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Objective Calcinosis is a debilitating complication of systemic sclerosis (SSc) with no effective treatments. We sought to identify clinical correlations and to characterize complications and disability associated with calcinosis in a multi-center, international cohort of SSc patients. Methods We established a cohort of 568 consecutive SSc patients who fulfill 2013 revised ACR/EULAR criteria at 10 centers within North America, Australia, and Mexico. Calcinosis was defined as subcutaneous calcium deposition by imaging and/or physical examination, or a clear history of extruded calcium. All patients completed the Scleroderma Health Assessment Questionnaire Disability Index and Cochin Hand Functional Scale. Results 215 (38%) patients had calcinosis. In multivariable analysis, disease duration (OR=1.24, p = 0.029), digital ischemia (OR=1.8, p = 0.002) and Acro-osteolysis (OR=2.97, p = 0.008) were significantly associated with calcinosis. In the subset of patients with bone densitometry (n = 68), patients with calcinosis had significantly lower median T-scores than patients without (-2.2 vs. -1.7, p = 0.004). The most common location of calcinosis lesions was the hands (70%), particularly the thumbs (19%) with decreasing frequency moving to the fifth fingers (8%). The most common complications were tenderness (29% of patients) and spontaneous extrusion of calcinosis through the skin (20%), while infection was rare (2%). Disability and hand function were worse in patients with calcinosis, particularly if locations in addition to the fingers/thumbs were involved. Conclusions We confirmed a strong association between calcinosis and digital ischemia. Calcinosis in SSc patients most commonly affects the hands and is associated with a high burden of disability and hand dysfunction.

Background The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized. Methods We report our experience of patients who were evaluated by rheumatology after the development of a suspected rheumatic irAE following ICI treatment. Cases of rheumatic irAEs were included if active rheumatic signs or symptoms developed during or after ICI treatment and were confirmed by a treating rheumatologist. Results Twenty-nine patients were evaluated by rheumatology for suspected rheumatic irAEs. Eighteen patients had confirmed toxicity including inflammatory arthritis (n = 12) and PMR (n = 6). Twelve patients had de novo toxicity and six had a flare of a pre-existing rheumatic condition. The onset of de novo toxicity occurred late into treatment (median 38 weeks), while patients with pre-existing rheumatic disease flared soon after initiation of ICI treatment (median 4.6 weeks). Management often required systemic or intra-articular steroids, with initiation of disease modifying anti-rheumatic drug (DMARD) therapy in those unable to wean off steroids. Conclusion De novo rheumatic irAEs are generally delayed in onset after ICI initiation, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation. Effective management often requires systemic corticosteroids as well as DMARDs in a subset of patients. Future prospective studies are needed to accurately describe the incidence and spectrum of rheumatic irAEs and to identify the most effective management strategies.

Objective To determine the risk of venous thromboembolism (VTE) (pulmonary embolism [PE] and deep vein thrombosis [DVT]) in individuals with incident systemic sclerosis (SSc; scleroderma) in the general population. Methods Using a population database that includes all residents of British Columbia, Canada, we conducted a cohort study of all patients with incident SSc and up to 10 age-, sex-, and entry time–matched individuals from the general population. We compared incidence rates of PE, DVT, and VTE between the 2 groups according to SSc disease duration. We calculated hazard ratios (HRs), adjusting for confounders. Results Among 1,245 individuals with SSc (83% female, mean age 56 years), the incidence rates of PE, DVT, and VTE were 3.47, 3.48, and 6.56 per 1,000 person-years, respectively, whereas the corresponding rates were 0.78, 0.76, and 1.37 per 1,000 person-years among 12,670 non-SSc individuals. Compared with non-SSc individuals, the multivariable HRs among SSc patients were 3.73 (95% confidence interval [95% CI] 1.98–7.04), 2.96 (95% CI 1.54–5.69), and 3.47 (95% CI 2.14–5.64) for PE, DVT, and VTE, respectively. The age-, sex-, and entry time–matched HRs for PE, DVT, and VTE were highest during the first year after SSc diagnosis (32.77 [95% CI 6.60–162.75], 8.50 [95% CI 3.13–23.04], and 12.03 [95% CI 5.27–27.45], respectively). Conclusion These findings provide population-based evidence that SSc patients are at a substantially increased risk of VTE, especially within the first year after SSc diagnosis. Increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted in this patient population.

Background Dual lipid-lowering and anti-inflammatory properties of statins may lead to survival benefits in patients with rheumatoid arthritis (RA). However, data on this topic are limited, and the role of statins in RA remains unclear. Objectives To examine the association of statin use with overall mortality among patients with RA in a general population context. Methods We conducted an incident user cohort study with time-stratified propensity score matching using a UK general population database. The study population included individuals aged ≥20 years who had a diagnosis of RA and had used at least one disease-modifying antirheumatic drug (DMARD) between January 2000 and December 2012. To closely account for potential confounders, we compared propensity score matched cohorts of statin initiators and comparators (non-initiators) within 1-year cohort accrual blocks. Results 432 deaths occurred during follow-up (mean 4.51 years) of the 2943 statin initiators for an incidence rate of 32.6/1000 person-years (PY), while the 513 deaths among 2943 matched comparators resulted in an incidence rate of 40.6/1000 PY. Baseline characteristics were well-balanced across the two groups. Statin initiation was associated with a 21% lower risk of all-cause mortality (HR=0.79, 95% CI 0.68 to 0.91). When we defined RA by its diagnosis code alone (not requiring DMARD use), the corresponding HR was 0.81 (95% CI 0.74 to 0.90). Conclusions Statin initiation is associated with a lower risk of mortality among patients with RA. The magnitude of association is similar to that seen in previous randomised trials among the general population.

