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Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response.

Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<105/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61–18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease typically associated with psoriasis and classified in the group of spondyloarthritis (1). The pathogenesis is based on an interplay of different genes interacting with several environmental factors including stress, trauma, infections, triggering an inflammatory response related to the activation of innate and acquired immunity in different tissues and organs (2). However, the risk for the development of PsA is not clearly understood. The aim of this study was to evaluate, in a cohort of Italian PsA out-patients of the Rheumatology Unit of the University of Rome Tor Vergata, the association of genetic variants in candidate genes for PSA susceptibility and their possible contribute in the modulation of clinical and laboratory features. The genes were selected according to previous studies describing these genes as involved in susceptibility to rheumatoid arthritis (RA) (3), since a common genetic background can be shared between these diseases. Nine SNPs (single nucleotide polymorphism) in eight candidate genes were analysed: STAT4 (rs7574865), TRAF3IP2 (rs33980500), TNFAIP3 (rs6920220 and rs2230926), MIR146A (rs2910164), PSORS1C1 (rs2233945), IL-10 (rs1800872), HCP5 (rs3099844) and ERAP1 (rs27524). Polymorphisms were analysed in 163 consecutive PsA out-patients and 198 healthy controls (HC). Genotyping was performed by allelic discrimination by TaqMan assay. Alleles frequencies differences between cases and controls or between phenotypic groups were compared using Pearson's χ 2 test. We have observed an association between PSA susceptibility and the variant alleles of STAT4 [OR= 1.60 (1.15-2.21), P= 0.005], TRAF3IP2 [OR= 1.65 (1.01-2.65), P= 0.04], ERAP1 [OR= 1.40 (1.05-1.85), P= 0.02] and TNFAIP3 (rs6920220) [OR= 1.75 (1.19-2.57), P= 0.004]. On the contrary, the variant allele of IL-10 polymorphism seems to play a protective role [OR= 0.74 (1.05-1.85), P= 0.05]. Moreover, in order to define a genetic risk profile, we have counted the total number of risk alleles in each subject, considering as risk alleles the allelic variant of rs7574865 (STAT4), rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3) and rs27524 (ERAP1) SNPs. Then, we have compared the risk allele number distribution between patients and HC (Fig.1). Classes with 3 or more risk alleles are significantly more represented in patients than in HC (OR= 2.03, P=0.004). The risk to develop the disease increases significantly in subjects with at least four risk alleles (OR= 2.96, P=0.002). We confirm the associations between five SNPs, already studied in RA, and PSA susceptibility, suggesting a common inflammatory pathway in chronic inflammatory rheumatological diseases. Moreover, we show how the genotyping of only few associated SNPs could help to define a genetic risk profile for PSA development. [1]Calabresi E, et al. One year in review 2019: psoriatic arthritis. Clin Exp Rheumatol. 2020;38:1046-55. [2]Chimenti MS, Triggianese P, De Martino E, Conigliaro P, Fonti GL, Sunzini F, Caso F, Perricone C, Costa L, Perricone R. An update on pathogenesis of psoriatic arthritis and potential therapeutic targets. Expert Rev Clin Immunol. 2019 Aug;15(8):823-836. [3]Ciccacci C, et al. Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis. Clin Exp Immunol. 2016;186:157-63. None declared [Display omitted]

Background:Enteropathic Spondyloarthritis (ESpA) belongs to the group of Spondyloarthritis (SpA) typically associated with inflammatory bowel disease (IBD). SpA are divided into axial (ax) or peripheral disease. Ax-SpA are classified as ankylosing spondylitis (AS) and non-radiographic (nr-) axSpA based on the presence or absence of definite structural changes in conventional radiographs (CR).Objectives:Aim of this study was to determine whether comorbidities and gender could lead to a different response rate to TNF-inhibitors (TNFi) in ESpA patients.Methods:ESpA patients treated with TNFi [adalimumab (ADA) or infliximab (IFX)] were retrospectively evaluated between November 2018 and October 2020 and divided in two cohort according to gender. In addition, TNFi treatments line/s, effectiveness and reasons of discontinuations, as