologic. MATERIAL AND METHODS Non-interventional prospective study of RA patients exposed to a 2nd TNFi, TCZ or RTX after previous TNFi discontinuation using real-world data from Reuma.pt database. Drug retention was estimated using Kaplan-Meier analysis and Cox models. Crude and LUNDEX adjusted response rates were evaluated at 6 months, 1 and 2 years and reasons for discontinuation were compared according to biologic class. RESULTS In total, 643 patients were included, 88.8% females, with a mean age of 59.4±12.8 years. Of those, 390 (60.7%) initiated a 2nd TNFi, 147 (22.9%) TCZ and 106 (16.5%) RTX. Drug retention was significantly greater among patients who initiated TCZ (76.4±4.3 months) or RTX (80.8±4.8 months), compared with those who initiated a 2nd TNFi (52.7±2.6 months) (log rank test, p < 0.001). In the adjusted Cox model, hazards of discontinuation were significantly lower for TCZ (HR 0.39, 95% CI 0.23-0.64, p < 0.001) and RTX (HR 0.42, 95% CI 0.25-0.72, p=0.001). Smokers had a significantly higher risk for discontinuation (HR 2.43, 95%CI 1.50-3.95, p < 0.001) as well as patients with higher HAQ at baseline (HR 1.51, 95%CI 1.14-2.00, p=0.004). The proportion of patients in remission or low disease activity according to Clinical Disease Activity Index (CDAI) at 6 months, 1 and 2 years was, respectively, 46.5%/50.0%/61.2% for TNFi, 52.9%/53.6%/ 69.2% for TCZ and 37.7%/48.0%/50.0% for RTX. After LUNDEX adjustment, response rates were, respectively, 33.0%/31.0%/31.8% for 2nd TNFi, 42.8%/41.8%/53.3% for TCZ and 32.0%/39.4%/39.0% for RTX. The main reasons for discontinuation were inefficacy for 2nd TNFi and RTX and adverse events for TCZ (p < 0.001). CONCLUSIONS Our findings showed a significantly higher drug retention for TCZ and RTX, compared with 2nd TNFi, and similar persistence among TCZ and RTX, in patients who discontinued a first-line TNFi. These data corroborate the notion that switching to a biologic with a different mode of action is more effective than to a second TNFi.

Background Portugal has made an official commitment for improving health in Portuguese speaking African countries (PALOP) by allowing an annual quota of patients evacuated from these countries for medical reasons. The agreements pretend to compensate difficulties in health care access and medical resources of these populations. However, the bureaucratic process that mediates the displacement of patients to Portugal is invariably complex and delayed, so these aims are commonly not achieved. Objectives to report our experience dealing with PALOP rheumatic patients and evaluate their outcomes. Methods a retrospective analysis of patients evacuated from PALOP and referred due to rheumatic diseases or potentially related conditions, followed-up in our Department for the last 7 years. Clinical data was collected until September 2017. Results a total of 58 patients (77.6% female), with an average age of 33.5 years (±SD 15.2; range 2–78 years) were included, representing Guinea-Bissau 44.8%, Cape Verde 27.6%, São Tomé and Príncipe 17.2% and Angola 10.3%. Of all these patients, only 44.8% were primarily referred to our Department. The majority (55.2%) had no previous diagnosis, 19% were considered to have a wrong diagnosis and 25.9% were well diagnosed. After assessment in our Department, we ended up with the diagnoses listed, mainly SLE (17.2%) and Rheumatoid Arthritis (17.2%). The mean duration of symptoms was 62.4 months (minimum 1 month; maximum 40 years). From the evacuation request until effective journey patients waited a mean of 13.9 months (missing data in 37 patients). At arrival, only 25.9% of patients were or had been on corticosteroids and only 15.5% on conventional disease modifying antirheumatic drug (DMARD) treatment, versus 62% and 67.2%, respectively, after assessment in Portugal (graphic). Even common and cheap drugs, like prednisolone and hydroxychloroquine were underprescribed before our assessment. Twelve percent of patients required biologics. Hospitalizations related to disease activity