Background: Non-melanoma skin cancer (NMSC) comprises one third of all malignancies diagnosed worldwide each year. NMSC primarily consists of two subtypes: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Current literature suggests that psoriasis is associated with an increased risk of NMSC, but studies on the risk of NMSC in patients with psoriatic arthritis (PsA) remain sparse.[1] Under particular scrutiny is the impact of treatment with biologic disease-modifying anti-rheumatic drugs (bDMARDs)—including tumour necrosis factor inhibitors (TNFi)—on NMSC risk, which in patients with PsA is largely unknown. Objectives: To explore the risk of NMSC overall, BCC, and SCC in patients with PsA treated with TNFi or other bDMARDs compared with bDMARD-naïve PsA patients in a real-world clinical setting. Methods: We performed an observational cohort study using nationwide health care and clinical rheumatology registers (SRQ, DANBIO) in Sweden and Denmark. With a study period from 1 January 2010 to 31 December 2021, using SRQ and DANBIO we identified all patients with PsA above 18 years of age and without any prior cancer diagnosis who were: 1) bDMARD naïve, 2) a TNFi initiator, or 3) an initiator of other bDMARDs. Follow-up started on the date of the first registered visit in SRQ/DANBIO, first ever start of TNFi, and first ever start of any other bDMARD, respectively. Each patient was followed for NMSC overall as well as for BCC and SCC outcomes separately. We employed an ‘ever-treated’ approach, although follow-up in the bDMARD naïve group was stopped upon start of TNFi or start of any other bDMARD. This allowed for each unique patient to contribute person years (PY) of follow-up and outcomes to several treatment groups. Country-specific hazard ratios (HR) with 95% confidence intervals (95%CI) for NMSC overall, BCC, and SCC were calculated using Cox regression with attained age as time scale, hereby comparing both TNFi and other bDMARDs with bDMARD naïve PsA patients as the reference group. All Cox models were adjusted for calendar period, sex, and PsA disease duration. We used a fixed-effects meta-analysis to estimate pooled HRs and 95%CIs. Results: For Sweden and Denmark combined, we identified 17 354 bDMARD-naïve, 8458 TNFi-treated, and 2012 other bDMARD-treated patients with PsA, contributing 87 161, 44 317, and 7598 PY of follow-up, respectively. A total of 651 NMSC overall, 505 BCC, and 87 SCC occurred during follow-up. In the pooled analyses (see Figure 1), we found a HR of 1.25 (95%CI 1.04 to 1.50) for NMSC in TNFi treated compared with bDMARD naïve patients with PsA. The HR for NMSC in those treated with other bDMARDs was 1.19 (95%CI 0.82 to 1.72). Specifically looking at BCC, the TNFi group showed a HR of 1.23 (95%CI 0.99 to 1.52) compared with bDMARD naïve, while the HR of BCC with other bDMARDs was 0.98 (95%CI 0.62 to 1.57). The HR for SCC was numerically increased in the TNFi group with a HR of 1.56 (95%CI 0.91 to 2.65) compared with bDMARD naïve, and albeit based on few events in the SCC group (n=8) we also observed an increased HR for SCC in PsA patients treated with other bDMARDs: HR 2.95 (95%CI 1.26 to 6.91). Conclusion: In this Swedish-Danish cohort study on patients with PsA, treatment with TNFi was associated with a small increased risk of NMSC and with non-significant numeric risk increases for both BCC and SCC compared with bDMARD naïve. Treatment with other bDMARDs was not associated with an increased risk of BCC, whereas we found a threefold increase in risk for SCC compared with bDMARD naive. Although based on few events and the fact that we cannot rule out the presence of channeling bias and surveillance bias, this signal of increased SCC risk in PsA patients treated with other bDMARDs calls for further investigations. REFERENCES: [1] Vaengebjerg S, et al. Prevalence, Incidence, and Risk of Cancer in Patients With Psoriasis and Psoriatic Arthritis: A Systematic Review and Meta-analysis. JAMA Dermatol. 2020. Acknowledgements: We thank the Swedish (SRQ) and Danish (DANBIO) clinical rheumatology registers for allowing us to use their clinical data. Further, we would also like to acknowledge NordForsk. Disclosure of Interests: Rasmus Westermann: None declared, Bénédicte Delcoigne is partly employed by the ARTIS Swedish national safety monitoring system for which grants from Abbvie, Astra-Zeneca, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB have been received., René Lindholm Cordtz is employed by IQVIA outside of the present study, has received a consultancy fee from Galapagos, Johan Askling has agreements between Karolinska Institutet (with JA as PI) and the listed entities, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS): Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, Lene Dreyer has received research grants (paid to her institution) from BMS and Abbvie outside the current manuscript. She is member of the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies, Karin Hellgren is employed at the Swedish Medical Products Agency of Sweden, the views expressed in this abstract are the personal views of the authors and not necessarily the views of the of the Government agency.

