Explore the vast range of titles available.

Objectives: To assess the risk of lymphoproliferative disease or other malignancy (standardised incidence ratios (SIRs)), in patients with primary Sjögren’s syndrome according to the American-European Consensus Criteria (AECC), compared with patients with sicca syndrome (non-AECC) and the background population. To identify predictors of malignancy and describe lymphoma types and survival probabilities. Methods: A linked register study using information from the Malmö Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for calculation of SIRs was carried out. Detected lymphomas were reclassified according to the WHO classification. Cox regression analysis was used to study the predictive value of clinical, laboratory, and histological findings at the time of diagnosis. Results: 507 patients with a median follow up of 8 years (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI)) for malignancies in total and for non-Hodgkin’s lymphomas (NHL) were 1.42 (0.98 to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was 0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18, 95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell ratio ⩽0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse large B cell lymphomas. Conclusion: A 16-fold increased risk for development of NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for developing lymphoma.

Guselkumab (GUS), a selective monoclonal antibody targeting the interleukin-23p19 subunit, has demonstrated efficacy in 2 pivotal Ph3 psoriatic arthritis (PsA) studies (DISCOVER-1,1 DISCOVER-22). Evaluate GUS efficacy and safety in PsA patients (pts) with inadequate response (IR) to tumor-necrosis-factor inhibition (TNFi) through Week24 (W24) of the Ph3b COSMOS study. In this randomized, double-blind, placebo (PBO)-controlled trial, 285 pts with active PsA (≥3 swollen & ≥3 tender joints) who demonstrated lack of benefit or intolerance to 1-2 TNFi were randomized 2:1 to subcutaneous GUS 100mg (n=189) or PBO (n=96) at W0, W4, then every 8 weeks (Q8W) through W44 (with PBO crossover to GUS at W24). At W16, pts who met early escape (EE) criteria (<5% improvement in both tender & swollen joint counts) also could switch from PBO to GUS. The primary efficacy endpoint was ACR20 response at W24 among randomized, treated pts. Pts missing ACR20 data at W24 or who met treatment failure criteria (including meeting EE criteria at W16) were considered nonresponders (NRs). Subgroup analyses were performed to assess consistency of primary treatment effect based on demographics, disease characteristics, and medication use at baseline. Prespecified sensitivity analyses included ‘Per-Protocol’ (PP) (excluded pts with major protocol deviations) and ‘EE-Correction’ (included pts incorrectly routed to EE) analyses. Adverse events (AEs) were summarized by treatment received. Baseline characteristics were similar across GUS and PBO pts, though a higher proportion of females and more severe joint symptoms were seen in the GUS group. At W24, 44.4% of GUS vs 19.8% of PBO pts achieved ACR20 (p<0.001) (Figure). GUS was superior to PBO for all major secondary endpoints. Efficacy was consistent across subgroups defined by baseline characteristics, including in pts who discontinued prior TNFi use due to inadequate efficacy (84% GUS vs 81% PBO) and safety (16% GUS vs 19% PBO) (Table). 