Impact of cancer on the mortality of patients with idiopathic inflammatory myopathies by flexible parametric multistate modelling.

BACKGROUND: Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear. OBJECTIVES: To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Familial autoimmunity in patients with idiopathic inflammatory myopathies.

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.

Survival in Swedish patients with systemic sclerosis: a nationwide population-based matched cohort study.

OBJECTIVES: To conduct the first-ever nationwide, population-based cohort study investigating survival patterns of all patients with incident SSc in Sweden compared with matched individuals from the Swedish general population. METHODS: We used the National Patient Register to identify patients with incident SSc diagnosed between 2004 and 2015 and the Total Population Register to identify comparators (1:5), matched on sex, birth year and residential area. We followed them until death, emigration or the end of 2016. Follow-up of the general population comparators started the same date as their matched patients were included. We estimated all-cause survival using the Kaplan-Meier method, crude mortality rates and hazard ratios (HRs) using flexible parametric models. RESULTS: We identified 1139 incident patients with SSc and 5613 matched comparators. The median follow-up was 5.0 years in patients with SSc and 6.0 years for their comparators. During follow-up, 268 deaths occurred in patients with SSc and 554 in their comparators. The 5-year survival was 79.8% and the 10-year survival was 67.7% among patients with SSc vs 92.9% and 84.8%, respectively, for the comparators (P < 0.0001). The mortality rate in patients with SSc was 42.1 per 1000 person-years and 15.8 per 1000 person-years in their comparators, corresponding to an HR of 3.7 (95% CI 2.9, 4.7) at the end of the first year of follow-up and 2.0 (95% CI 1.4, 2.8) at the end of the follow-up period. CONCLUSION: Despite advances in understanding the disease and in diagnostic methods over the past decades, survival is still severely impacted in Swedish patients diagnosed with SSc between 2004 and 2015.

ELISA, protein immunoprecipitation and line blot assays for anti-TIF1-gamma autoantibody detection in cancer-associated dermatomyositis.

OBJECTIVES: Anti-TIF1-gamma autoantibodies can be detected with immunoprecipitation (IP), line blot (LB) and ELISA. We compared assay performance in patients with DM and the potential of these assays to detect anti-TIF1-gamma positive cancer-associated DM (CADM). METHODS: We included sera from 131 patients with DM followed at Karolinska University Hospital, Stockholm, Sweden and 82 healthy controls. Serum samples taken at DM diagnosis were tested for anti-TIF1-gamma autoantibodies with IP, two ELISAs (in-house and commercial) and LB. Cancer diagnosis and dates were obtained from the Swedish national cancer register. CADM was defined as a malignancy that developed within 3 years of DM diagnosis. RESULTS: Anti-TIF1-gamma autoantibodies were detected in 19/101 (18.8%), 15/113 (13.2%), 34/131 (26%) and 45/131 (34.4%) of the patients with IP, LB, in-house and commercial ELISA, respectively. The anti-TIF1-gamma results from the in-house ELISA were confirmed with IP in 93 of 101 (92%) cases, κ = 0.76, with a commercial ELISA in 110 of 131 (84%) cases, κ = 0.63, and with LB in 101 of 113 (89.3%) cases, κ = 0.67. Anti-TIF1-gamma results with IP were confirmed with LB in 85 of 92 (92.4%) cases, κ = 0.73. For detecting CADM, the anti-TIF1-gamma in-house ELISA had a sensitivity of 58% and specificity of 86%, the commercial ELISA had a sensitivity of 63% and specificity of 82%, IP had a sensitivity of 52% and specificity of 92%, LB had a sensitivity of 40% and specificity of 96%. CONCLUSION: The two anti-TIF1-gamma ELISA assays had advantages both for autoantibody detection and to identify anti-TIF1-gamma-positive CADM.

Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study).

BACKGROUND: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited. METHODS: A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls. Co-allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co-allergy to pistachio or walnut were challenged to the respective nut. RESULTS: Forty-four of 50 OIT-treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9-17.7, p < 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co-allergic patients were cross-desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full-dose cashew OFC. CONCLUSIONS: Cashew OIT desensitizes most cashew-allergic patients and cross-desensitizes to pistachio. Safety is similar to OIT for other foods.

Familial aggregation and heritability: a nationwide family-based study of idiopathic inflammatory myopathies.

OBJECTIVES: The magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM. METHODS: This is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM. RESULTS: We included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings. CONCLUSIONS: IIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling.

Incidence and prevalence of systemic sclerosis globally: a comprehensive systematic review and meta-analysis.