inefficacy, intolerance, acute adverse reaction, development of infections and other causes, were evaluated at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months of therapy. Patients who were failure to at least two TNFi were considered as “multifailure”. Statistical analyses were performed using chi square/Fisher tests and variance analysis (SPSS software).Results:120 ESpA patients (M 40.52%; F 40.18%) treated with TNFi were evaluated. Clinical and laboratory baseline (T0) characteristics are summarized in Table 1. AS subtype was more common in men (39.5%) than in woman (14.3%) (p=0.03). Concerning comorbidities, hypertension and anemia were more prevalent in men than women (25% vs 9%, p=0.01; 11.6% vs 1.3%, p=0.02, respectively), while thyreopathy and psychiatric disorders were more common in female than male (11.7% vs 0%, p=0.02; 16.9% vs 4.6%, p=0.04, respectively). No difference was observed between genders in distribution of BMI, smokers, disease duration, HLAB27 positivity and presence of extra-articular manifestations. 202 TNFi treatments (50.9% ADA and 24.3% IFX) were evaluated in 120 patients [74 treatments (36.6%) in 43 men; 128 treatments (63.4%) in 77 women]. Considering treatment effectiveness, higher prevalence of failure was observed in woman that in men (67.2% vs 39.2%, p=0.0005). Moreover, women with psychiatric disorders undergone more lines treatment that men (16.8% vs 4.6%, p=0.01, OR=4). On the other hand, men with hypertension, were more multifailure compared with women (25.6% vs 16.3%, p=0.001, OR=3). No other differences according to gender were found.At T6, 7.5% of patients (n=9) had acute adverse reaction (n=1 with ADA; n=8 with IFX); at T12, 14.2% of patients (n=17) had IBD inefficacy. At T24, secondary inefficacy on IBD and/or SpA was the main cause of TNFi discontinuation compared with other causes (58.4% vs 41.6%; p=0.04), mostly in female cohort (40% vs 20% in woman; p=0.04). Analyzing TNFi effectiveness, CRP and HAQ improvement was noted at T6 (p=0.024 and 0.036, respectively), as ASDAS-CRP and BASDAI (p=0.02 and p=0.013, respectively) and maintained in the following evaluations at T12 and T24. At T24, men shown higher PCR and BASDAI improvement compared with women (p=0.036 and p=0.04, respectively).Conclusion:Data suggest that gender and comorbidities could influenced TNFi response in ESpA patients, advising differences among woman and men. Knowledge of these variable represents a major challenge for a personalized treatment management.Disclosure of Interests:None declared.

Micronutrient deficiencies (MNDs) are common among patients with chronic inflammatory diseases. These are associated with a pro-inflammatory status and co-morbidities, and influenced by several factors, such as age and gender. No any study has investigated MNDs and their correlation with gender in Spondyloarthritis (SpA). With this purpose, this study analyzed the occurrence of anemia and the status of ferritin (Fe), vitamin D [25(OH)D], vitamin B12 (B12), and folic acid (FA) in a cohort of patients with SpA. Levels of Hb, Fe, 25(OH)D, B12, FA, were evaluated in 220 SpA outpatients (137 females and 83 age-matched males) with Psoriatic arthritis (PsA, n=110) and SpA (n=110). Disease activity was assessed by DAPSA or ASDAS-CRP as appropriate and functional status was evaluated with HAQ score. Body Mass Index (BMI) was selected as a metabolic clinic parameter. Male and female patients were similar for disease duration and severity as well as the distribution of diagnosis and treatments (Table 1). In males, BMI was higher than in females (P=0.03) and positively correlated with the age (P=0.01). In female patients, BMI directly correlated with HAQ (P=0.03). The prevalence of anemia (Hb<12) was 13.6% of the study cohort; half of anemic patients had PsA, the others had enteropathic SpA (ESpA). Anemia resulted almost wholly in female patients (99%). In the male group, Hb resulted inversely related to age (P=0.01) and CRP levels (P=0.008). Ferritin was lower in females than in males (P=0.0003). 