Background Hydroxychloroquine (HCQ) is currently recommended for all pregnant women with systemic lupus erythematosus (SLE) if tolerated. Some studies have reported an increased risk of malformations associated with HCQ, but others find no increased risk. Objectives To assess the risk of major congenital malformations (MCM) associated with exposure to HCQ during the 1st trimester in the offspring of women with SLE. Methods We conducted a population-based cohort study of pregnancies with a singleton birth from 2006 to 2020 among women with prevalent SLE in Sweden. Pregnancies were identified from the Medical Birth Register (MBR). Prevalent SLE was defined as having at least two ICD-coded visits in the National Patient Register before pregnancy, with at least one with an SLE specialist. The exposure was defined as filling at least one HCQ prescription during the 1st trimester (Prescribed Drug Register). The unexposed births were required to not have any HCQ dispensations from three months preconception to the end of the 1st trimester. The outcome was any ICD code for MCM in the offspring assessed at birth listed in the MBR, defined according to the European Surveillance of Congenital Anomalies classification. Inverse probability of treatment weighting (IPTW) using propensity score was applied to adjust for confounding. We included maternal characteristics, comorbidities (e.g., diabetes, other autoimmune diseases), and medication use (e.g., corticosteroids, other disease-modifying anti-rheumatic drugs) in the propensity score model as a priori variables. Risk ratios and 95% confidence intervals (RR 95%CI) were estimated using modified Poisson regression models in the weighted population with robust variance estimation. Results The study population comprised 407 exposed births and 520 unexposed births. The mothers’ mean age at delivery was 32 (standard deviation ± 5). Overall, there were 21 births with at least one MCM, corresponding to an overall risk of 2.3%. The most common type of MCM was ventricular septal defect (n = 6). The unadjusted risks of MCM among the exposed and unexposed were 2.7% and 1.9%, respectively (unadjusted RR 1.42, 95%CI 0.60-3.28). The IPTW-adjusted population achieved a good balance across patient characteristics. The IPTW-adjusted RR was 1.59 (95%CI 0.67-3.75). The adjusted risk difference was 0.01 (95%CI -0.01-0.03). In a sensitivity analysis in which the exposure was defined as having at least one HCQ dispensation from three months preconception to the end of the 1st trimester, the IPTW-adjusted RR was 1.56 (95%CI 0.69-3.54). We could not examine different categories of HCQ daily dose due to very few events in each category. Conclusion In this birth cohort, our findings show an increased, but not statistically significant, risk of MCM at birth among births born to women with SLE exposed to HCQ during the 1st trimester compared to those without HCQ exposure. Our findings should be interpreted considering the lack of data on early pregnancy termination or loss induced by MCM. Future studies are warranted to investigate this association further and should utilize a longer follow-up for MCM ascertainment (i.e., within one year of birth). For managing SLE during pregnancy, the benefits of HCQ may still outweigh the risks. References [1]Diav-Citrin O, Blyakhman S, Shechtman S, Ornoy A. Pregnancy outcome following in utero exposure to hydroxychloroquine: a prospective comparative observational study. Reprod Toxicol Elmsford N. 2013 Aug;39:58–62. [2]Huybrechts KF, Bateman BT, Zhu Y, Straub L, Mogun H, Kim SC, et al. Hydroxychloroquine early in pregnancy and risk of birth defects. Am J Obstet Gynecol. 2021 Mar;224(3):290.e1-290.e22. [3]Howley MM, Werler MM, Fisher SC, Van Zutphen AR, Carmichael SL, Broussard CS, et al. Maternal exposure to hydroxychloroquine and birth defects. Birth Defects Res. 2021 Oct 15;113(17):1245–56. Acknowledgements: NIL. Disclosure of Interests Ngoc V. Nguyen: None declared, Elisabet Svenungsson Shareholder of: AstraZeneca and Pfizer, Speakers bureau: Janssen, Grant/research support from: Grant support from Merck, Annica Dominicus Shareholder of: AstraZeneca, Consultant of: AstraZeneca, Employee of: AstraZeneca, Karin Hellgren: None declared, Julia Simard: None declared, Elizabeth Arkema: None declared.

