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To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast’s safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0–29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient’s health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

PURPOSE To examine the impact of golimumab, on work productivity, activity limitation, and quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS This real-world, multicenter, prospective study consecutively enrolled adult consented work-active patients with axSpA or PsA, newly initiated on golimumab as per the approved label. Prior receipt of > 1 prior biologic, or switching from another tumor-necrosis factor inhibitor due to primary non-response or safety reasons was not allowed. The Work Productivity and Activity Impairment-Specific Health Problem and the EuroQol 5-Dimensions (EQ-5D)-5-Level instruments were completed by the patients to assess the impact of golimumab on work productivity and activity impairment, and generic QoL, respectively. RESULTS Overall, 121 eligible patients (mean age: 45.4 years; median disease duration: 11.3 months), 51 diagnosed with PsA and 70 with axSpA, were enrolled by 19 rheumatologists. Over a 11.9-month median observation period

Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in > 2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in ≥ 2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs; 18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4]; n = 6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1]; n = 2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7]; n = 5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. G. Katsifis: Consultancies; Abbvie, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, Sobi, UCB. Honoraria; AbbVie, Aenorasis, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, UCB. A. Kandili: None. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Janssen. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. P. Goupille: Consultancies; AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Biogen, BMS, Chugai, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. N. Maiden: Member of speakers’ bureau; Eli-Lilly, UCB. M. Aassi: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Objectives The efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA. Methods CIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses. Results A total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s.d.) change in BASDAI was −2.9 (2.3; n = 439); for r-axSpA and nr-axSpA, it was −2.9 (2.2; n = 301) and −2.8 (2.4; n = 137), respectively (P Conclusion Improvements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns.

ObjectivesTo evaluate 6-month effectiveness of ustekinumab versus tumour necrosis factor inhibitor (TNFi), analysing predictors of low disease activity (LDA)/remission.MethodsPsABio is a prospective, observational cohort study of patients with psoriatic arthritis (PsA) at 92 sites in eight European countries, who received first-line to third-line ustekinumab or a TNFi. Comparative achievement at 6 months of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) LDA/remission, and minimal disease activity (MDA)/very LDA using propensity score (PS)-adjusted multivariate logistic regression was assessed.ResultsIn the final analysis set of 868 participants with 6-month follow-up data (ustekinumab, n=426; TNFi, n=442), with long-standing disease and a high mean cDAPSA score (31.0 vs 29.8, respectively), proportions of patients in ustekinumab/TNFi treatment groups achieving cDAPSA LDA at 6 months were 45.7%/50.7%. cDAPSA remission was achieved in 14.9%/19.2%, and MDA in 26.4%/30.8% of patients. PS-adjusted odds ratios (OR; 95% confidence interval (CI)) of reaching cDAPSA LDA and MDA were 0.73 (0.46 to 1.15) and 0.87 (0.61 to 1.25) with ustekinumab versus TNFi, indicating no significant difference. High baseline body mass index or high cDAPSA were associated with a lower chance (OR (95% CI)) of reaching cDAPSA LDA with TNFi (0.94 (0.89 to 0.99) and 0.64 (0.52 to 0.79), respectively). Predictive factors were similar to previously published evidence, with cDAPSA and 12-item Psoriatic Arthritis Impact of Disease scores and chronic widespread pain at baseline appearing as new risk factors for unfavourable outcome. Safety data were similar between groups.ConclusionTreatment targets were reached similarly after 6 months of treatment with ustekinumab and TNFi.

Objectives To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. Methods A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. Results Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. Conclusions In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.

