OBJECTIVES:This study aims to assess the risks of primary and second primary keratinocyte cancers (KCs) in patients with rheumatoid arthritis (RA) and in relation to treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs. METHODS:Nationwide cohort study of patients treated with Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitor (TNFi), or non-TNFi bDMARDs, using data from the Swedish Rheumatology Quality Register linked to other registers including the National Cancer Register, 2012 through 2023. Adjusted hazard ratios (HRs) were estimated via Cox regression using TNFi as reference. RESULTS:We identified 21,756 unique patients with RA. Based on 155 incident KC with JAKi, 458 with non-TNFi and 766 with TNFi, the HR for JAKi vs TNFi was 1.39 (1.16-1.68), corresponding to 1 extra KC case per every 244 patients per year. For non-TNFi vs TNFi, the HR was 0.96 (0.86-1.08). By subtype, the HR for JAKi vs TNFi was 1.41 (1.13-1.75) for basal cell carcinoma and 1.49 (1.09-2.05) for squamous cell carcinoma (SCC). For abatacept vs etanercept, the HR for SCC was 1.48 (1.11-1.97). The HR for a second primary KC was 1.31 (0.94-1.82) for JAKi and 0.94 (0.75-1.17) for non-TNFi bDMARD vs TNFi. CONCLUSIONS:Patients treated with JAKi have an elevated risk of KC compared with patients treated with TNFi. Although the class of non-TNFi bDMARDs is not associated with increased KC risk, we repeated a drug-specific signal of increased risk for SCC with abatacept.

Objectives To assess the risk of second primary cancer and death in patients who has a cancer diagnosis following idiopathic inflammatory myopathies (IIM). Methods Using nationwide Swedish healthcare and population registers, we identified 2,346 patients diagnosed with IIM ≥18 years of age between 1998 and 2024. Patients were followed for up to 27 years for first and second post-IIM primary cancers and death. Cumulative incidence function and incidence rate of second primary cancer and death were estimated. A flexible parametric multistate model was used to estimate transition probabilities to cancer and death. Furthermore, risk and prognostic factors for second primary cancer and subsequent death were assessed using multivariable models. Results Of 326 patients diagnosed with cancer at or after IIM diagnosis, 37 developed a second primary cancer during a mean follow-up of four years (maximum 19 years). The cumulative incidence of second primary cancer over the entire follow-up period was 22% (95% CI 14-33%) while the absolute risk within four years after a first post-IIM cancer was below 5%. Being male (hazard ratio, HR=3.2, 95% CI 1.6-6.5) and having a cancer history (HR=3.4, 95% CI 1.5-8.0) were significant risk factors of second primary cancers. The three-year all-cause mortality risk after a second primary cancer was 46% (95% CI 44%-70%). Patients with dermatomyositis had a markedly elevated mortality risk following a second primary cancer diagnosis compared to non-dermatomyositis subtypes (HR=3.77, 95% CI 1.46-9.75). Conclusion These findings provide new insight into the burden of subsequent cancers among IIM cancer survivors and highlight the need for close clinical monitoring for patients with dermatomyositis to reduce premature mortality.

Objectives To investigate if psoriatic arthritis (PsA) itself and if biological disease-modifying antirheumatic drugs (bDMARDs) used in PsA are associated with increased risks of nonmelanoma skin cancer (NMSC). Methods From nationwide health and clinical rheumatology registers in 4 Nordic countries, we identified patients with PsA who between 2010 and 2021 started a: (i) tumour necrosis factor inhibitor (TNFi), or (ii) non-TNFi bDMARD, or were (iii) b/targeted synthetic (ts)DMARD naïve. For Sweden and Denmark, we identified incident patients with PsA (2010-2021) and corresponding general population (GP) comparator subjects. Using ever-treated follow-up, incidence rates and adjusted hazards ratios (aHRs) with 95% CIs were calculated for NMSC overall, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), respectively. Results We identified 619 NMSCs among incident patients with PsA (n = 23,553). We observed 221 NMSCs in TNFi-treated (n = 9999), 34 NMSCs in non-TNFi bDMARD-treated (n = 2200), and 433 NMSCs in b/tsDMARD-naïve (n = 19,089) PsA. The aHR of NMSC for incident PsA vs GP was 1.20 (1.11-1.31). Pooled aHRs for NMSC overall were 1.24 (1.03-1.50) with TNFi and 1.11 (0.75-1.63) with non-TNFi bDMARDs vs b/tsDMARD-naïve PsA. Corresponding aHRs of BCC were 1.21 (0.93-1.58) for TNFi and 0.85 (0.42-1.69) for non-TNFi bDMARDs, whereas aHRs for SCC were 1.46 (0.84-2.56) and 2.37 (0.95-5.90). Conclusions Increased risks of NMSC (SCC in particular) were found in patients with PsA compared with the GP. Compared with b/tsDMARD-naïve PsA, TNFi was associated with an increased risk of NMSC overall, whereas a nonsignificantly increased risk of SCC was seen for non-TNFi bDMARDs. However, causality between bDMARD use and NMSC in PsA remains uncertain.