Background A growing body of evidence suggests that there are associations between perinatal factors or early life exposures and later development of chronic inflammatory diseases. For ankylosing spondylitis (AS), previous studies have found increased risks associated with birth order and childhood respiratory tract infections, while breast-feeding and childhood appendicitis have been found protective. Objectives To identify early life risk factors for AS, with focus on perinatal characteristics and childhood infections. Methods People with AS from the Swedish National Patient Register, born 1973-2004, were matched 1:5 on age, sex, and place of residence to general population controls. Conditional logistic regression was used to compare odds ratios for AS in relation to potential risk factors identified in the Medical Birth Register and the National Patient Register. Results People with AS (n=5427) had significantly more hospitalizations for infections before age 16 compared to controls (n=21523), and had more often gone through a tonsillectomy (table 1). People with AS were also more likely to be born in the winter months, and to have an older sibling, while having a sibling overall (older or younger) resulted in an odds ratio for AS of 1.01 (0.93-1.11). No association was seen with factors such as maternal age, Caesarean delivery, or a 1 SD change in weight for gestational age (table 1). Odds ratios for AS associated with being born small or large for gestational age (>2 SD below or above sex-specific mean weight) was 1.10 (0.93-1.30) and 0.89 (0.74-1.08), respectively. In line with previous data, childhood appendectomy was associated with an odds ratio <1, but the estimate did not reach statistical significance. Conclusion Childhood exposures related to infections seem to play a role in later development of AS, while factors generally associated with foetal growth do not. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Perinatal factors and childhood infections in people with AS and general population controls, with odds ratios from conditional logistic regressionAS cases*(n=5472)Controls*(n=21523)OR (95% CI)Adj. OR† (95% CI)Maternal age, years27.4 (5.0)27.4 (5.1)1.00 (0.99-1.00)1.00 (0.99-1.00)Smoking, early pregnancy669 (12.2)2683 (12.5)1.00 (0.90-1.11)1.01 (0.90-1.13)Maternal BMI22.6 (3.3)22.8 (3.6)1.00 (0.98-1.01)1.00 (0.98-1.01)Weight for gestational age, SDs-0.10 (1.12)-0.10 (1.10)1.01 (0.98-1.03)1.01 (0.98-1.04)Caesarean delivery604 (11.0)2253 (10.5)1.07 (0.97-1.18)1.07 (0.97-1.18)No. of older siblings02110 (38.6)8897 (41.3)RefRef12121 (38.8)7872 (36.6)1.14 (1.06-1.22)1.17 (1.09-1.26)≥21241 (22.7)4754 (22.1)1.11 (1.03-1.20)1.19 (1.09-1.31)Season of birthDec-Feb1361 (24.9)5039 (23.4)RefRefMarch-May1573 (28.7)5985 (27.8)0.97 (0.89-1.05)0.97 (0.89-1.05)June-Aug1349 (24.7)5461 (25.4)0.91 (0.84-0.99)0.91 (0.84-0.99)Sep-Nov1189 (21.7)5038 (23.4)0.87 (0.79-0.95)0.87 (0.80-0.95)Serious infection‡1362 (25.0)4898 (22.8)1.12 (1.05-1.21)1.12 (1.05-1.21)Tonsillectomy‡272 (5.0)840 (3.9)1.28 (1.11-1.48)1.28 (1.11-1.48)Appendectomy‡123 (2.3)566 (2.6)0.86 (0.70-1.05)0.86 (0.70-1.05)* Numbers are n (%) or mean (SD). † Adjusted for maternal age, maternal BMI, maternal smoking, parents born in Nordic country, maternal disposable income, maternal educational level, maternal inflammatory disease (hospitalization for spondyloarthritis, inflammatory bowel disease, or psoriasis), sex of child, and multiple birth. ‡ Before age 16, with people diagnosed with AS before age 16 excluded.