25(OH)D deficiency (≤20 ng/ml) was present in 23.2% of the cohort: males had lower 25(OH)D than females (P=0.02). Among male patients, disease duration correlated positively with ferritin (P<0.001) and inversely with 25(OH)D (P=0.02). Low levels of serum B12 (≤200 pmol/l) were rare (13.2%), while deficiency in FA (≤4 ng/ml) was frequent (22%) and associated with B12 defect in 31% of cases, with almost similar occurrence in males and females. A diagnosis of ESpA occurred in 55% of cases with B12 deficiency and 62.5% of FA defect, without gender difference. Mean levels of ferritin, 25(OH)D, B12, and FA did not differ significantly between PsA and SpA patients. Our study describes for the first time the possibility of a relevant prevalence of MNDs in SpA patients. Furthermore, we show that MNDs could be also influenced by gender difference and age. Of note, our findings highlight the importance of a screening focused on MNDs in SpA patients. This could be key in optimizing management of SpA patients, in which inflammatory-dependent dysmetabolism is frequent. [1]Yamamoto EA, Jørgensen TN. Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity. Front Immunol. 2020;10:3141. [2]Charoenngam N, Holick MF. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients. 2020;12:2097. [3]Bañuls-Mirete M, Ogdie A, Guma M. Micronutrients: Essential Treatment for Inflammatory Arthritis? Curr Rheumatol Rep. 2020;22:87. None declared. Table 1Data from the study population.Females (n=137)Males (n=83)PAge (yrs; §)51.65 ± 1352.9 ± 12.8NSBMI (*)24 [17.2 - 50.2]25.8 [19.6 - 43.6]< 0.05CRP (mg/l; *)2.9 [0 - 53]2 [0 - 61]NSHb (g/dl; §)13 ± 1.214.4 ± 1.4NSFe (mg/l; *)37 [2 - 148]64 [4 - 452]< 0.0525(OH)D (ng/ml; *)28.2 [5 - 67]25 [5 - 50]< 0.05Vitamin B12 (pmol/l; *)350 [60 - 990]313 [47 - 797]NSFolic Acid (ng/ml; *)7 [1.7 - 40]6.9 [1.8 - 39]NSPsA (N/%)73/68.2334/31.77NSSpA (N/%)64/4149/59NSConcomitant IBD (n/%)56/65.929/34.1NSDisease duration (months; *)69 [6 - 540]76.5 [3 - 768]NSLow D.A. (N/%)62/45.2547/56.6NSModerate-high D.A. (N/%)75/54.7536/43.4NSCOXIB-inhibitors (N/%)21/15.48/9.6NScDMARDs monotherapy (N/%)35/25.510/12NSbDMARDs (N/%)81/59.1265/78.4NSBMI, body mass index; CRP, C-reactive protein; Hb, haemoglobin; Fe, ferritin; 25(OH)D, vitamin D; PsA, psoriatic arthritis; SpA, spondyloarthritis; IBD, inflammatory bowel disease; D.A., disease activity; cDMARDs, conventional Disease Modifying Antirheumatic Drugs; bDMARDs, biological DMARDs; § mean ± SD; * median [min-max].

Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders.

Objective. To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. Methods. We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. Results. The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). Conclusions. Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Background:There are still unmet needs in the treatment of psoriatic arthritis (PsA), including in terms of treatment persistence, which is a function of effectiveness, safety and patient satisfaction. Ustekinumab (UST) was the first new biologic drug to be developed for the treatment of PsA after tumour necrosis factor inhibitors (TNFi).Objectives:To compare treatment persistence, effectiveness and safety of UST and TNFi in Italian patients within the PsABio cohort.Methods:PsABio (NCT02627768) is an observational study of 1st/2nd/3rd-line UST or TNFi treatment in PsA in 8 European countries. The current analysis set includes 222 eligible patients treated in 15 Italian centres, followed to Month 12 (±3 months). Treatment persistence/risk of stopping was analysed using Kaplan−Meier (KM) and Cox regression analysis. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity Index for PsA (cDAPSA) low disease activity (LDA)/remission were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation of effectiveness endpoints if treatment was stopped/switched before 1 year. Last observation carried forward data are reported.Results:Of patients starting UST and TNFi, 75/101 (74.3%) and 77/121 (63.6%), respectively, persisted with treatment at 1 year. The observed mean persistence was 410 days for UST and 363 days for TNFi. KM curves and PS-adjusted hazard ratios confirmed significantly higher persistence (hazard ratio [95% confidence interval (CI)]) for UST versus TNFi overall (0.46 [0.26; 0.82]; Figure 1). Persistence was also higher for UST than TNFi in patients receiving monotherapy without methotrexate (0.31 [0.15; 0.63]), in females (0.41 [0.20; 0.83]), and in patients with body mass index (BMI) <25 kg/m2 (0.34 [0.14; 0.87]) or >30 kg/m2 (0.19 [0.06; 0.54]). There was no significant difference in persistence between treatments in patients with BMI 25−30 kg/m2. While patients receiving 1st- and 3rd-line UST or TNFi showed similar risk of discontinuation (0.60 [0.27; 