Objective This nationwide descriptive study examined temporal trends in adverse pregnancy outcomes (APOs) and treatments in systemic lupus erythematosus (SLE) pregnancies in Sweden over 2003 to 2022.Methods Using nationwide Swedish registers, we identified 1,417 pregnancies of women with prevalent SLE and delivery dates in 2003 to 2022 and matched them to 14,133 non-SLE pregnancies from the general population on maternal age, delivery year, and parity. We assessed proportions of preeclampsia, preterm delivery, and small for gestational age (SGA) birth over time. Antimalarial, glucocorticoid, and low-dose aspirin use were examined during 2007 to 2022. Binomial generalized linear models with an identity link quantified mean annual absolute change (expressed in percentage points [pp]) in APO and treatment proportions.Results Overall, SLE pregnancies had 9.1% preeclampsia, 14.7% preterm delivery, and 6.9% SGA births (2003-2022). These outcomes remained stable in the general population but decreased in SLE pregnancies (preeclampsia from 14.1% in 2003-2004 to 9.6% in 2021-2022, -0.11 pp/y; preterm delivery from 25.9% to 11.2%, -0.63 pp/y; and SGA birth from 10.6% to 7.0%, -0.22 pp/y). Declines were more pronounced in nulliparous versus parous SLE pregnancies. APOs modestly decreased over time in SLE pregnancies with antiphospholipid syndrome. Antimalarial use during pregnancy increased from 23.9% in 2007-2008 to 76.5% in 2021-2022 (+3.3 pp/y). Low-dose aspirin use during pregnancy rose from 39.8% to 85.6% (+3.7 pp/y), whereas glucocorticoid use slightly decreased from 43.2% to 40.1% (-0.7 pp/y).Conclusion APOs in SLE pregnancies have decreased over the past two decades, potentially reflecting improved treatment strategies, particularly increased use of antimalarials and low-dose aspirin.

BACKGROUND:Data on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and kidney cancer (KC) are conflicting. This study aimed to evaluate this association in the general population and in patients with extensive NSAID use: rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS:We conducted a nationwide register-based cohort study of the Swedish general population and among patients with RA or SpA, among whom NSAID use was around five times higher. In each of these cohorts, we assessed the incidence of KC 2010 through 2021 by NSAID exposure as defined by repeated prescriptions. We also evaluated KC mortality in individuals treated (vs. not) with NSAIDs, taking the cancer stage into account. Adjusted hazard ratios (HRs) were calculated through Cox regression, taking age, sex, educational level, comorbidities and family history of KC into account. RESULTS:Based on 751 incident cases of KC among 393,709 individuals in the general population (33% NSAID-exposed), the HR for NSAID-exposure was 1.32 (95% confidence interval [CI] 1.13-1.54), with the highest HRs during the first year of follow-up (HR thereafter 1.20). The corresponding cancer stage-adjusted HR for mortality from KC with NSAID-exposure was 1.26 (95%CI 0.87-1.82). In RA and SpA, the HRs for KC incidence with NSAID exposure were 0.83 (95%CI 0.58-1.18) and 1.60 (95%CI 0.78-3.29), respectively. CONCLUSIONS:We found up to a 30% increase in the overall incidence and mortality from KC with NSAID in the general population. This association was attenuated beyond the first year of follow-up and inconsistent in populations with much higher NSAID use.