Background Pregnancy is an important issue for young women with inflammatory systemic disease and pose a clinical challenge. Objectives The aim of this case report is to underline the challenges to correctly diagnose pregnancy complications versus disease flare in pregnant women with overlap syndrome. Methods Clinical information collected from the patient’s journal. Results A 26 years old woman was referred to Karolinska University Hospital because of Raynaud’s phenomenon, sclerodactyly, skin rash, palate ulcerations and recurrent finger ulcerations with necrosis, infections and self-amputation of distal phalanges. Interstitial lung disease was confirmed by high resolution CT and a restrictive pattern on lung function tests. Immunological analyses detected autoantibodies against Scl-70, ribosomal-P, SS-A, SS-B, Ku, as well as dsDNA with immunofluorescence technique with varying titers over the years. Complement activation, anemia and lymphopenia were also present. The patient experienced muscle weakness and peripheral muscle MRI and muscle biopsy confirmed myositis. During follow-up she developed pericardial effusion and myocarditis. The patient was diagnosed with overlap syndrome with clinical and serological features of systemic sclerosis, SLE and myositis. The immunosuppressive treatment over the disease course comprised hydroxychloroquine, methotrexate, azathioprine, rituximab and low dose prednisolone. Later, treatment was switched to mycophenolate mofetil because of flares on the previous regimens. For the digital ulcers, she was treated with nifedipine, sildenafil and iloprost infusions. Despite medical advice on pregnancy risks during active disease, the patient stopped medication with mycophenolate at the age of 35 years and became pregnant. Enalapril, spironolactone and sildenafil were discontinued and she was referred to the specialist maternity care. The pregnancy evolved without complications until week 18 when the blood pressure (BP) began to rise. In trying to avoid alpha blockers, because of recent finger ulcerations, nitrates and hydralazine were started without sufficient effect on the BP. Soon thereafter, she also developed marked trombocytopenia and hemolytic anemia. The titers of dsDNA antibodies were higher compared to the status before pregnancy and the creatinine and proBNP started to rise. Urine analysis revealed proteinuria and granular casts. Pre-eclampsia was suspected, though SLE flare with active nephritis, hemolysis and trombocytopenia could not be ruled out. Tacrolimus, intravenous immunoglobulin and methylprednisolone were started, as well as labetalol and diuretics. Plasmapheresis was applied twice. The BP remained uncontrolled and kidney function was deteriorating; therefore hemodialysis was started. Since the foetal growth was impaired and the patient’s clinical status was not improving, decision was made to stop the pregnancy. The medical abortion with vaginal birth proceeded without complications and minimal hemorrhage. Since hypertension and hemolysis continued post-abortion despite several antihypertensive drugs and the patient developed lung edema, renal crisis was suspected and the patient was started on enalapril. BP, and later on the renal function, improved slowly. Two weeks postpartum dialysis was no longer needed. Renal biopsy revealed thrombotic microangiopathy without signs of nephritis. Conclusion We described a patient with overlap syndrome who developed serious pregnancy complications that ended up with pregnancy termination in week 20. This case illustrates the difficulty in differential diagnostics of preeclampsia-induced hypertension with renal and hematological changes versus active SLE and the importance of keeping in mind that renal crisis may complicate the clinical picture in SLE/ scleroderma patients. Also, this case underscores the significance of low disease activity when starting a pregnancy and that every effort should be made for shared decision making. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Objective To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept.Methods This is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001-2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications.Results 33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively.Conclusion The cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events.