Systemic sclerosis (SSc) is a heterogeneous disease of unknown etiology and with limited effective therapies. It is characterized by autoimmunity, vasculopathy and fibrosis and is clinically manifested by multi-organ involvement. Interstitial lung disease (ILD) is a common complication of the disease and is associated with significant morbidity and mortality. The diagnosis of ILD hinges upon careful clinical evaluation as well as pulmonary function tests (PFTs) and high resolution computed tomography (HRCT). A number of pro-inflammatory and pro-fibrotic mediators are involved in the pathogenesis of SSc-ILD, with transforming growth factor-beta (TGF-β) playing a key role in the development of fibrosis. Despite recent advances in the understanding of the mechanisms of disease initiation and progression, effective therapeutic options are still limited. A number of experimental therapies are currently in early phase clinical trials and show promise.

Objectives Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. Methods We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. Results Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). Conclusion This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.

Background Rheumatoid arthritis (RA) is associated with an increased risk of mortality;[1] however, recent mortality trends in RA are largely unknown, particularly in the general population. Objectives To address this knowledge gap, we evaluated mortality trends among RA patients between Jan 1, 1999 and Dec 31, 2012 in a general population context. Methods Using The Health Improvement Network, an electronic medical record database representative of the UK general population, we identified individuals with incident cases of RA and up to 5 non-RA controls matched on sex, age, year of birth, and year of RA diagnosis, between 1999 and 2012 (i.e., ≥1 year before the end of our dataset to allow for follow-up). The RA cohort was then divided in two cohorts based on the year of RA diagnosis (i.e., 1999-2005 and 2006-2012) to evaluate changes in mortality. We calculated hazard ratios for death using a Cox-proportional hazards model and the rate differences using an additive hazard model, while additionally adjusting for potential confounders (i.e., number of GP visits, body mass index, smoking, alcohol and Charlson Comorbidity Index). Results The early cohort (1999-2005) RA patients had considerably higher mortality rates than the late cohort (2006-2012) (i.e., 23.8 vs. 15.7 cases per 1000 person-years), as compared with only a moderate improvement in the comparison cohorts between the two periods (14.1 to 11.1 cases per 1000 person-years). The corresponding absolute mortality rate differences were 9.7 (95% CI, 7.2-12.2) cases and 4.7 (95% CI, 2.9-6.4) cases per 1000 person-years (p for interaction Conclusions This general population-based study shows that survival of RA patients has improved over the past decade, suggesting that new treatments and improved management of complications and associated comorbidities may be providing substantial benefits. References Annals of the Rheumatic Diseases 2014 Jan;73(1):149-153. Disclosure of Interest None declared

Objective To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE. Methods We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment. Results We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects. Conclusions CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature.

Background Given their lipid-lowering and anti-inflammatory properties, statins may have dual cardioprotective [1] and anti-rheumatic benefits [2] in rheumatoid arthritis (RA). These effects are expected to confer survival benefits in RA patients, at least similar to those observed in the JUPITER trial [1] among otherwise healthy individuals with low LDL-cholesterol but with elevated hsCRP (i.e., a 20% reduction in overall mortality). However, no relevant data are available in the field. Objectives To address this knowledge gap, we evaluated the impact of statin initiation on the risk of mortality among RA patients in a general population context. Methods We conducted an incident user cohort study with time-stratified propensity score matching in a UK general population database. Our primary definition of RA required an RA diagnostic code with at least one use of a DMARD [3]. We compared statin initiators and non-initiators among patients with a new diagnosis of RA between January 2000 and December 2012. The outcome of interest was all-cause mortality. To closely account for confounding by indication and potential calendar-time effects, we employed propensity score-matched cohorts of statin initiators and non-initiators within 1-year cohort accrual blocks. Propensity scores (i.e., the predicted probability of statin initiation) were estimated using 50 variables, including RA duration, demographics, socio-economic status, body mass index, lifestyle factors, comorbidities, medication use, and healthcare utilization. We used Cox proportional hazard models to calculate hazard ratios for mortality. Results Of 2,943 statin initiators, 432 died during the follow up period (mean=4.51 years), whereas among 2,943 matched non-initiators, 513 died during the follow up period (mean = 4.29 years) (Table 1). This corresponds to incidence rates of 32.6/1000 person-years (PY) and 40.6/1000 PY in the statin initiator and comparator groups, respectively. The baseline characteristics were well-balanced in the two groups. Statin initiation was associated with a 21% reduction in all-cause mortality (HR 0.79, 95% CI 0.68-0.91) (Figure 1a). When we defined RA by its diagnosis code alone (not requiring DMARD use), the corresponding HR was 0.81 (95% CI 0.74-0.90). When we compared the unmatched cohorts to examine the effectiveness of our propensity score matching, the statin initiators (n=3,438) actually showed a 46% higher risk of mortality (HR 1.46, 95% CI 1.28-1.67) than non-initiators (n=3,438) due to confounding by indication (Figure 1b). Conclusions Findings from this general population study indicate that statin initiation is associated with a survival benefit among RA patients, and its magnitude is similar to that shown in the JUPITER trial among non-RA patients [1]. References The New England Journal of Medicine. 2008. 359(21):2195-2207. Lancet. 2004. 363(9426):2015-2021. Arthritis and Rheumatism. 2008. 59(9):1314-1321. Disclosure of Interest None declared