1.29] and 0.36 [0.10; 1.25], respectively), patients receiving 2nd-line UST showed better persistence than those receiving 2nd-line TNFi (0.33 [0.13; 0.87]). Other factors added to the PS-adjusted Cox model did not show significant effects. In patients with available follow-up data, the mean (standard deviation) baseline cDAPSA was 26.3 (15.4) for UST and 23.5 (12.3) for TNFi; at 1-year follow-up, 43.5% of UST- and 43.6% of TNFi-treated patients reached cDAPSA LDA/remission. MDA was reached in 24.2% of UST- and 28.0% of TNFi-treated patients, and VLDA in 12.5% of UST- and 10.2% of TNFi-treated patients. After PS adjustment (stoppers/switchers as non-responders), odds ratios (95% CI) at 1 year did not differ significantly between UST and TNFi groups for reaching cDAPSA LDA/remission (1.08 [0.54; 2.15]), MDA (0.96 [0.45; 2.05]) or VLDA (0.98 [0.35; 2.76]). In total, 23 (20.4%) patients reported ≥1 treatment emergent adverse event with UST and 30 (22.2%) with TNFi; 6 (5.3%) and 10 (7.4%) patients, respectively, discontinued treatment because of an adverse event.Conclusion:In the Italian PsABio cohort, UST had better overall persistence compared with TNFi, as well as in specific subgroups: females, patients on monotherapy without methotrexate, with BMI <25 or >30 kg/m2, and patients receiving UST as 2nd-line treatment. At 1 year, both treatments showed similar effectiveness, as measured by cDAPSA responses and MDA/VLDA achievement.Acknowledgements:This study was funded by Janssen. Contributing author: Prof. Piercarlo Sarzi-Puttini, ASST Fatebenefratelli-Sacco, University of Milan, ItalyDisclosure of Interests:Elisa Gremese: None declared, Francesco Ciccia Speakers bureau: AbbVie, Abiogen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: Celgene, Janssen, Novartis, Pfizer, Roche, Carlo Selmi Speakers bureau: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Consultant of: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, Giovanna CUOMO: None declared, Rosario Foti Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Marco Matucci Cerinic Speakers bureau: Actelion, Biogen, Janssen, Lilly, Consultant of: Chemomab, Grant/research support from: MSD, Fabrizio Conti Consultant of: AbbVie, Bristol-Myers Squibb, Galapagos, Lilly, Pfizer, Enrico Fusaro Speakers bureau: AbbVie, Amgen, Lilly, Grant/research support from: AbbVie, Pfizer, Giuliana Guggino Speakers bureau: AbbVie, Celgene, Novartis, Pfizer, Sandoz, Grant/research support from: Celgene, Pfizer, Florenzo Iannone Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Andrea Delle Sedie: None declared, Roberto Perricone: None declared, Luca Idolazzi Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Sandoz, Paolo Moscato: None declared, Elke Theander Employee of: Janssen, Wim Noel Employee of: Janssen, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Silvia Marelli Employee of: Janssen, Laure Gossec Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Grant/research support from: AbbVie, AstraZeneca, Lilly, Novartis, Roche.

Golimumab showed trial efficacy in subjects with active rheumatoid arthritis (RA) previously treated with TNF-inhibitors (TNFi); no trial data are available for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). To assess the effectiveness of golimumab after TNFi failure in patients with RA, PsA, or axSpA in a real-world setting. GO-BEYOND-Italy is an ongoing, multicenter, prospective, observational study of RA, PsA, or axSpA patients starting golimumab after TNFi failure. Patients were enrolled between July 2017 and December 2019, and followed for 1 year, with evaluations at 3, 6, and 12 months. This interim analysis estimates the effectiveness after 3 months of golimumab therapy. Differences from baseline were tested by paired t-tests. 