OBJECTIVE:To assess risks of adverse pregnancy outcomes (APOs) in a contemporary cohort of women with systemic sclerosis (SSc) in relation to the timing of SSc diagnosis and by parity. METHODS:From the nationwide Swedish Medical Birth Register, we assembled pregnancies with births in women with SSc and in comparator women from the general population (1998-2021). We classified pregnancies according to the timing of SSc diagnosis at birth: post-SSc (after SSc diagnosis [n = 94]) and pre-SSc (zero to three years [n = 39] or more than three years [n = 839] before diagnosis of SSc). We used regression models estimating relative risks (RRs) and odds ratios of APOs with 95% confidence intervals (CIs) in post-SSc and pre-SSc pregnancies, respectively. RESULTS:For post-SSc pregnancies, RRs of preeclampsia (3.8, 95% CI 1.8-7.8), preterm birth (3.3; 95% CI 1.8-6.1), and cesarean delivery (2.5; 95% CI 1.8-3.5) were increased. By contrast, there were no indications of increased proportions of maternal or neonatal death or stillbirth. Stratifying on parity, risks were considerably higher among primiparous post-SSc women (preeclampsia RR 7.5, 95% CI 3.5-16.1; preterm birth RR 5.1, 95% CI 2.5-10.5). We also noted increased odds of APOs in pre-SSc pregnancies, with the highest estimates in the zero to three years' pre-SSc pregnancies. CONCLUSION:Contemporary women with SSc displayed markedly increased risks of several APOs after SSc diagnosis; the risks of some APOs were already increased before diagnosis, particularly within three years. Our findings suggest that both preclinical and overt SSc have a substantial impact on pregnancy outcomes, especially in the first pregnancy, highlighting the importance of specialized care and close monitoring.

Introduction Many women need to use medications during breastfeeding. Very few medications have been adequately monitored, tested and labelled with safety information for this use. Prednisolone is one of these drugs. We aim to conduct a multicentre low-intervention clinical trial to determine the concentration of prednisolone in plasma of breastfed infants of lactating women treated with prednisolone. In addition, we will measure the concentration in maternal plasma and breast milk and calculate the daily infant dose (DID) and relative infant dose (RID). Infant cortisol levels will be analysed as a measure of clinical effects in the infants.Methods and analysis The study will be conducted at departments of obstetrics and gynaecology and specialist maternity and paediatric outpatient clinics in Sweden. We aim to include 30 lactating women treated with prednisolone and their breastfed infants. Breast milk and blood will be collected merely to study the secretion of prednisolone into breast milk and transfer to the infant. Participants will be treated with prednisolone according to their physician’s prescription. Study visits take place when the infant is approximately 6–8 weeks old. Milk and blood sampling of the mother will be performed at 1 hour after drug intake, in conjunction with the infant being fed. Blood sampling of the infant will be performed 2 hours after the feed. Breast milk and plasma will be biobanked for future research. Recruitment was initiated in 2024 and is ongoing. Patient representatives from the Swedish Rheumatism Association were involved in the planning of the study, and the organisation is providing information about the study on their website.Ethics and dissemination The clinical trial was approved by the Swedish Medical Product Agency (Dnr. 5.1.1-2023-104170). The results will be published in peer-reviewed scientific journals and disseminated at scientific meetings and through patient organisations’ websites.Trial registration number The clinical trial protocol is available via the Clinical Trial Information System at the European Medicines Agency (No. 2023-508913-18-00). It is also registered and publicly accessible at the EU PAS Register (EUPAS 1000000059).