OBJECTIVES: We aimed to conduct a systematic review and meta-analysis on the incidence and prevalence of SSc covering the entire literature. METHODS: This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of 2009. We conducted a systematic search in MEDLINE, Web of Science and Embase to identify articles reporting incidence and/or prevalence of SSc. Two authors conducted the search, reviewed articles for inclusion and extracted relevant data. We used random-effects models to estimate the pooled prevalence and incidence of SSc and performed subgroup analyses by sex, case definition and region to investigate heterogeneity. We explored the association between calendar period and reported estimates using meta-regression. RESULTS: Among 6983 unique records identified, we included 61 studies of prevalence and 39 studies of incidence in the systematic review. The overall pooled prevalence of SSc was 17.6 (95% CI 15.1, 20.5) per 100 000 and the overall pooled incidence rate of SSc was 1.4 (95% CI 1.1, 1.9) per 100 000 person-years. We observed significant regional variations in reported estimates; studies conducted in North America reported considerably higher estimates than other regions. The pooled incidence and prevalence in women were five times higher than in men. More recent studies reported higher estimates than older ones. CONCLUSION: In this comprehensive review of the incidence and prevalence of SSc across the world, there was large heterogeneity among estimates, which should be taken into consideration when interpreting the results.

Combinatorial advantage of Ses i 1-specific IgE and basophil activation for diagnosis of sesame food allergy.

BACKGROUND: The prevalence of sesame food allergy (SFA) is increasing worldwide with the potential of anaphylactic reactions upon exposure. Utility of specific component IgE testing as an alternative to the oral food challenge (OFC), the diagnostic standard, is being investigated. METHODS: Patients (n = 42) with suspected SFA completed an open OFC to sesame. Diagnostic testing included serum levels of Ses i 1-specific IgE, skin prick test with high-protein extract, and basophil reactivity (% induced CD63 expression) for each patient. The diagnostic utility of these tests was evaluated at a 95% sensitivity, with the outcome measure being the number of OFCs required. RESULTS: Twenty-seven patients (64%) were diagnosed with SFA. Ses i 1 IgE differed significantly between allergic and tolerant patients (p = .0001). ROC curve analysis for Ses i 1 IgE yielded an AUC of 0.88 ± 0.05. Levels of Ses i 1 IgE correlated to induced CD63+ expression on basophils (p = .0001). Ses i 1 IgE was not sufficiently robust as a single step for diagnosis. Used concurrently, BAT and Ses i 1 IgE yielded correct positive classifications for 25 of 27 sesame-allergic patients with two false positives (93% PPV). Both tests were negative in 5 non-allergic patients. Patients with divergent Ses i 1 IgE and BAT results required OFC (n = 10, 24% of patients). Alternatively, sequential use of BAT, ruling in SFA followed by Ses i 1 IgE diagnosing non-allergic patients, yielded a 89% PPV, with 19% requiring OFC. CONCLUSION: Ses i 1 IgE and BAT used together can decrease the need for OFC in most SFA patients. A prospective cohort trial is necessary to validate these results.

Pregnancy outcomes in women with idiopathic inflammatory myopathy, before and after diagnosis-a population-based study.

OBJECTIVES: To examine pregnancy outcomes among births to women with idiopathic inflammatory myopathy (IIM) in relation to time of IIM diagnosis using population-based data. METHODS: This study used Swedish nationwide registers to identify all singleton births that occurred between 1973 and 2016 among women diagnosed with IIM between 1998 and 2016 and among women unexposed to IIM. We classified births according to the IIM status of the mother at time of delivery: post-IIM (n = 68), 1-3 years pre-IIM (n = 23), >3 years pre-IIM (n = 710) and unexposed to IIM (n = 4101). Multivariate regression models were used to estimate relative risks of adverse pregnancy outcomes in post-IIM births and pre-IIM births separately, in comparison with their non-IIM comparators. RESULTS: We found that post-IIM births had increased risks of caesarean section [adjusted relative risk (aRR) = 1.98; 95% CI: 1.08, 3.64], preterm birth (aRR = 3.35; 95% CI: 1.28, 8.73) and low birth weight (aRR = 5.69; 95% CI: 1.84, 17.55) compared with non-IIM comparators. We also noticed higher frequencies of caesarean section and instrumental delivery in 1-3 years pre-IIM births than in the non-IIM comparators. CONCLUSION: Women who gave birth after IIM diagnosis had higher risks of caesarean section, preterm birth and low birth weight. These results further underline the importance of special care and close monitoring of women with IIM. Higher frequencies of caesarean section and instrumental delivery in pre-IIM births highlight the need for future research on the influence of subclinical features of IIM on pregnancy outcomes.