Background An increased risk of adverse pregnancy and neonatal outcomes has been reported for pregnancies in women with several rheumatic diseases including rheumatoid arthritis and psoriatic arthritis. In spondyloarthritis (SpA), findings have not been uniform, with some studies reporting increased risks of Cesarean delivery, preterm birth, infants born small-for-gestational-age (SGA), and gestational diabetes- and hypertension, while others have failed to identify any significant differences between women with SpA and general population control women. Most studies reporting no differences have either been small or lacked an appropriate comparison group [1]. Objectives To assess the risk of adverse maternal and infant pregnancy outcomes in women with SpA compared to the general population. Methods In this nationwide register-based study, we included singleton births between April 2007 and December 2019 in women diagnosed with ankylosing spondylitis (AS; ICD-10 codes M45 or M08.1) or undifferentiated SpA (uSpA; ICD-10 codes M46.8 or M46.9). This was performed through linkage between the National Patient Register and the Medical Birth Register. Each birth was matched on birth year, maternal age, and parity to ten comparator births in women free from chronic inflammatory arthritis at time of birth. Relative risks (RR) of adverse outcomes were estimated by Poisson regression, adjusting for maternal country of birth, BMI, smoking in early pregnancy, educational level, and disposable income in the year before pregnancy. Results Women with SpA (n=1394) were found to be at increased risk of several adverse outcomes compared to general population comparators (n=13932), as displayed in the Figure 1. Women with SpA had an increased risk of gestational diabetes (adjusted RR 1.88 [95% CI 1.10; 2.56]), elective and emergency Cesarean delivery (adjusted RR 1.54 [95% CI 1.32; 1.79] and 1.23 [95% CI 1.02; 1.48], respectively), and moderately preterm birth (adjusted RR 1.52 [95% CI 1.18; 1.97]). An association was seen with both spontaneous and medically indicated preterm birth, but the increase was only significant for spontaneous preterm birth. The risk estimate for preeclampsia was also increased, but failed to reach significance (adjusted RR 1.32 [95% CI 0.96; 1.81]). Infants to mothers with SpA were not more likely to be born SGA, but there was a slightly increased risk estimate of infection during their first year of life (adjusted RR 1.23 [95% CI 0.98; 1.53]). Figure 1. Number of events of adverse pregnancy outcomes among a nationwide cohort of births (n=1394) in Swedish women with SpA and comparator births (n=13932, matched 1:10 on birth year, maternal age, and parity). Relative risks from Poisson regression, adjusted for maternal country of birth, BMI, smoking in early pregnancy, educational level, and disposable income in the year before pregnancy. Conclusion While most pregnancies in women with SpA are uneventful, there is an increased risk for a number of adverse pregnancy outcomes. The increased risks for both emergency Cesarean delivery and spontaneous preterm birth suggest that these differences are not only driven by a different management of SpA pregnancies. References [1]Mokbel A, Lawson DO, Farrokhyar F. Pregnancy outcomes in women with ankylosing spondylitis: a scoping literature and methodological review. Clinical Rheumatology 2021;40(9):3465-80. Disclosure of Interests None declared

Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006-18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56-2.35)] and SGA [1.93 (1.45-2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP >= 4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52-7.55) for PTB and 3.90 (1.46-10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94-4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66-2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment.