20 pts (12 GUS, 8 PBO) were incorrectly routed to EE. Results of PP (48.8% vs 23.8%) and EE-correction (48.1% vs 19.8%) sensitivity analyses were consistent with the primary analysis (Figure). AEs were similar between GUS- and PBO-treated pts (Table). In this Ph3b, placebo-controlled study of PsA pts with IR to 1-2 TNFi, GUS 100 mg Q8W elicited a significantly higher ACR20 response rate vs. PBO at W24; results of prespecified sensitivity and subgroup analyses were consistent. GUS safety in TNF-IR PsA pts through W24 is consistent with the favorable GUS safety profile in psoriasis and biologic-naïve PsA pts.3 [1]Deodhar A. Lancet 2018;391: 2213–24. [2]Mease PJ. Lancet 2020;395: 1126–36. [3]Guselkumab Prescribing Information. Janssen Biotech, Inc. Laura C Coates Consultant of: AbbVie, Amgen, Biogen, BMS, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, Sanofi, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Georg Schett: None declared, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB [Display omitted] Table 1Baseline characteristics of, and adverse events reported by, randomized and treated COSMOS ptsGUS 100 mg Q8W (N=189)PBO (N=96)Age, y4949Sex, Female54%46%Duration of PsA, y8.38.7Body mass index, kg/m22931aSwollen (0-66) / tender (0-68) joint count10 / 219 / 18Pt pain / Pt global arthritis / Physician global disease, 0-10 cm VAS6.5 / 6.5 / 6.96.0 / 6.2 / 6.4Health Assessment Questionnaire-Disability Index, 0-31.3b1.2C-reactive protein, mg/dL1.2b1.2Methotrexate use at baseline56%53%Psoriatic body surface area, %17.913.4Number of prior TNFi: 1 / 288% / 12%89% / 11%Reason for prior TNFi discontinuation: Efficacy / Safety84% / 16%*81% / 19%*Pts with ≥1 AE / SAE37% / 3%48% / 3%Pts with ≥1 infection / serious infection18% / 0%20% / 0%Pts with ≥1 AE leading to study agent discontinuation2%2%Pts with ≥1 malignancy0.4%0Pts with ≥1 injection-site reaction2%1%Data shown are mean or %. aN=95; bN=188. *Missing for 1 pt. SAE – serious adverse events; VAS – visual analog scale

Psoriatic arthritis (PsA) is characterised by musculoskeletal symptoms, and patients (pts) with PsA usually experience psoriasis concurrently. Real-world data reflecting impact of skin symptoms on PsA disease burden are limited. Analyse effectiveness of ustekinumab (UST) and tumour necrosis factor inhibitor (TNFi) therapy on extent of skin involvement, and the impact this has on PsA disease burden and drug persistence. PsABio (NCT02627768) is a prospective, observational study of 1st/2nd/3rd-line UST or TNFi treatment in PsA in 8 European countries. Extent of skin involvement was categorised as body surface area (BSA): clear/almost clear; <3% but not clear/almost clear; 3–10%; or >10%. Pt-reported disease impact was evaluated by PsAID-12, including assessment of two skin-related domains (D): D3 (skin problems, including itching) and D10 (embarrassment and/or shame because of appearance). Estimated persistence at 1 year was assessed across baseline (BL) BSA categories. At BL, significantly more pts receiving UST than TNFi had BSA >10% (Figure 1). BL disease impact (PsAID-12) was worse in pts with BSA >10% than <3% in D3, D10 and total (non-overlapping 95% CIs suggest significance) (Table 1). BSA improved from BL to 1 year with both treatments. At 1 year, 64% of pts in both groups had clear/almost clear skin and only 3% had BSA >10% (Figure 1). At 1 year, both treatments significantly reduced disease impact (PsAID-12 total), and D3 and D10 scores, irrespective of BL BSA category, but most markedly in pts with higher BL BSA (Table 1). Worse BL psoriasis was generally associated with longer persistence for both treatments; however, at 1 year, pts with BSA >10% had significantly shorter persistence with TNFi (mean [95% CI]: 361 [336; 387] days) than with UST (410 [394; 426] days). In PsA, interleukin-12/23 inhibition (UST) and TNFi therapy in routine care rapidly and substantially reduced extent of skin involvement and related disease impact. Pts with highest BL skin involvement had significantly longer drug persistence with UST than with TNFi. Together, PsABio data suggest that successful treatment of skin involvement in PsA with biologics reduces disease burden and may improve persistence, especially in pts with worse BL psoriasis. This study was funded by Janssen. 