OBJECTIVE:To estimate risk and to identify risk factors for preterm birth in pregnant women with psoriatic arthritis (PsA) in relation to maternal characteristics, treatment and disease activity, both before and during pregnancy. METHODS:We linked clinical rheumatology registers to medical birth registers in Sweden, Denmark and Norway and identified PsA pregnancies and control pregnancies 2006-2021, matched 1:10 on age, parity, country and birth year. Adjusted ORs (aORs) for preterm birth in PsA pregnancies vs control pregnancies were calculated overall and stratified by maternal characteristics, antirheumatic treatment and disease load (9 months before and during pregnancy). RESULTS:We observed 54 preterm births among 688 PsA pregnancies (7.8%) versus 312 among 6880 control pregnancies (4.5%); aOR, 95% CI: 1.80, 1.29 to 2.51. The risk estimate was largely unaffected by parity, smoking and body mass index. PsA pregnancies exposed to a combination of biologic and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and/or glucocorticoids during pregnancy had a markedly increased risk of preterm birth compared with control pregnancies (4.44, 2.07 to 9.50), whereas exposure to biological DMARD (bDMARD) monotherapy (primarily tumour necrosis factor inhibitors) had not (0.73, 0.22 to 2.42). High disease load before pregnancy was associated with increased risk. The proportion of preterm birth was higher in those stopping bDMARD during the first trimester (21%) opposed to those continuing past the first trimester (10%) based on few events. CONCLUSION:We identified an 80% increased risk of preterm birth in PsA pregnancies compared with control pregnancies. Antirheumatic combination therapy during and high disease load before pregnancy constituted risk factors. Discontinuing bDMARD treatment in early pregnancy further increased the risk. Our findings support that a subgroup of PsA pregnancies should be considered high-risk pregnancies.

Background There is some evidence of a higher prevalence of coeliac disease (CD) among patients with SLE than in the general population. However, the prevalence estimates vary substantially.Objective To investigate the prevalence of CD among patients with SLE through systematic review and meta-analysis.Methods We performed searches in the databases of Medline, Embase, Cochrane and Web of Science Core Collection between 1 January 1990 and 9 July 2023. A total of 2053 publications were rendered in the searches, of which 68 were reviewed in full text and 14 included in the analyses. Primary analysis estimated the pooled prevalence of biopsy-verified CD in patients with SLE. In the secondary analysis, the prevalence of serological markers indicative of CD was investigated. The quality of studies was appraised using the Joanna Briggs Institute Critical Appraisal Tool. We conducted meta-regression analyses to investigate associations between the prevalence of CD in individuals with SLE and publication year, study population size, CD prevalence in the general population, proportion of females and quality assessment score.Results A total of 14 studies met the inclusion criteria, of which 11 were included in the primary analysis of biopsy-verified CD. Among 1238 patients with SLE, 14 had CD. The weighted pooled prevalence of CD was 0.7% (95% CI 0.0 to 1.8). The weighted pooled prevalence of CD serological markers in 1063 patients with SLE was 3.7% (95% CI 1.4 to 6.7). In meta-regression analyses, no associations between CD prevalence and study characteristics, demographics and quality assessment scores were found.Conclusions In this meta-analysis, we found a weighted pooled prevalence of biopsy-verified CD in patients with SLE comparable with the prevalence in the general population. Our findings do not support routine screening for CD in patients with SLE. However, individual screening could be considered in cases of clinical suspicion and additional risk factors for CD.PROSPERO registration number CRD42022339594.

Objectives To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).Methods This population-based cohort study utilized Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling >= 1 HCQ prescription during the first trimester. The outcome was infant MCM within 1 year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes and corticosteroids). Modified Poisson regression models with robust variance were used to estimate risk ratios (RR) and 95% CI.Results We included 1007 births (453 exposed) and 2500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed and unexposed groups were 3.6%, 3.7% and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6% and 4.3%, respectively. The adjusted RRs (95% CI) were 1.29 (0.65, 2.56) in the SLE cohort, 1.32 (0.56, 3.13) in the RA cohort and 1.30 (0.76, 2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings.Conclusion First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy. Graphical Abstract

Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear. To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death. We identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model. Of 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with cancer after IIM, the 5-year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without cancer after IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with first cancer after IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer-specific mortality. We observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients.