or complications were required in 43.1%. Severe damage, measured by indication for orthopaedic, cardiothoracic or vascular surgery, need of chronic dialysis or long-term oxygen therapy and permanent neurologic deficits was present in 34.5% of the patients. Three patients died. Regarding infectious comorbidities, 12.1% of patients were diagnosed with tuberculosis, 8.6% had chronic hepatitis B infection and 12.1% had evidence of previous contact with hepatitis B virus. Conclusions PALOP patients present with long-lasting and severe rheumatic diseases with chronic damage, due to lack of precise diagnosis, ineffective referrals and lack of appropriate treatment. They also frequently present with important infectious comorbidities and social needs that may delay treatment. Despite the obvious advantages of the evacuation of patients to a more resourceful country, we believe there is a need for identification of onsite barriers and improvement of local awareness on Rheumatic diseases and Rheumatology speciality. Disclosure of Interest None declared

Objectives The aim of this study was to analyse efficacy, safety and cost savings of switching from infliximab originator (IFXor) to the biosimilar (BS) CT-P13 in single centre. Methods Eligible patients were those older than 18 years old with the diagnosis of rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) on treatment (Tx) with IFXor for at least 6 months and with stable disease activity. In December 2016 all eligible patients were proposed to switch to CT-P13. At the day of the last Tx with IFXor, informed consent, data and blood samples were collected. On the next Tx day, CT-P13 was administered after standard evaluation of efficacy and safety. Efficacy was measured considering change from baseline in Disease Activity Score in 28 joints (DAS28) for RA and PsA and in Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Disease worsening was considered when an increase of 1.2 from baseline in DAS28 or an increase of 1.1 in ASDAS occurred. A cost analysis was done based on the purchasing prices of the 2 drugs at our centre. Results In a 12 months period switch to CT-P13 was performed in 60 patients for non-medical reasons. Disease activity (DA) was stable over the observation period and similar to the values observed with IFXor. Median follow-up time was 261 days during which disease worsening occurred in 3 (5%) patients. 1 patient had a minor adverse event (oedema of the lip). These 4 (6.7%) patients stopped the BS. One returned to IFXor and the other 3 switched to another drug. The switch to CT-P13 represented a 26.4% reduction of costs in the use of IFX Tx in these patients.Abstract AB1231 – Table 1 Numbers are medians unless otherwise stated. Total (n=60) SpA (n=36; 60%) RA (n=16; 27%) PA (n=8; 13%) Age (years) 53 (48–64) 50 (41–59) 59 (52–70) 56 (48–64) Gender (n,% male) 39 (65%) 30 (83%) 2 (13%) 7 (88%) Disease duration (years) 17 (10–23) 16 (10–22) 18 (13–24) 16 (10–22) Patients on methotrexate 41 (68%) 20 (33%) 15 (25%) 6 (10%) Patients with previous biologic therapy 4 (6.7%) 1 (2.8%) 3 (18.8%) 0 (0%) Time on IFX originator before switch (years) 7.9 (6.5–11.9) 7.7 (6.4–12.3) 8.4 (6.7–12.4) 7.6 (6.7–9.6) Time on CT-P13 since switch (months) 9 (7–11) 9 (7–11) 10 (9–10) 9 (4–10Abstract AB1231 – Table 2 Variables median from baseline to 9 months after switch to CT-P13. ESR – Erythrocyte Sedimentation Rate; CRP – C-Reactive Protein; PtGA – Patient global assessment of DA; PhGA – Physician global assessment of DA. Baseline 3 Months after switch 6 Months after switch 9 Months after switch Variation from baseline to 9 Months after switch ESR (mm/h) 15 (10–21) 17 (9–29) 15 (9–24) 15 (9–24) 0 CRP (mg/dL) 0.18 (0.80–0.57) 0.17 (0.06–0.50) 0.19 (0.10–0.46) 0.25 (0.10–0.72) 0.07 PtGA (0–100) 30 (20–50) 20 (30–50) 30 (3–50) 30 (15–50) 0 PhGA (0–100) 20 (10–30) 20 (10–30) 20 (0–30) 20 (10–30) 0Abstract AB1231 – Figure 1 Conclusions The switch in routine care of a group of RA, SpA and PsA patients from IFXor to CT-P13 did not affect efficacy and safety and reduced costs in 26.4%. Reference [1 ] Bente Glintborg, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis 2017;0:1–6. Disclosure of Interest None declared