Objective: To determine whether a family history of spondyloarthritis (SpA) is associated with clinical presentation at the start of tumour necrosis factor inhibitor (TNFi) treatment, or predictive of TNFi drug survival and treatment response in patients with SpA. Method: Family history of SpA in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated SpA (uSpA) from the Swedish Rheumatology Quality register starting a TNFi as their first biologic in 2006-2018 was assessed through national registers. Clinical characteristics at treatment start were compared by family history status. We used Cox regression to estimate hazard ratios for drug discontinuation, and analysed treatment response at 3 and 12 months with linear regression. Multiple imputation was used to address missing data. Results: We included 9608 patients. Patients with family history had an earlier age at onset and longer disease duration at TNFi treatment start, but did not differ regarding disease activity and presence of SpA manifestations. Hazard ratios for drug discontinuation were 1.08 [95% confidence interval (CI) 0.89-1.31] for AS patients with a family history of AS, 1.02 (95% CI 0.89-1.18) for PsA patients with a family history of PsA, and 1.11 (95% CI 0.85-1.45) for uSpA patients with a family history of uSpA, after adjusting for demographic, socioeconomic, and SpA-related factors. Treatment response at 3 and 12 months was similar between groups. Conclusion: Family history of SpA was not found to be associated with clinical presentation at the start of TNFi treatment, nor was it associated with drug survival or treatment response in SpA patients starting a first TNFi.

Background: Spondyloarthritis (SpA) is known to have high familial aggregation, with a positive family history of SpA being a strong risk factor for disease development, in particular for ankylosing spondylitis (AS). Despite this well-known characteristic of the disease, whether family history is associated with disease prognosis and treatment outcome has been much less studied. Patient characteristics predicting response to tumour necrosis factor alpha inhibitors (TNFi) in SpA include age, sex and high disease activity, but whether family history is predictive of TNFi treatment outcomes remains unclear. Objectives: To assess if a family history of psoriatic arthritis (PsA), AS, or SpA in general is associated with a different drug survival and treatment response to TNFi in patients with AS and PsA. Methods: Patients diagnosed with AS (N=1688) or PsA (N=3216) starting their first TNFi treatment between January 2006 and December 2017 were identified in the Swedish Rheumatology Quality Register (SRQ). Disease activity measures were extracted from SRQ at treatment start and at 3 and 12 months of treatment. Data on demographics and comorbidities were available through linkage to other national registries. Multiple imputation was applied to address missing data. Family history was defined as having at least one first-degree relative diagnosed with AS, PsA or any form of SpA in the National Patient Register at start of first TNFi. Analyses were made for AS and PsA index patients separately. Kaplan-Meier plots were used to compare drug survival, and hazard ratios for drug discontinuation were estimated with Cox regression adjusting for age, sex, disease duration and baseline disease activity. The change in disease activity from baseline to 3 months of treatment, and the proportion of patients remaining on treatment at 12 months and reaching low disease activity (LDA) with BASDAI (for AS) and DAS28-CRP (for PsA), were analysed in linear regression adjusting for age, sex, disease duration and baseline disease activity. Results: A positive family history of AS was found in 14% of AS patients, and 12% of PsA patients had a family history of PsA. Characteristics such as age, sex and baseline disease activity were similar in AS patients with and without a family history of AS. Among PsA patients, those with a family history of PsA were to a larger extent female, with lower CRP but longer disease duration. No significant differences were seen in drug survival among patients with and without a family history of their respective disease (Figure 1), with hazard ratios for drug discontinuation of 1.03 (95% CI 0.84 to 1.27) in AS patients and 1.08 (95% CI 0.94 to 1.25) in PsA patients. Using family history of any form of SpA as exposure did not change this conclusion. The changes in disease activity at 3 months of treatment compared to baseline were similar between groups. At 12 months, 55.2% of AS patients with a family history were still on treatment and had a BASDAI corresponding to LDA, compared to 56.4% of AS