Background The additional benefit of methotrexate (MTX) as a concomitant treatment in PsA has not been fully elucidated for TNF inhibitors (TNFi) and no real-world data on this currently exist for ustekinumab (UST). We investigated the additive effect of MTX on the ability to reach composite treatment targets beyond monotherapy with UST or TNFi, and the ability to improve patient-reported outcomes in a real-world clinical setting in 8 European countries. Methods The PsABio study (NCT02627768) evaluates persistence, effectiveness and tolerability of 1st, 2nd or 3rd-line UST or TNFi in patients with PsA. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (LDA) or remission, as well as the patient acceptable symptom state (PASS; score ≤4) of the 12-item Psoriatic Arthritis Impact of Disease questionnaire (PsAID-12) were evaluated. Here we present 6-month follow-up data using intention to treat (ITT) analysis; patients who stopped/switched initial treatment were imputed as non-responders. The effect of MTX co-therapy was investigated within UST and TNFi cohorts, as well as between the cohorts, using multivariate logistic regression including interaction terms, and propensity score (PS) analysis to adjust for imbalanced, potentially prognostic, baseline covariates. Results Of 930 patients, data was available for 868 ITT patients, including patients who switched/stopped before 6 months (UST: n = 28/426 [6.6%], TNFi: n = 44/442 [10.0%]). At baseline there were no relevant differences in demographics and disease activity, however there were significant differences in skin involvement as well as csDMARD and NSAID exposure. Co-therapy with MTX did not increase the likelihood of achieving any of the outcomes in either the UST or TNFi cohorts (Table 1). After PS adjustment, co-treatment with MTX did not influence treatment effects differently when added to UST compared with TNFi. concomitant use of csDMARDs other than MTX yielded very similar results. Conclusion In a real-world setting, concomitant treatment with MTX in addition to UST or TNFi was not associated with enhanced effects across a broad variety of disease outcomes, including disease activity, disease impact, and skin involvement within or between treatment cohorts, after PS adjustment for baseline confounders. Disclosures S. Siebert: Consultancies; AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, Novartis. Grants/research support; Pfizer, Janssen, BMS, Celgene, UCB, Boehringer Ingelheim. E. Gremese: Consultancies; AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, Pfizer. P. Bergmans: Shareholder/stock ownership; Johnson & Johnson. Other; Employee of Janssen. K. de Vlam: Consultancies; Johnson & Johnson. B. Joven-Ibáñez: Member of speakers’ bureau; Celgene, Novartis, MSD, Pfizer, AbbVie, Janssen. G. Katsifis: None. T.V. Korotaeva: Consultancies; Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, UCB, Lilly, Novartis-Sandoz. W. Noël: Other; Employee of Janssen. C. Selmi: None. P.P. Sfikakis: None. P. Smirnov: Other; Employee of Janssen. E. Theander: Other; Employee of Janssen. M.T. Nurmohamed: Grants/research support; Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Lilly, Sanofi, Celgene. L. Gossec: Honoraria; AbbVie, Celgene, Janssen, Lilly, Novartis-Sandoz, Pfizer, Sanofi, UCB. Grants/research support; Pfizer. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, GlaxoSmithKline, ILTOO Pharma, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. Grants/research support; AbbVie, Janssen, Lilly, MSD, Pfizer, Roche.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by excessive systemic inflammation, caused by uncontrolled activation of lymphocytes and macrophages, which secrete increased amounts of cytokines. HLH may be caused by gene mutations (primary HLH) or associated with malignancy, immunodeficiency, infection or autoimmune disease (secondary HLH). A 58-year-old woman with seropositive rheumatoid arthritis (RA) presented with fever, ulcers on the left foot and in the intergluteal cleft and increased inflammation markers. Clinical and laboratory evaluation, combined with findings from intra-arterial digital subtraction angiography of the lower limbs, pointed towards the diagnosis of vasculitis. Intravenous administration of low-dose cyclophosphamide resulted in recession of fever and decrease of inflammation markers. However, the patient later developed pancytopenia, hepatomegaly, hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia, while bone marrow aspiration demonstrated hemophagocytosis. The diagnosis of HLH was established. An extensive workup excluded malignancies, systemic infections and immunodeficiencies. HLH in our patient was attributed to activation of RA and presentation of vasculitis. Treatment with corticosteroids and intravenous immunoglobulin led to resolution of fever, correction of pancytopenia and complete healing of the ulcers. Timely diagnosis and treatment of HLH is highly important for a favorable outcome for the patients. Treatment of secondary HLH associated with autoimmune diseases involves corticosteroids and/or other immunomodulatory agents, such as intravenous immunoglobulin.