Background: Norway9s government funded the NOR-SWITCH study to investigate switching from originator infliximab (INX) to biosimilar CT-P13 in Crohn’s disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and chronic plaque psoriasis (Ps). Previously, the main analyses have been published1. Immunogenicity is associated with treatment failure and is of particular concern in switching2. Objectives: To evaluate the consistency and fine specificity of anti-drug antibody (ADAb) responses to INX and CT-P13, in arthritis and IBD patients, after switching from INX to CT-P13. Methods: The study included adult patients with CD, UC, SpA, RA, PsA or Ps1. Assays for drug serum levels and ADAb have been described1. ADAb positive sera were tested for cross-reactivity to 5 batches of INX and CT-P13. We quantified IgG4 ADAb, testing for functional inhibition. Infliximab peptides were used to compare epitope recognition of positive sera. Immunogenic infliximab-epitopes were identified by ELISA and sera compared across diseases. Results: We tested 15 controls, 15 arthritis, 21 IBD patients. No Ps patients had ADAbs in our study. All 23 anti-CT-P13 and 13 anti-INX sera cross-reacted with INX and CT-P13, respectively. ADAb concentrations to INX or CT-P13 correlated strongly (r values between 0.92 and 0.99, p<0.001 for all experiments, Spearman’s correlation test). Sera negative for CT-P13 ADAb (10 healthy controls, 5 RA patients) were also anti-INX negative. IgG4 ADAb in all sera recognized 5 different batches of CT-P13 and INX. All positive sera had similar functional inhibition of CT-P13 or INX TNF-binding capacity, showing reduced binding to CT-P13 in the presence of 5 different batches of CT-P13 and INX. 60%_79% of patients recognized 7 synthetic peptides corresponding to major anti-infliximab epitopes, with no significant differences between CT-P13 and INX ADAb. Three minor epitopes in framework regions of infliximab showed reduced antibody reactivity in 30%_50% of patients. Stratifying by diagnostis, we found two epitopes in the variable and constant heavy-chains of infliximab specifically recognized in IBD patients but not rheumatic patients. Conclusions: ADAbs to INX also recognize CT-P13, with similar epitopes. We found no consistent difference in ADAb epitope specificity between diagnoses. However, two specific minor epitopes are only recognized by IBD patients which might reflect the importance of HLA background for ADAb. References 1. Jørgensen KK, Olsen IC, Goll GL, et al. Switching from originator infliximab to biosimilar CT-P13 compared to maintained treatment with originator infliximab (NOR-SWITCH): a 52-week randomised double-blind non-inferiority trial. Lancet, 2017Jun 10;389(10086):2304–2316. [Epub 2017 May11]. 2. Dörner T, Jay J. Biosimilars in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol2015Dec;11(12):713–24. Disclosure of Interest: G. Goll Consultant for: AbbVie, Biogen, Eli Lilly, Novartis, Pfizer, MSD, Roche, UCB, Boehringer Ingelheim, Orion Pharma, N. Bolstad Consultant for: Pfizer, Orion Pharma, Napp Pharmaceuticals, I. Iria: None declared, R. Klaasen: None declared, K. Jorgensen Consultant for: Tillott, Celltrion, Intercept, I. Olsen Consultant for: Pfizer, A. Valido: None declared, M. Saavedra: None declared, J. Fonseca Consultant for: AbbVie, Ache, Amgen, Biogen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, K. Lundin Grant/research support from: MSD, Consultant for: Takeda, Orion, AbbVie, Rfizer, MSD, D. Warren: None declared, E. Haavardsholm Consultant for: AbbVie, Pfizer, MSD, Roche, UCB, J. Jahnsen Consultant for: AbbVie, Takeda, Janssen, Celltrion, Napp, AstroPharma, Hikma, Orion, Pfizer, T. Kvien Consultant for: AbbVie, Biogen, Eli Lilly, Novartis, Pfizer, MSD, Roche, UCB, Boehringer Ingelheim, Orion Pharma, J. Goncalves Consultant for: AbbVie, Amgen, Biogen, MSD, Pfizer