Anti-transcriptional intermediary factor 1 gamma antibodies in cancer-associated myositis: a longitudinal study.

OBJECTIVES: To investigate anti-TIF1-γ antibodies in longitudinally followed patients with myositis and cancer. METHODS: Serum levels of anti-TIF1-γ antibodies at different time-points in relation to myositis and cancer diagnosis were analysed by ELISA in 79 patients from a Swedish cohort with polymyositis (PM) and dermatomyositis (DM) and a Spanish cohort restricted to DM patients. Anti-TIF1-γ positive and negative patients were compared with Fisher's exact test, student t-tests and Wilcoxon test. RESULTS: Thirty-six patients (17 from cohort 1 and 19 from cohort 2) with myositis and cancer were anti-TIF1-γ antibody positive; all had DM. In 88% of anti-TIF1-γ positive patients, cancer was diagnosed within 3 years from DM diagnosis compared to 63% in anti-TIF1-γ negative. Four DM patients, anti-TIF1-γ positive at cancer diagnosis had positive serum samples even antedating cancer diagnosis up to five years. In cohort 1 the median (interquartile range) antibody level was higher, 2.13 au (1.82-2.15), in the seven patients who died <1 year after cancer diagnosis, compared to the seven that died >1 year after cancer diagnosis, 1.34 au (0.92-1.59), (p=0.004). Three patients were still alive and in remission from cancer and DM 14-16 years after cancer treatment of whom two became negative for anti-TIF1-γ antibodies. In the second cohort remission of cancer coincided with remission of DM and low or negative serum levels of autoantibodies. CONCLUSIONS: Anti-TIF1-γ antibodies may be detected before clinical symptoms of cancer and may disappear after successful treatment of cancer with remission of DM supporting DM being a paramalignant phenomenon.

Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome.

OBJECTIVES: To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. METHODS: By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996-2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations. RESULTS: We identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations. CONCLUSION: Siblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).

Efficacy and safety of rituximab in anti-synthetase antibody positive and negative subjects with idiopathic inflammatory myopathy: a registry-based study.

OBJECTIVE: Post-hoc analyses of the Rituximab in Myositis trial indicate that specific autoantibodies profiles may influence treatment response. We compared the efficacy and safety of rituximab in anti-synthetase antibody (ARS-ab) positive and negative patients. METHODS: Adult idiopathic inflammatory myopathy (IIM) subjects in the Swedish Rheumatology Quality Register who received ⩾ 1 cycle of rituximab were enrolled. Efficacy assessment was based on the International Myositis Assessment and Clinical Studies (IMACS) core set measures and the 2016 ACR/EULAR definition of improvement for PM and DM. Safety assessment included drug-related adverse event and death during study period. Comparisons were done within and between the ARS-ab defined groups before and after first and last cycles. Associations between selected clinical features and improvement after one rituximab cycle were assessed using logistic regression. RESULTS: Sixty-five subjects were included and 43 had a follow-up visit within 5-10 months. Seventy-eight percent of ARS-ab positive subjects had moderate/major ACR/EULAR improvement after one cycle compared with 50% in the ARS-ab negative group. After several cycles, 79% of the ARS-ab positive and 67% of the ARS-ab negative patients achieved moderate/major improvement. A significant glucocorticoid-sparing effect was only observed in the ARS-ab positive group (P = 0.001). The most frequent adverse events were infections. One ARS-ab positive and two ARS-ab negative patients died during follow-up period. CONCLUSION: Irrespectively of their autoantibody status, a majority of subjects treated with several rituximab cycles had moderate/major improvement. In addition, ARS-ab positive subjects experienced a significant glucocorticoid-sparing effect.

Mortality following new-onset Rheumatoid Arthritis: has modern Rheumatology had an impact?

OBJECTIVE: To investigate if, and when, patients diagnosed with rheumatoid arthritis (RA) in recent years are at increased risk of death. METHODS: Using an extensive register linkage, we designed a population-based nationwide cohort study in Sweden. Patients with new-onset RA from the Swedish Rheumatology Quality Register, and individually matched comparators from the general population were followed with respect to death, as captured by the total population register. RESULTS: 17 512 patients with new-onset RA between 1 January 1997 and 31 December 2014, and 78 847 matched general population comparator subjects were followed from RA diagnosis until death, emigration or 31 December 2015. There was a steady decrease in absolute mortality rates over calendar time, both in the RA cohort and in the general population. Although the relative risk of death in the RA cohort was not increased (HR=1.01, 95% CI 0.96 to 1.06), an excess mortality in the RA cohort was present 5 years after RA diagnosis (HR after 10 years since RA diagnosis=1.43 (95% CI 1.28 to 1.59)), across all calendar periods of RA diagnosis. Taking RA disease duration into account, there was no clear trend towards lower excess mortality for patients diagnosed more recently. CONCLUSIONS: Despite decreasing mortality rates, RA continues to be linked to an increased risk of death. Thus, despite advancements in RA management during recent years, increased efforts to prevent disease progression and comorbidity, from disease onset, are needed.

Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study.

Patients with idiopathic inflammatory myopathies (IIMs) suffer an increased burden of comorbidities, but data on mortality in recently diagnosed IIM are conflicting. Also, little is known when, if ever, in relation to IIM diagnosis, mortality is increased. METHODS: A population-based IIM cohort of patients diagnosed between 2002 and 2011 and general population comparators were identified using healthcare registers. They were linked to the cause of death register for follow-up. RESULTS: 224 (31%) of the 716 patients with IIM and 870 (12%) of the 7100 general population died during follow-up. This corresponded to a mortality rate of 60/1000 person-years in IIM and 20/1000 person-years in the general population. The cumulative mortality at 1 year after diagnosis was 9% in IIM and 1% in the general population, and increased in both IIM and the general population with time. The overall hazard ratio (HR) 95%CI of death comparing IIM with the general population was 3.7 (3.2 to 4.4). When we stratified on time since diagnosis, we noted an increase in mortality already within the first year of diagnosis compared with the general population, HR 9.6 (95% CI 6.9 to 13.5). This HR then plateaued around 2 after >10 years with the disease, although the estimates were not statistically significant. Malignancies, diseases of the circulatory and respiratory system were common causes of death. CONCLUSION: Mortality is increased in patients with contemporary IIM. The increased mortality was noted within a year of diagnosis, which calls for extra vigilance during the first year of IIM diagnosis.

Acute coronary syndrome in new-onset rheumatoid arthritis: a population-based nationwide cohort study of time trends in risks and excess risks.

BACKGROUND: Acute coronary syndrome (ACS) and other cardiovascular diseases are the main drivers of the increased morbidity and preterm mortality in rheumatoid arthritis (RA). ACS in RA has been linked to inflammation and RA severity. During recent years and with new therapeutic options and treat-to-target strategies, increasing efforts have been made to reach RA remission as soon as possible after diagnosis, and the average level of RA disease activity has declined. Whether this has resulted in declining excess risks for RA comorbidities remains unclear. METHODS: We performed a nationwide population-based cohort study of patients with new-onset RA from 1997 to 2014, and matched general population comparators. In the Swedish healthcare system, all residents have equal access to healthcare services. Healthcare is monitored using high-quality population-based registers that can be linked together. 15 744 patients with new-onset RA, identified from the Swedish Rheumatology Quality Register, and 70 899 general population comparator subjects were included. RESULTS: Seven hundred and seventy two patients with RA developed an ACS during 103 835 person-years of follow-up (crude incidence, 7.4 per 1000), corresponding to an overall HR versus the general population of 1.41 (95% CI 1.29 to 1.54). Whereas the ACS incidence declined over calendar time in both the RA and the general population cohort, the excess and the relative risks of ACS remained the same. CONCLUSIONS: Despite improved disease control in new-onset RA, the elevated risk of ACS in RA remains a concern.

Long-term outcomes and secondary prevention after acute coronary events in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of acute coronary syndrome (ACS) and suffer from poorer short-term outcomes after ACS. The aims of this study were to assess long-term outcomes in patients with RA with ACS compared with non-RA patients with ACS, and to investigate whether the use of secondary preventive drugs could explain any differences in ACS outcome. METHODS: We performed a cohort study based on 1135 patients with RA and 3184 non-RA patients who all developed an incident ACS between 2007 and 2010. We assessed 1-year and overall relative risks for ACS recurrence and mortality, as well as prescriptions of standard of care secondary preventive drugs. RESULTS: The risk of ACS recurrence, and of mortality, was increased in RA, both at 1 year after adjusting for baseline comorbidities (HR=1.30(95% CI 1.04 to 1.62) and 1.38(95% CI 1.20 to 1.59), respectively) and throughout the complete (mean 2 years) follow-up (HR=1.27(95% CI 1.06 to 1.52) and 1.50(95% CI 1.34 to 1.68), respectively). Among certain subgroups of ACS, there was a tendency of lower usage of statins, whereas there were no apparent differences in others. The increased rates of ACS recurrence and mortality remained in subgroup analyses of individuals whose prescription pattern indicated both adequate initiation and persistence to secondary preventive treatments. CONCLUSIONS: Patients with RA suffer from an increased risk of ACS recurrence and of death following ACS compared with general population, which in the present study could not readily be explained by differences in usage of secondary preventive drugs.