BackgroundPatients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear.ObjectivesTo explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death.MethodsWe identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model.ResultsOf 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with cancer after IIM, the 5-year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without cancer after IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with first cancer after IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer-specific mortality.ConclusionWe observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients. image

Objective Assess cancer risks with Janus kinase inhibitors (JAKi) versus biological disease-modifying antirheumatic drugs (bDMARDs) in clinical practice. Methods Cohort study of patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) initiating treatment with JAKi, tumour necrosis factor inhibitors (TNFi) or other (non-TNFi) bDMARDs 2016–2020 using prospectively collected data from the Swedish Rheumatology Quality Register linked to other registers including the Cancer Register. We estimated incidence rates, and HRs via Cox regression, for all cancers excluding non-melanoma skin cancer (NMSC), and for individual cancer types including NMSC. Results We identified 10 447 patients with RA and 4443 patients with PsA who initiated treatment with JAKi, a non-TNFi bDMARD or a TNFi. Median follow-up times in RA were 1.95, 2.83 and 2.49 years, respectively. In RA, based on 38 incident cancers other than NMSC with JAKi vs 213 with TNFi the overall HR was 0.94 (95% CI 0.65 to 1.38). Based on 59 vs 189 incident NMSC, the HR was 1.39 (95% CI 1.01 to 1.91). At 2 or more years since treatment start, the HR for NMSC was 2.12 (95% CI 1.15 to 3.89). In PsA, based on 5 vs 73 incident cancers other than NMSC, and 8 vs 73 incident NMSC, the corresponding HRs were 1.9 (95% CI 0.7 to 5.2) and 2.1 (95% CI 0.8 to 5.3). Conclusion In clinical practice, the short-term risk of cancer other than NMSC in individuals initiating treatment with JAKi is not higher than for TNFi, but we found evidence of increased risk for NMSC.

Background Familial associations can be indicators of shared genetic susceptibility between two diseases. Previous data on familial autoimmunity in patients with idiopathic inflammatory myopathies (IIM) are scarce and inconsistent. Objectives To investigate which autoimmune diseases (ADs) may share genetic susceptibility with IIM, we examined the familial associations between IIM and different ADs. Methods In this Swedish population-based family study, we assembled 7615 first-degree relatives (FDRs) of 1620 patients with IIM and 37,309 relatives of 7797 matched individuals without IIM. Via register linkages, we ascertained rheumatoid arthritis, other rheumatic inflammatory diseases (RIDs), multiple sclerosis, inflammatory bowel diseases (IBD), type 1 diabetes mellitus, autoimmune thyroid diseases (AITD), coeliac disease (CeD) and myasthenia gravis among the FDRs. We estimated the familial association between IIM and each AD using conditional logistic regression and performed subgroup analyses by kinship. Results Patients with IIM had significantly higher odds of having >= 1 FDR affected by other RIDs (adjusted odds ratio [aOR] = 1.40, 95% confidence interval [CI] 1.11-1.78) and greater odds of having >= 2 FDRs affected by CeD (aOR = 3.57, 95% CI 1.28-9.92) compared to the individuals without IIM. In the analyses of any FDR pairs, we observed familial associations for other RIDs (aOR = 1.34, 95% CI 1.14-1.56), IBD (aOR = 1.20, 95% CI 1.02-1.41), AITD (aOR = 1.10, 95% CI 1.02-1.19) and CeD (aOR = 1.37, 95% CI 1.08-1.74) while associations for other ADs were not statistically significant. Conclusion The observed familial associations may suggest that IIM shares genetic susceptibility with various ADs, information that may be useful for clinical counselling and guiding future genetic studies of IIM.