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, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Consultant of: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Galapagos, Johnson & Johnson, Novartis, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared., Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, Novartis, MSD, Pfizer, Wim Noel Employee of: Janssen, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, Laure Gossec Consultant of: AbbVie, Amgen, Bioepis, Biogen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi. [Display omitted] Table 1PsAID-12 scores at BL and change from BL scores at 6 months and 1 year, by BL BSA categoryMean (95% CI)Domain 3(skin problems, including itching)Domain 10(embarrassment and/orshame because of appearance)Total PsAID-12USTTNFiUSTTNFiUSTTNFiPsAID-12 score at BL by BL BSA<3%4.2 (3.7; 4.8)3.1 (2.7; 3.6)3.9 (3.3; 4.4)3.1(2.6; 3.6)5.7(5.3; 6.0)5.0 (4.6; 5.3)3–10%6.4 (5.9; 6.8)5.8 (5.3; 6.3)4.1 (3.5; 4.7)4.5 (3.9; 5.1)5.4 (5.1; 5.8)5.8 (5.4; 6.1)>10%7.9 (7.5; 8.3)6.7 (6.0; 7.5)6.1 (5.4; 6.8)5.8 (4.8; 6.8)6.2 (5.7; 6.6)6.1 (5.6; 6.7)Change from BL in PsAID-12 score at 6 months by BL BSA<3%-1.5 (-2.1; -0.9)-0.8 (-1.3; -0.3)-1.5 (-2.0; -0.9)-1.2 (-1.6; -0.7)-1.6 (-2.0; -1.2)-1.9 (-2.2; -1.5)3–10%-3.2 (-3.8; -2.7)-2.4 (-3.0; -1.9)-1.9 (-2.5; -1.3)-2.0 (-2.5; -1.5)-2.0 (-2.4; -1.6)-2.4 (-2.8; -2.0)>10%-4.2 (-4.9; -3.6)-2.5 (-3.2; -1.9)-2.9 (-3.5; -2.2)-1.6 (-2.4; -0.8)-2.4 (-2.8; -2.0)-2.2 (-2.7; -1.7)Change from BL in PsAID-12 score at 1 year (LOCF) by BL BSA<3%-1.5 (-2.1; -0.9)-0.8 (-1.3; -0.3)-1.6 (-2.2; -1.1)-1.2 (-1.7; -0.7)-1.6 (-2.0; -1.2)-1.9 (-2.3; -1.5)3–10%-3.5 (-4.0; -2.9)-3.2(-3.7; -2.7)-2.0 (-2.6; -1.4)-2.5 (-3.0; -2.0)-2.2 (-2.6; -1.7)-3.0 (-3.4; -2.6)>10%-4.9 (-5.5; -4.3)-3.1 (-4.0; -2.3)-3.5 (-4.2; -2.8)-2.7 (-3.7; -1.8)-2.9 (-3.4; -2.4)-2.9 (-3.5; -2.2)PsAID-12 total score ≤4 is considered a patient-acceptable symptom state.BL, baseline; BSA, body surface area; CI, confidence interval; LOCF, last observation carried forward; PsAID-12, 12-item Psoriatic Arthritis Impact of Disease questionnaire; TNFi, tumour necrosis factor inhibitor; UST, ustekinumab

Psoriatic arthritis (PsA) negatively impacts patients' (pts) quality of life (QoL), with a high burden of pain, fatigue and psychological distress. The 12-item Psoriatic Arthritis Impact of Disease questionnaire (PsAID-12) is a validated measure of pt-reported disease impact. To analyse PsAID-12 score changes in the overall population and specific subgroups of interest, and assess correlation of these changes using Health Assessment Questionnaire Disability Index (HAQ-DI). PsABio (NCT02627768) is a multinational, prospective, observational study in pts with PsA receiving ustekinumab (UST) or a tumour necrosis factor inhibitor (TNFi) as a 1st/2nd/3rd-line biologic. Descriptive statistics, including 95% CI, are presented at baseline (BL) and 1 year. Linear regression, including propensity score (PS) adjustment for BL covariates, was used to compare change in PsAID-12 total from BL to 1 year between treatments. The relationship between changes in PsAID-12 and HAQ-DI was investigated using Spearman's correlation. Data were available for 438 UST and 455 TNFi pts. From BL to 1 year, significant improvements were seen in total PsAID-12 scores and in all domains with both treatments (Figure 1). PS-adjusted treatment comparison showed no difference in total PsAID-12 improvement (regression coefficient [95% CI]: 0.14 [-0.22; 0.51], p=0.4433), or in any domain, except skin problems, which improved significantly more with UST than TNFi (-0.55 [-1.04, -0.06], p=0.0277). Improvements in PsAID-12 and HAQ-DI showed strong positive correlation with both treatments (UST: r=0.63, p<0.0001; TNFi: r=0.70, p<0.0001). Effectiveness was demonstrated with UST and TNFi in subgroups of interest, including biologic treatment line, sex and