patients without a family history. Among PsA patients, 38.7% of patients with a family history had reached DAS28-CRP LDA, compared to 42.6% for those without a family history. For both AS and PsA, these differences were non-significant. Conclusion: While family history of SpA is a strong predictor of disease development, family history was not found to affect neither TNFi drug survival nor treatment response in patients with AS and PsA in this register-based study. Figure 1. Survival plots for time to TNFi discontinuation in patients diagnosed with AS and PsA respectively, by family history status Disclosure of Interests: Matilda Morin: None declared, Karin Hellgren Speakers bureau: KH has received speakers fee from Abbvie and UCB Nordic., Ulf Lindström: None declared, Thomas Frisell: None declared

ObjectiveStudies on pregnancy outcomes in psoriatic arthritis (PsA) are scarce and typically of small size. Available studies have reported conflicting results. The aim of this study was to describe maternal and infant pregnancy outcomes among women with PsA compared with women without PsA.DesignNationwide cohort study.SettingNationwide Swedish registers.PopulationA total of 41 485 singleton pregnancies in 1997–2014, of which 541 pregnancies were identified with PsA exposure and 40 944 pregnancies were unexposed.MethodsBy linkage of national health and population register data, we obtained information on individual pregnancies and compared outcomes among pregnancies with PsA and non‐PsA pregnancies. Relative risks were estimated by odds ratios (ORs) with 95% CIs using a generalised linear regression model with generalised estimating equations. Adjustments were made for maternal factors and calendar year of birth.Main outcome measuresMaternal and infant pregnancy outcomes.ResultsPregnancies to women with PsA had increased risks of preterm birth (adjusted OR 1.63; 95% CI 1.17–2.28), elective and emergency caesarean deliveries (adjusted OR 1.47; 95% CI 1.10–1.97 and adjusted OR 1.43; 95% CI 1.08–1.88, respectively) compared with non‐PsA pregnancies. No increased risks were observed for pre‐eclampsia, stillbirth or other infant outcomes apart from preterm birth.ConclusionThe majority of women with PsA have uneventful pregnancies with respect to adverse outcomes. In the present study, we found increased risks of preterm birth and caesarean delivery compared with non‐PsA pregnancies.Tweetable abstractWomen with psoriatic arthritis have uneventful pregnancies but are at increased risk of preterm birth and caesarean delivery.

OBJECTIVE:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes.METHODS:We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression.RESULTS:Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population.CONCLUSION:The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.

Aim: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. Methods: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). Results: The mean (SD) VMI score was 87 (+/- 12) in preterm children compared to 98 (+/- 11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. Conclusion: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

Background Active perinatal care increases the survival of extremely preterm infants but there are concerns that improved survival might increase the rate of disabled survivors. Objective To determine neurodevelopmental outcome at 6.5 years of age in extremely preterm children (EPT, <27 weeks) in a Swedish National cohort. Design/methods Poulation-based prospective cohort of all EPT children born in Sweden from April 1, 2004, to March 31, 2007. Survivors were assessed and compared with a term-born control group. Of 707 live-born infants, 69% survived to 6.5 years. Intellectual ability was measured with WISC- lV and results were related to the mean and SD of the controls. Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments. Results At a median age of 78 months, 445 of 494 eligible EPT children (90%) were assed (59 by chart review). The rates of cerebral palsy, moderate visual impairment, blindness and deafness were 9.2%, 5.2%, 2.0% and 0.7%, respectively vs 0.0%, 0.5%, 0% and 0%, respectively among 370 controls. 364 EPT children and 369 controls were formally tested with WISC-lV. Intellectual impairment < -2SD but >-3SD, and < -3SD was 9% and 19%, respectively vs 1.9% and 0%, respectively among controls. In 445 EPT children either formally assessed or by chart review, the rates of moderate and severe neurodevelopmental disabilities were 19% and 11%, respectively compared with 2.4% and 0%, respectively among control children. Conclusion Disability rates are comparable to similar studies that report lower survival rates.