Infections and respiratory tract disease as risk factors for idiopathic inflammatory myopathies: a population-based case-control study.

OBJECTIVES: To investigate the association between infection or respiratory tract disease and future risk of developing idiopathic inflammatory myopathy (IIM). METHODS: A case-control study was performed using Swedish nationwide registers. Adults with newly diagnosed IIM were identified (2002-2011) from the National Patient Register (NPR) and the Swedish Rheumatology Register (n=957). Controls were matched by age, sex and place of residence (n=9476). Outpatient visits and hospitalisations preceding IIM diagnosis indicating infection or respiratory disease were identified from NPR. Conditional logistic regression models were used to calculate OR and 95% CI. Sensitivity analyses were performed by varying the exposure definition, adjusting for previous healthcare consumption and excluding individuals with connective tissue disease, IIM lung phenotype or IIM-associated cancer. RESULTS: Preceding infections were more common in IIM cases compared with controls (13% vs 9%) and were associated with an increased risk of IIM (OR 1.5, 95% CI 1.2 to 1.9). Gastrointestinal and respiratory tract infections were associated with an increased risk of IIM while cutaneous infections were not.Preceding respiratory tract disease was present in 10% of IIM cases and 4% of controls (OR 2.3, 95% CI 1.8 to 3.0). Both upper and lower respiratory tract diseases were associated with an increased risk of IIM.Variations in exposure and outcome definitions did not greatly affect the results. CONCLUSIONS: Infections and respiratory tract diseases are associated with an increased risk of IIM which suggests that the triggering of the immune system may take place outside the skeletal muscle.

Risk of diabetes mellitus associated with disease-modifying antirheumatic drugs and statins in rheumatoid arthritis.

OBJECTIVE: To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. METHODS: We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without baseline DM from 2000 through 2014. DM was determined by self-report or initiating DM medication. DMARDs were categorised into four mutually exclusive groups: (1) methotrexate monotherapy (reference); (2) any abatacept with or without synthetic DMARDs (3) any other DMARDs with methotrexate; (4) all other DMARDs without methotrexate; along with separate statin, glucocorticoid and hydroxychloroquine (yes/no) variables. Time-varying Cox proportional hazard models were used to adjust for age, sex, socioeconomic status, comorbidities, body mass index and RA severity measures. RESULTS: During a median (IQR) 4.6 (2.5-8.8) years of follow-up in 13 669 patients with RA, 1139 incident DM cases were observed. The standardised incidence ratio (95% CI) of DM in patients with RA (1.37, (1.29 to 1.45)) was increased compared with US adult population. Adjusted HR (95% CI) for DM were 0.67 (0.57 to 0.80) for hydroxychloroquine, 0.52 (0.31 to 0.89) for abatacept (compared with methotrexate monotherapy), 1.31 (1.15 to 1.49) for glucocorticoids and 1.56 (1.36 to 1.78) for statins. Other synthetic/biological DMARDs were not associated with any risk change. Concomitant use of glucocorticoids did not alter DM risk reduction with hydroxychloroquine (HR 0.69 (0.51 to 0.93)). CONCLUSIONS: In RA, incidence of DM is increased. Hydroxychloroquine and abatacept were associated with decreased risk of DM, and glucocorticoids and statins with increased risk.

Incidence and prevalence of idiopathic inflammatory myopathies in Sweden: a nationwide population-based study.

Objectives: To estimate the incidence rate and prevalence of idiopathic inflammatory myopathies (IIMs) in Sweden across clinical subgroups, age, sex, educational level and place of residence and to assess the robustness of register-based case definitions. Methods: IIM was identified from the Swedish National Patient Register and the Swedish Rheumatology Quality Register. The base case definition required ⩾2 visits indicating IIM (first ever with a consecutive visit within 1-12 months for incident cases) and the robustness was tested by applying a more liberal and a stricter definition. Results: Using the base case definition, 558 incident IIM patients were identified between 2007 and 2011. The incidence was estimated to 11 (13 for women and 9.7 for men) per 1 000 000 person years and was stable across case definitions. Incidence increased with age and peaked at the 50-79 years age groups. No differences were observed between different levels of education and place of residence. We identified 1267 IIM patients on 1 January 2012 corresponding to a prevalence of 14 per 100 000. Conclusion: We present nationwide register-based incidence and prevalence estimates for IIM, robust across three different case definitions. In contrast to many other reports, we did not find incidence by age to be bimodal and we found no explanation of incidence variation across education and residency. These register-based case definitions can be included in future population-based studies to better understand disease aetiology, risk factors and comorbidities.