psoriasis extent (Table 1. next page). Treatment with IL-12/23 (UST) or TNF inhibitors significantly improved pt-reported disease impact at 1 year. PS-adjusted PsAID-12 improvements did not differ significantly between treatments, except skin problems (better with UST). Improvements in disease impact and physical functioning (HAQ-DI) were strongly correlated, emphasising the effect of these biologics on QoL in PsA pts. This study was funded by Janssen. Laure Gossec Consultant of: AbbVie, Amgen, Bioepis, Biogen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Galapagos, Johnson & Johnson, Novartis, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared, Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, MSD, Novartis, Pfizer, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Lilly, Janssen, MSD, Novartis, Novartis-Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, Biocad, Lilly, Janssen, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Wim Noel Employee of: Janssen, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, Pfizer, MSD, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, 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. [Display omitted] Table 1PsAID-12 scores by BL characteristic subgroupMean (95% CI)USTTNFiBLUnadjusted change from BL at 1 year (LOCF)BLUnadjusted change from BL at 1 year (LOCF)Biologic line1st5.51(5.19; 5.82)-2.14(-2.49; -1.79)5.44(5.15; 5.72)-2.41(-2.72; -2.09)2nd6.05(5.69; 6.41)-2.14(-2.55; -1.72)5.57(5.19; 5.95)-2.37(-2.79; -1.94)3rd5.84(5.33; 6.35)-1.81(-2.45; -1.17)5.34(4.52; 6.15)-1.89(-2.62; -1.16)Sex*Male5.27(4.95; 5.59)-2.35(-2.70; -1.99)4.89(4.56; 5.23)-2.49(-2.83; -2.15)Female6.14(5.86; 6.43)-1.86(-2.20; -1.52)5.95(5.67; 6.23)-2.20(-2.53; -1.87)EnthesitisYes5.95(5.66; 6.24)-2.19(-2.51; -1.86)5.89(5.61; 6.17)-2.65(-2.98; -2.31)No5.51(5.19; 5.83)-1.98(-2.36; -1.59)4.99(4.65; 5.32)-2.02(-2.35; -1.68)Psoriasis BSA, %<35.66(5.32; 6.00)-1.60(-2.03; -1.18)4.97(4.63; 5.31)-1.89(-2.25; -1.52)3–105.44(5.05; 5.83)-2.16(-2.59; -1.74)5.78(5.43; 6.14)-2.99(-3.38; -2.59)>106.15(5.70; 6.60)-2.93(-3.43; -2.43)6.13(5.55; 6.71)-2.86(-3.49; -2.23)Joint involvement†Mono/oligoarticular5.07(4.56; 5.58)-1.96(-2.47; -1.45)4.82(4.38; 5.25)-2.18(-2.66; -1.70)Polyarticular5.98(5.75; 6.22)-2.21(-2.51; -1.92)5.78(5.52; 6.04)-2.47(-2.75; -2.18)FiRST score*<55.15(4.87; 5.44)-2.18(-2.50; -1.87)5.10(4.83; 5.36)-2.44(-2.71; -2.16)≥56.72(6.43; 7.00)-1.95(-2.38; -1.53)6.49(6.15; 6.83)-2.09(-2.57; -1.61)*At BL, female pts and pts with FiRST score ≥5 (chronic widespread pain) were significantly more impacted than male pts and pts with FiRST score <5, and remained significantly more impacted at 1 year. †Polyarticular pts were significantly more impacted at BL, but not 1 year.BSA, body surface area; CI, confidence interval; FiRST, Fibromyalgia Rapid Screening Tool; LOCF, last observation carried forward

Sex-related differences in biologic treatment of psoriatic arthritis (PsA) have been insufficiently studied in a real-world setting. To evaluate impact of sex on PsA, treatment effectiveness and persistence after 1 year of biologic treatment. PsABio (NCT02627768) is a multinational, prospective real-world study in PsA with ustekinumab (UST) or TNF inhibitor (TNFi) as 1st/2nd/3rd-line biologic. Males and females were compared for disease activity and patient-reported outcomes. Descriptive statistics including 95% CI at baseline (BL) and 12 (±3) months (LOCF) follow-up are presented. Intra-sex comparisons between UST and TNFi cohorts were done by logistic regression analysis, with propensity score adjustment for imbalanced BL covariates and non-response imputation for stopping/switching biologic drugs. Among 494 females and 399 males, age and disease duration were similar. However, differences in disease characteristics at BL were considerable: females had worse scores than males