Objective To examine if idiopathic inflammatory myopathies (IIMs) share familial susceptibility with cancer, we estimated the familial co‐aggregation of these diseases. Methods This Swedish population‐based family study with data from national registers included 8,460 first‐degree relatives of patients with IIM and 41,127 relatives of matched individuals without IIM. We modeled the adjusted odds ratios (ORs) of familial co‐aggregation of IIM and cancer using conditional logistic regressions and adjusted for sex and birth year of index individuals and their first‐degree relatives. We examined the associations for cancer overall and stratified by several factors of interest. We also performed exploratory analyses for specific cancer types. Results We observed no statistically significant familial associations between IIM and cancer overall. However, there was a familial association in male relative pairs of patients with dermatomyositis (adjusted OR for familial association 1.39 [95% confidence interval (95% CI) 1.15–1.68]). The association remained statistically significant after controlling for multiple testing. Moreover, this finding was consistent between kinships. Familial co‐aggregation of IIM and cancer diagnosed before 50 years of age was only observed in offspring. In exploratory analyses, only the familial associations for myeloid malignancies (adjusted OR 2.27 [95% CI 1.43–3.60]) and liver cancer (adjusted OR 2.01 [95% CI 1.21–3.33]) in male relative pairs remained significant after controlling for multiple testing. Conclusion We found little evidence of shared familial susceptibility as a major pathologic mechanism contributing to the co‐occurrence of IIM and cancer overall. There could be subsets of patients and cancer types for which familial factors including genetics and shared environments are of more importance, but these findings need replication.

BACKGROUND:Evidence on the risks associated with pregnancy and childbirth in women with axial spondyloarthritis is scarce and conflicting, with more research needed to guide policy and clinical practice. We aimed to assess the risks of adverse pregnancy outcomes in a large cohort of women with axial spondyloarthritis, and to investigate how outcomes varied over time and in relation to anti-rheumatic treatment. METHODS:In this register-based cohort study, we included births in Sweden between April 1, 2007, and Dec 31, 2020, to women with axial spondyloarthritis and general population comparators, matched 1:10 on year of delivery, maternal age, and parity. Our main data source was the Medical Birth Register (MBR), which includes over 98% of births in Sweden and prospectively collects data on antenatal care, delivery, and foetal outcomes. The information in MBR was linked to other registers, including the National Patient Register, the Prescribed Drug Register, and registers with demographic data. Our main outcomes were the relative risks of adverse pregnancy outcomes, analysed using modified Poisson regression. We also studied how the frequency of certain adverse outcomes, as well as disease-modifying antirheumatic drug (DMARD) and non-steroidal anti-inflammatory drug treatments, changed over the study period by linear regression and loess plots. FINDINGS:Between April 1, 2007, and Dec 31, 2020, 1580 births in women with axial spondyloarthritis recorded in MBR fulfilled the inclusion criteria and were matched with 15 792 comparator births. Among the 1580 births in women with axial spondyloarthritis, we found increased risks of preterm birth (risk ratio 1·43, 95% CI 1·13-1·80), pre-eclampsia (1·44, 1·08-1·92), elective caesarean delivery (1·59, 1·37-1·84), and serious infant infection (1·29, 1·05-1·59) compared with births in general population comparators. The risks of preterm birth, infant infection, and caesarean delivery decreased by around 0·5 percentage points annually during the study period, while the use of tumour necrosis factor inhibitors during pregnancy increased. INTERPRETATION:In view of remaining concerns regarding safety of the use of biological DMARDs during pregnancy, we saw a reassuring trend in which pregnancy outcomes improved over time in the axial spondyloarthritis group, concurrent with increased use of biological DMARDs. If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes. FUNDING:Swedish Research Council and The Swedish Rheumatism Association.

Familial associations can be indicators of shared genetic susceptibility between two diseases. Previous data on familial autoimmunity in patients with idiopathic inflammatory myopathies (IIM) are scarce and inconsistent. To investigate which autoimmune diseases (ADs) may share genetic susceptibility with IIM, we examined the familial associations between IIM and different ADs. In this Swedish population-based family study, we assembled 7615 first-degree relatives (FDRs) of 1620 patients with IIM and 37,309 relatives of 7797 matched individuals without IIM. Via register linkages, we ascertained rheumatoid arthritis, other rheumatic inflammatory diseases (RIDs), multiple sclerosis, inflammatory bowel diseases (IBD), type 1 diabetes mellitus, autoimmune thyroid diseases (AITD), coeliac disease (CeD) and myasthenia gravis among the FDRs. We estimated the familial association between IIM and each AD using conditional logistic regression and performed subgroup analyses by kinship. Patients with IIM had significantly higher odds of having ≥1 FDR affected by other RIDs (adjusted odds ratio [aOR] = 1.40, 95% confidence interval [CI] 1.11–1.78) and greater odds of having ≥2 FDRs affected by CeD (aOR = 3.57, 95% CI 1.28–9.92) compared to the individuals without IIM. In the analyses of any FDR pairs, we observed familial associations for other RIDs (aOR = 1.34, 95% CI 1.14–1.56), IBD (aOR = 1.20, 95% CI 1.02–1.41), AITD (aOR = 1.10, 95% CI 1.02–1.19) and CeD (aOR = 1.37, 95% CI 1.08–1.74) while associations for other ADs were not statistically significant. The observed familial associations may suggest that IIM shares genetic susceptibility with various ADs, information that may be useful for clinical counselling and guiding future genetic studies of IIM.