Background Although family history of arthritis-related diseases is routinely collected as part of the work-up for rheumatoid arthritis (RA) in clinical practice, the interpretation of such information is often difficult since the relative importance of a family history of different arthritic and inflammatory diseases - beyond the established familial association of RA itself - is little known. Further, recent studies suggest that seropositive and seronegative RA have unique as well as shared genetic risk factors. However, with the exception of the HLA region, little is known about which genes or pathways are different between the two disease subsets. Objectives To assess the difference in predictive value of a family history of arthritis-related conditions for seropositive and seronegative RA, incidentally exploring the possible genetic difference of these disease subsets. Methods Register-based nested case-control study in the Swedish total population. RA was ascertained through the nationwide Patient register and the Swedish Rheumatology Register. First degree relatives were ascertained through the Swedish Multi-Generation Register. Autoimmune and arthritis-related diseases in relatives were assessed through the Patient register. Familial risks where calculated using conditional logistic regression with robust standard errors. Results Family history of seropositive RA was the strongest predictor of RA in the proband, regardless of serostatus. Statistically significant familial co-aggregation with RA was found for every arthritis-related disease under study, but risk increases varied widely (Table). With the exception of family history of RA itself, the difference in familial co-aggregation was very small for seropositive and seronegative RA. When combinations of family histories were examined, no arthritis-related disease added information beyond that provided by a family history of RA. Conclusions Seropositive and seronegative RA does not appear to differ much in the genetic risk factors that are shared with other arthritis-related diseases. Although a family history of (either of) several non-RA arthritis-related diseases is predictive of RA, the impact of others (e.g., osteoarthritis, unspecified athralgia) is negligible. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1720

Objective. Data on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern.Methods. Through the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi-exposed and TNFi-naive patients were compared.Results. For AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5-1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9-1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0-3.1). The numbers and incidence of lymphoma were not materially different in TNFi-exposed versus TNFi-naive AS and PsA patients, although the numbers of lymphomas were small.Conclusion. In contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.

Background Lymphoma risk in RA remains a concern, in particular the long-term risks with biological therapies. Objectives To extend assessments of relative risks, and of distribution of subtypes, of malignant lymphomas in patients with RA starting biological therapies Methods Data from the Swedish Biologics Register (ARTIS) were cross-linked with nation-wide population-based registers: the Patient Register, the Cancer Register, and the Total Population Register. Incidences of a first malignant lymphoma in patients starting a first anti-TNF therapy 1998 through 2010 (n=10,998) within a nation-wide cohort of patients with RA (n=42,230, censored at first start of anti-TNF therapy), and in a matched general population referent cohort (n=170,649) were compared using Cox’ regression (hazard ratios (HR)), taking age, sex, calendar time, selected co-morbidities, and family history of lymphoma into account. Patients were considered at risk since start of first anti-TNF therapy. HRs were assessed overall and per age and accumulated time of active anti-TNF therapy. Following histopathological review, the distribution of lymphoma subtypes was compared to previously reported distributions of biologics-naive RA-lymphomas 1964-1995 from our group (1) and to the distribution in general lymphoma patients ( National Swedish Lymphoma Register 2000-2006). Results Whereas both anti-TNF treated (45 lymphomas/56,493 person-years) and anti-TNF naive RA patients (185 lymphomas/197,056 person-years) were at increased risk compared to the general population (407 lymphomas/873,326 person-years), HR=2.2 (95% CI 1.6-2.9) and HR=1.9 (95%CI 1.6-2.3), respectively, the incidence of lymphoma following start of anti-TNF therapy was not higher than in anti-TNF naive RA, HR=1.1 (95%CI 0.8-1.6, Table). There was no obvious trend in HRs with accumulated time on active anti-TNF therapy, nor any appreciable difference in HRs across attained age during follow-up. The overall distribution of B-cell, T-cell and Hodgkin lymphoma was similar among anti-TNF treated RA, anti-TNF naive RA, and the general population lymphoma patients. Diffuse large B-cell lymphoma was numerically more frequent in anti-TNF treated RA (34%) than in general lymphoma patients (24%), but was lower than in biologics-naive RA from the pre-biologic era (48%). Of all anti-TNF treated lymphomas, 75 % had been treated with only one biologic. Conclusions In this study, the already increased lymphoma risk in patients with RA does not seem to increase further following anti-TNF therapy, at least not following up to 5-10 years of active treatment, nor did we find any treatment-related excess risk in younger or older adults. The distribution of lymphoma subtypes was not markedly different from that in general lymphoma patients. References Baecklund et al, Arthritis Rheum, 2006 Disclosure of Interest None Declared