for cDAPSA, HAQ-DI, EQ5D VAS, PsAID-12, pain and comorbidities. At 1 year, similar improvements from BL were observed between sexes, but females remained in a worse health state than males (Table). Achievement of composite endpoints MDA (including VLDA) and cDAPSA LDA (including remission) was high overall (38.6% and 61.5%, respectively), but reached by >2-fold and 3-fold more males than females, respectively. HAQ-DI scores remained worse for females at 1 year (0.95) than for males at BL (0.93). Enthesitis resolution was achieved in 46% of females and 75% of males. No significant differences in effectiveness of UST vs TNFi were detected between sexes (Figure). Kaplan–Meier estimated drug persistence was significantly better in males than females (log-rank p=0.0007). There was no intra-sex difference between UST or TNFi in risk of stopping/switching in males or females. These real-world data from PsABio on sex differences with biologic treatment suggest that females generally start biologics in a worse PsA state than males. Although treatment improvements were similar between sexes, females remained in worse health at 1 year, and stopped/switched biologic earlier. More comprehensive treatment before severe disease manifestations evolve may improve management in females. This study was funded by Janssen [Display omitted] Irene van der Horst-Bruinsma Consultant of: AbbVie, Lilly, MSD, Novartis, UCB, Grant/research support from: AbbVie, MSD, Pfizer, UCB, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Arno Van Kuijk Consultant of: AbbVie, Janssen, LEO Pharma, Novartis, Grant/research support from: Janssen, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Johnson &Johnson, Novartis Galapagos, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared, Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, MSD, Novartis, Pfizer, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Consultant of: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Wim Noel Employee of: Janssen, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, 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, Consultant of: AbbVie, AstraZeneca, Lilly, Novartis, Roche, 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 Table 1Patient and disease characteristics at BL and 1-year by sexBL femaleBL male1-year LOCF female1-year LOCF maleBiologic line, %1st4655N/AN/A2nd34333rd2013Co-treatment, %MTX37.434.3N/AN/ACorticosteroids34.632.1NSAIDs59.964.4Antidepressant7.92.5Comorbidities, %N/AN/ACardiovascular69.059.4metabolic syndrome40.131.7Obesity35.223.7Anxiety/depression12.67.5Smoking status, %N/AN/ANever54.941.9Past16.826.6Current22.724.3Unknown5.77.3Joint counts, nSwollen 666.1 (5.4; 6.9)5.6 (4.7; 6.4)2.2 (1.7; 2.6)1.3 (1.0; 1.6)Tender 6813.2 (12.0; 14.4)10.0 (8.9; 11.1)6.0 (5.2; 6.7)3.6 (2.9; 4.3)cDAPSA score, mean (95% CI)cDAPSA, %32.5 (30.5; 34.4)26.9 (24.9; 29.0)15.9 (14.5; 17.2)10.3 (9.0; 11.6)Remission1.0 (0.3; 2.6)4.0 (2.1; 6.7)17.8 (14.1; 22.0)37.7 (32.4; 43.2)Low6.7 (4.4; 9.7)15.0 (11.3; 19.4)33.0 (28.3; 37.9)36.5 (31.3; 42.0)Moderate38.9 (34.0; 44.0)42.6 (37.2; 48.2)34.3 (29.6; 39.2)16.9 (13.0; 21.4)High53.4 (48.2; 58.4)38.3 (33.0; 43.9)14.9 (11.6; 18.9)8.9 (6.0; 12.5)MDA2.3 (1.0; 4.3)7.7 (5.1; 11.2)27.5 (23.1; 32.1)52.2 (46.6; 57.7)VLDA0.00.9 (0.2; 2.6)6.2 (4.1; 9.0)19.7 (15.6; 24.3)HAQ-DI score1.31 (1.25; 1.37)0.93 (0.86; 1.00)0.95 (0.89; 1.02)0.53 (0.47; 0.59)PsAID-12 score6.1 (5.9; 6.3)5.1 (4.9; 5.3)4.0 (3.8; 4.3)2.7 (2.4; 2.9)EQ5D VAS score48.6 (46.6; 50.5)53.8 (51.6; 55.9)59.2 (56.9; 61.4)68.0 (65.5; 70.4)Enthesitis50.7 (45.9; 55.5)48.1 (42.8; 53.3)32.6 (28.3; 37.3)18.0 (14.1; 22.3)Dactylitis15.6 (12.4; 19.3)24.7 (20.4; 29.3)5.7 (3.8; 8.3)4.8 (2.9; 7.4)Data are % (95% CI) unless indicated otherwise. Bold data are significantly different (non-overlapping 95% CI).

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.

Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5 , the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P -values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P =2.5 × 10 −9 . The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

BackgroundPulmonary involvement is a recognized extra-glandular manifestation of primary Sjögren's syndrome (pSS). Recently, we demonstrated that chronic obstructive pulmonary disease (COPD) is common in patients with pSS, even in the absence of smoking (1).ObjectivesIn a nested case control study, we now investigate the predictive role of obstructive airway symptoms for development of pSS.MethodsIn two population-based surveys [Malmö Preventive Medicine (N=33346) and Malmö Diet & Cancer (N=30447), pulmonary function tests were performed. OAS was defined as either COPD (FEV1 <70% at inclusion) or a history of treatment of asthma/chronic bronchitis. Among survey participants, incident cases of pSS were identified. Four controls for each validated case, matched for sex, year of birth and year of screening, who were alive and free of pSS when the index person was diagnosed with pSS, were selected from the corresponding health survey database. Proportions with vs without a history of OAS or current smoking at inclusion in the health survey in pre-pSS individuals and controls were compared using χ2-test. The impact of OAS and smoking history on the risk of pSS was examined in conditional logistic regression analysis.ResultsSixty-three individuals (8% male, median age at inclusion 51 (29-72) years) were diagnosed with pSS a median of 98 months (3-329) after inclusion and fulfilled the 2002 AECC-criteria for pSS. ANA, RF, anti-Ro and anti-La were positive in 73%, 57%, 59% and 41% respectively. Focal sialadenitis with focus score ≥1 was found in 85%. At inclusion significantly more pre-pSS individuals had OAS compared to controls: 21% vs 8%, p=0.014. OR 3.1 (95% CI 1.3-7.5). While in healthy controls there was a clear association between current smoking and OAS (p=0.031), in pre-pSS individuals smoking did not influence the presence of OAS (p=0.45). In multivariate analysis, OAS and being non-smoker independently predicted development of pSS during follow-up.CasesControlsCrude OR (95% CI)Adjusted OR (95% CI)No OAS37 (79%)186 (92%)1 (ref)1 (ref)OAS10 (21%)16 (8%)3.1 (1.3–7.5)7.6 (2.4–23)*Non-smoker50 (83%)159 (63%)1 (ref)1 (ref)Current smoker10 (17%)92 (37%)0.26 (0.11–0.60)0.24 (0.09–0.63)***Adjusted for current smoking,**adjusted for OAS. ConclusionsPresence of obstructive airway symptoms in pre-pSS individuals increases the risk of pSS independently of smoking habits, while being current smoker seems to lower it. These data confirm results from our earlier cross-sectional and retrospective studies, both with regard to COPD and smoking (1,2). Airway inflammation, unrelated to smoking, may be a very early step in the development of pSS.ReferencesNilsson A. et al, J Rheumatol 2015; Jan 15. pii: jrheum.140370. [Epub ahead of print],Manthorpe R. et al. Ann Rheum Dis 2000; 59: 54-60Disclosure of InterestNone declared

BackgroundSmokers have increased risk of anti-CCP positive RA. In some diseases, such as Ulcerative colitis, Sarcoidosis and Parkinson's disease smoking seems beneficial or protective. In 2000 we described an inverse association between smoking and focal sialadenitis and anti-Ro/anti-La in pSS (1)ObjectivesTo investigate the effect of smoking on development of pSS in a nested case control study, based on two prospective health surveys.MethodsAmong participants in two population-based surveys [Malmö Preventive Medicine (N=33346) and Malmö Diet & Cancer (N=30447)], incident cases of pSS were identified. Four controls for each validated case, matched for sex, year of birth and year of screening, who were alive and free of pSS when the index person was diagnosed with pSS, were selected from the corresponding health survey database. Information on the time of onset of sicca symptoms had been independently recorded at the time of pSS diagnosis. Proportions with a history of never/former/current smoking in pre-pSS individuals and controls were compared using the χ2-test. The impact of smoking history on the risk of pSS was examined in conditional logistic regression analysis.ResultsSixty-three individuals (8% male, mean age at inclusion 51 (range 29-72) years) were diagnosed with pSS a median of 98 months (3-329) after inclusion and fulfilled the 2002 AECC-criteria for pSS. ANA, RF, anti-Ro and anti-La were positive in 73%, 57%, 59% and 41% respectively. Focal sialadenitis with focus score ≥1 was found in 85%.There was a significantly higher proportion of non-smokers among