Background Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNF with an established efficacy and safety profile in axial spondyloarthritis (axSpA) in clinical trial settings.1 Objectives To report CZP effectiveness and safety in patients (pts) with axSpA, including ankylosing spondylitis (AS; radiographic axSpA) and non-radiographic (nr-) axSpA subpopulations, in routine clinical practice in Europe. Methods CIMAX (NCT02354105) was a non-interventional multicentre prospective cohort study observing CZP treatment response and safety over 12 months in a real-world clinical cohort of axSpA pts newly prescribed CZP. The primary outcome was change from baseline (CFB) in Bath ankylosing Spondylitis Disease activity index (BASDAI) to Week (Wk) 52 in pts with available data, with additional outcomes pertaining to effectiveness and safety. Outcomes were evaluated for aS and nr-axSpA subpopulations (diagnosed according to local practice). Pts who received ≥1 dose CZP were followed up for adverse events (AEs) (Safety Set [SS]); those with baseline and ≥1 post-baseline BASDAI assessment were included in the effectiveness analyses (Full analysis Set [FAS]). Outcomes are reported using observed case data with no imputation. Results 682 axSpA pts were enrolled from 101 European sites, of whom 490 (71.8%) completed the study. Of those enrolled, 672 formed the SS (AS: 469; nr-axSpA: 201) and 564 the FAS (AS: 384; nr-axSpA: 179); 2(SS)/1(FAS) pts with unconfirmed aS/nr-axSpA were included in the overall axSpA population. 27.5% (185/672[SS]) axSpA pts had previous anti-TNF exposure (AS: 31.1% [146/469]; nr-axSpA: 18.4% [37/201]). BASDAI data were available for 77.8% (439/564) pts at Wk52. In pts with available data, all clinical outcomes were improved at Wk52 in both subpopulations (Table). At baseline, the mean BASDAI was 6.1. At Wk52, the mean BASDAI CFB in pts with available data (n=439) was −2.9 (AS: −2.9 [n=301]; nr-axSpA: −2.8 [n=137]). For pts with and without prior anti-TNF exposure, BASDAI at baseline was 6.1 in both groups (n=165 vs n=399, respectively), and at Wk52, the mean BASDAI CFB was −2.6 (n=127) vs −3.0 (n=312) (AS: −2.7 vs −3.0; nr-axSpA: −2.2 vs −3.0). In the SS, 37.9% (255/672) pts experienced aEs; 20.7% (139/672) experienced drug-related aEs and 6.3% (42/672) serious aEs (1.8% [12/672] reported serious infections); these data were comparable between aS and nr-axSpA (Table). Conclusion This is the first multicentre European study to evaluate CZP effectiveness and safety in both axSpA subpopulations in routine practice. Improvements were observed in all signs and symptoms in pts who remained on treatment to Wk52; >70% of those enrolled completed the study. No new safety signals were identified following application of CZP to real-world rheumatological practice. References [1] van der Heijde D. Rheumatology (Oxford)2017;56:1498–509. Acknowledgement We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Jessica Patel, Costello Medical, UK. Disclosure of interests Xenofon Baraliakos Grant/research support from: abbVie, Boehringer ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer inc, Roche and UCB, Grant/research support from: abbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: abbVie, Bristol-Myers Squibb, Boehringer ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: abbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Torsten Witte Consultant for: UCB Pharma, Luc De Clerck Grant/research support from: abbvie, MSD, Roche, Pfizer, Bruno Frediani: None declared, Eduardo Collantes-Estevez Consultant for: UCB Pharma, MSD, abbVie, Novartis, Janssen, Gkikas Katsifis Consultant for: UCB Pharma, Janssen, abbvie, Novartis, MSD, aenorasis, Genesis Pharma, Pfizer, Roche, Brenda VanLunen Employee of: Employee of UCB Pharma, Elisabeth Kleine Employee of: Employee of UCB Pharma, Bengt Hoepken Employee of: Employee of UCB Pharma, Nicola Goodson Grant/research support from: Novartis, Speakers bureau: abbVie, Janssen, UCB Pharma

Background Vaults are the largest nonicosahedral cytosolic ribonucleoprotein particles ever described, with a mass of 13Mda. They are ranging from 10 4 to 10 7 particles per cell, with an enormous interior volume, large enough to encapsulate hundreds of proteins or RNAs. Their functions have not been fully elucidated although various studies suggest that they are involved in multidrug resistance, nucleocytoplasmic transport, and intracellular signalling. Vaults are barrel-shaped particles comprising a 78-mer of major vault protein (MVP) molecules, 2 other proteins TEP1 and VPARP and a small untranslated RNA (vRNA). TEP1 shares sequence similarity with Ro autoantigen, a common target of autoantibodies, while vault RNA is complexed with another autoantigen the La protein. In this study, we sought to evaluate the levels of MVP in sera of patients with RA relative to healthy individuals. Materials and methods MVP levels were quantified in serum of 46 patients with rheumatoid arthritis, 10 patients with early rheumatoid arthritis (ERA), 17 patients with osteoarthritis (OA) and 22 healthy individuals, using a MVP sandwich ELISA. We also measured the levels of RF, CRP and anti-CCP in the same serums. Results MVP levels were found elevated in ERA (100% positive, 89.5% specificity) and RA (73.9% positive, 89.5% specificity), whereas the levels of MVP were found reduced in OA (17.6% positive) and normal subjects (4.5% positive). Notably, 50% of ERA patients were anti-CCP and RF negative and MVP positive. MVP levels were similar in RA and ERA patients but lower from OA patients and normal subjects (p Conclusions MVP levels are remarkably elevated in both patients with RA or ERA, having the potential to serve as a new diagnostic marker for early detection of rheumatoid arthritis.