Objectives To identify perinatal and early-life risk factors for ankylosing spondylitis (AS), controlling for family-shared confounding with a sibling comparison design.Methods In this nationwide, register-based case–control study, we identified 5612 AS cases from the Swedish National Patient Register, and matched them with 22 042 individuals without inflammatory arthritis from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of AS in relation to childhood infections and a broad range of perinatal factors including fetal growth. Significant associations were further tested in a sibling comparison analysis, including 3965 patients with AS and their 6070 siblings without a diagnosis of spondyloarthritis.Results We found no statistically significant associations between any studied fetal growth-related factor or other perinatal factors and the risk of developing AS. In contrast, having older siblings (adjusted OR 1.12; 95% CI 1.04 to 1.22 for one vs no older sibling) and history of a childhood tonsillectomy (adjusted OR 1.30; 95% CI 1.13 to 1.49) were associated with AS in the case–control analysis, results that also held in the sibling comparison. Serious childhood infection and multiple birth were significantly associated with AS in the case–control sample, but estimates were attenuated in the sibling comparison.Conclusions Having older siblings and a history of tonsillectomy in childhood were independently associated with development of AS, even after adjustment for family-shared factors in a sibling comparison analysis. This strengthens the hypothesis that childhood infections play a role in the aetiology of AS.

OBJECTIVE:To evaluate pregnancy outcomes in relation to antirheumatic treatment before and during pregnancy, as a proxy of disease severity in pregnant women with psoriatic arthritis (PsA), compared to those without PsA.METHODS:Our study focused on a Swedish nationwide registry-based cohort study that included 921 PsA pregnancies and 9,210 non-PsA pregnancies occurring between 2007 and 2017 (matched 1:10 based on maternal age, year of delivery, and parity). We estimated adjusted odds ratios (ORs) overall, with 95% confidence intervals (95% CIs), and stratified by presence, timing, and type of antirheumatic treatment. Adjustments were made for maternal body mass index, smoking, education level, and country of birth. The outcome of preterm birth was also stratified by parity.RESULTS:Pregnant women with PsA versus those without PsA were more obese, more often smokers, and more frequently had a diagnosis of pregestational hypertension and diabetes mellitus. Increased risks in PsA pregnancies versus non-PsA pregnancies were primarily preterm birth (adjusted OR 1.69 [95% CI 1.27-2.24]) and cesarean delivery (adjusted OR 1.77 [95% CI 1.43-2.20] for elective delivery, and adjusted OR 1.42 [95% CI 1.10-1.84] for emergency delivery). The risks differed according to the presence, timing, and type of antirheumatic treatment, with the most increased risk in PsA pregnancies (versus non-PsA) occurring with antirheumatic treatment during pregnancy (adjusted OR 2.30 [95% CI 1.49-3.56] for preterm birth). The corresponding adjusted OR for preterm birth in women with PsA who were exposed specifically to biologic treatment during pregnancy was 4.49 [95% CI 2.60-7.79]. Risk of preterm birth was primarily increased in first pregnancies.CONCLUSION:Compared to non-PsA pregnancies, risks of preterm birth and cesarean delivery were mostly increased in those exposed to antirheumatic treatment during pregnancy, especially biologic treatments. As parity influences the risk of preterm birth in women with PsA, special attention to first pregnancies is warranted. Women with PsA should receive individualized monitoring during pregnancy.