193 patients were enrolled: 38 (19.7%) with RA (median age 54 years; median disease duration 9.5 years), 91 (47.2%) with PsA (median age 53 years; median disease duration 9.0 years) and 64 (33.2%) with axSpA (median age 54 years; median disease duration 7.2 years). Majority of the RA (73.7%), PsA (51.6%) and axSpA (53.1%) were females. Previous TNFi treatment included etanercept (44.6% of patients), adalimumab (42.0%), infliximab (8.8%) and certolizumab (4.7%). The main reason for switching to golimumab was loss of efficacy of TNFi (78.9% in RA, 83.5% in PsA, 75% in axSpA). Comorbidities were highly prevalent (RA 65.8%, PsA 65.9%, axSpA 75%); hypertension (31.1%), dyslipidaemia (13.5%), fibromyalgia (10.4%) were the most common ones. DAS28-CRP significantly reduced in RA and PsA (p<0.01) after 3 months of treatment. In RA, rates of DAS28-CRP remission and low disease activity (LDA) were 29.6% and 22.2%, respectively, and 65.2% of patients achieved good/moderate EULAR response. As for PsA, good/moderate EULAR response was observed in 78.8% of patients and 28% of patients achieved minimal disease activity. In axSpA, ASDAS-CRP (p<0.01), BASDAI (p<0.01) and ASAS-HI (p=0.032) significantly reduced; rates of ASDAS-CRP inactive disease and LDA were 15.2% and 26.1%, respectively; 14% of patients had a ≥50% improvement in baseline BASDAI. After 3 months of golimumab treatment, there was a decrease in the prevalence of enthesitis (32.9% to 16.5%), nail (17.6% to 12.9%) and skin psoriasis (42.4% to 34.1%) in PsA patients; the frequency of extra articular manifestations tended to decrease also in axSpA patients. Preliminary results of the GO-BEYOND-Italy study showed a good short-term effectiveness of golimumab in RA, PsA and axSpA after TNFi failure. Salvatore D'Angelo Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Enrico Tirri Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Angela Maria Giardino Employee of: MSD Italia, Marco Matucci-Cerinic Speakers bureau: BMS, Pfizer, Actelion, Consultant of: Eli-Lilly, Celgene, Chemomab, CSL Behring, Grant/research support from: BMS, Pfizer, Celgene, CSL Behring, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Leonardo Santo: None declared., francesco ciccia: None declared., Bruno Frediani: None declared., Marcello Govoni: None declared., Francesca Bobbio Pallavicini: None declared., Rosa Daniela Grembiale: None declared., Andrea Delle Sedie: None declared., Stefania Cercone Employee of: MSD Italia, RITA MULE': None declared., Francesco Paolo Cantatore Speakers bureau: Pfizer, Sanofi Genzyme and Roche, Consultant of: Pfizer, Sanofi Genzyme and Roche outside this work., Rosario Foti: None declared., Elisa Gremese: None declared., Roberto Perricone: None declared., Fausto Salaffi: None declared., Ombretta Viapiana Speakers bureau: Novartis, UCB, Abbvie, MSD, Fresenius kabi, Gilead, Biogen, Consultant of: Novartis, Abbvie, Fresenius kabi, Gilead, Biogen, Alberto Cauli Speakers bureau: Abbvie, Alfa-Sigma, BMS, Celgene, Galapagos, Glaxo, MSD, Novartis, Janssen, Pfizer, Sanofi, UCB, Consultant of: Abbvie, Alfa-Sigma, BMS, Celgene, Galapagos, Glaxo, MSD, Novartis, Janssen, Pfizer, Sanofi, UCB, Rorberto Giacomelli: None declared., Luisa Arcarese: None declared., Giuliana Guggino Speakers bureau: Novartis, Celgene, Abbvie, Sandoz, Eli Lilly, Pfizer, Jansen, ROMUALDO RUSSO: None declared., Domenico Capocotta: None declared., Francesca Nacci: None declared., Maria Grazia Anelli: None declared., valentina picerno: None declared., Florenzo Iannone Speakers bureau: Pfizer, AbbVie, Janssen, Celgene, Novartis, MSD, BMS, UCB, Roche, Consultant of: Pfizer, AbbVie, Janssen, Celgene, Novartis, MSD, BMS, UCB, Roche outside this work. Table 1Effectiveness of golimumab at 3 months in the GO-BEYOND-Italy studyRheumatoid arthritis (n=38)Psoriatic arthritis (n=91)Axial spondyloarthritis (n=64)DAS28-CRP, mean (SD)n=27DAS28-CRP, mean (SD)n=47ASDAS-CRP, mean (SD)n=44V0 / V14.05 (0.8) / 3.10* (1.0)V0 / V13.66 (1.0) / 2.79* (1.2)V0 / V12.86 (1.0) / 2.33* (1.0)V1: DAS28-CRP disease activity, n (%)n=27V1: EULAR response, n (%)n=33V1: ASDAS-CRP disease activity, n (%)n=46Remission8 (29.6)Good16 (48.5)Inactive disease7 (15.2)Low disease activity6 (22.2)Moderate10 (30.3)Low disease activity12 (26.1)Moderate disease activity13 (48.1)No response7 (21.2)High disease activity22 (47.8)Very high disease activity5 (10.9)V1: EULAR response, n (%)n=23V1: MDA, n (%)n=75Good7 (30.4)Yes21 (28.0)BASDAI, mean (SD)n=50Moderate8 (34.8)V0 / V15.99 (2.1) / 4.92 (2.3)*No response8 (34.8)V1: BASDAI50, n (%)7 (14.0)ASAS-HI, mean (SD)n=48V0 / V110.67 (3.8) / 9.68 (4.6)^*p value for the difference from V0 <0.01. ^ p for the difference from V0=0.032Abbreviations: ASDAS: Ankylosing Spondylitis Disease Activity Score; ASAS-HI: Assessment of SpondyloArthritis international society Health Index; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CRP: C-reactive protein; DAS: disease activity score; EULAR: European League Against Rheumatism; MDA: Minimal Disease Activity; SD: standard deviation; V0: baseline; V1: 3 months evaluation.