pre-pSS individuals compared to controls (85% vs 68%; p=0.004). Current smoking at inclusion was associated with a reduced risk of subsequent diagnosis of pSS (OR 0.26; 95% CI 0.11-0.60). The pattern of present–former–never smokers was different in cases and controls. The ratio present/former smoker was 0.3 among cases and 1.5 among controls (p<0.001). Being a former smoker was associated with an increased risk of pSS: OR 8.1; 95% CI 3.2-21 compared to current smokers. OR 4.1; 95% CI 1.8-10 compared to never smokers. Stopping smoking was not related to pSS symptoms (information available in 22 of 32 former smokers), as these appeared >5 years after smoking cessation in 91%. Anti-Ro or anti-La antibodies were found in similar frequencies among present, former and never smokers (80%, 56% and 56% respectively, p=0.28)ConclusionsSmoke cessation increases the risk of being diagnosed with pSS, while being a current smoker seems to lower it, confirming our former retrospective study. The impact of smoking and smoke cessation on development of autoimmunity should be further studied.ReferencesManthorpe R et al. Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjogren's syndrome? Ann Rheum Dis 2000; 59: 54-60Disclosure of InterestNone declared

Background Previously we reported that salivary gland ultrasonography (SGUS) using a simplified score1,2 is a specific but not a sensitive diagnostic method in primary Sjögren’s syndrome (pSS). The purpose of the present work is to analyse intra-observer validity and association with lymphoma risk factors. We have investigated 160 individuals, of which 30 have been studied at two time-points by the same investigator. Objectives To evaluate association with other lymphoma risk factors and intra-observer validity of SGUS in pSS. Methods SGUS was performed scoring parenchymal inhomogeneity as 0 = completely normal, 1 = slight abnormalities/few hypoechogenic areas, 2 = multiple hypoechogenic areas or 3 = many or confluent hypoechogenic lesions1. Assessment of EULAR SS Disease Activity Index (ESSDAI), presence of autoantibodies, immunoglobulin levels, complement levels, lymphocyte subtypes, parotid swelling and palpable purpura were assessed in pSS patients. Salivary gland biopsies were evaluated with regard to focal sialadenitis and germinal centre (GC)-like structures by routine staining and light microscopy, when available. Results Salivary glands of 105 pSS patients fulfilling the 2002 American European Consensus Criteria and of 56 controls (healthy n=10, sicca syndrome n=17, other rheumatic diseases 29) were studied. At first examination 54% of the pSS patients and none of the controls showed the characteristic pattern of multiple or confluent hypoechogenic rounded lesions typical for pSS, (p < 0.001). Patients with SS-typical US pattern had significantly higher ESSDAI score (8.6 vs. 3.3) and IgG levels (22.2 vs.14.9g/l) (both p<0.001), significantly more often a history of systemic disease (78% vs. 49%, p=0.003), autoantibodies to Ro and La (93% vs. 55%), RF (79% vs 40%) (both p<0.001) and GC-like structures in the salivary gland biopsy (44% vs. 16%, p=0.018). Swollen parotid glands and palpable purpura were seen significantly more often. Flow-cytometry revealed lower percentages of CD4+ T-cells, memory B-cells (both p<0.001) and a lower CD4+/CD8+ ratio (p=0.003). Trends were seen towards lower levels of complement factor 3 and 4, and increased percentage of naive B cells. In 30 individuals repeated SGUS was performed with a median 12 (range 2-23) months interval. Scores from the two investigations were highly correlated. Kappa: 0.54. Only 5 patients newly acquired the classical pSS pattern, mainly patients with short disease duration at baseline. Conclusions SGUS is a non-radiating bedside investigation with high specificity for pSS. Patients with these lesions have higher disease activity and more often other risk markers for lymphoma development. Given the fact that pSS usually is characterized by a stable disease state and not treated with potent medication, the high consensus between the repeated investigations signals high intra-observer reliability of the method. References Hocevar A et al. Ultrasonographic changes of major salivary glands in primary Sjogren’s syndrome. Diagnostic value of a novel scoring system. Rheumatology (Oxford) 2005;44:768-72. Theander E et al. Diagnostic utility and prognostic value of parotid gland ultrasonography in primary Sjögren’s Syndrome: The classical hypoechogenic pattern of parenchymal abnormality is highly specific, associated with higher disease activity and systemic disease. ARD 2012 June S 3 : 16,904 Disclosure of Interest None Declared