Malignancy as a comorbidity in rheumatic diseases.

Patients with systemic autoimmune rheumatic diseases, particularly RA, SLE, SS and idiopathic inflammatory myopathies, are at increased risk of developing malignancies. Cancer occurrence adds to the disease burden in these patients, adversely affecting quality of life and life expectancy. This risk is related to the pathobiology of the underlying rheumatic disease including the inflammatory burden, immunological defects, and personal and environmental exposure such as smoking and some viral infections. Immunomodulatory therapies, especially chemotherapeutic agents, are also associated with an increased risk of cancer in these conditions. The decision to use immunomodulating therapies in patients with rheumatic disease must take into account the disease severity, expectations for disease control, comorbidities and host and environmental risk factors for cancer. Effective screening and monitoring strategies are important in reducing the risk of cancer in these patients

Cardiovascular co-morbidity in rheumatic diseases

Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed

Changes and sex differences in patient reported outcomes in rheumatoid factor positive RA-results from a community based study.

Patient reported outcomes (PROs) are important measures in rheumatoid arthritis (RA). A register of patients with RA from all rheumatology care providers in Malmö, Sweden, was established in 1997 and has been continually updated. This register includes virtually all the RA patients in the area. The aim of this study was to analyse PROs in surveys of this population conducted between 1997 and 2009, and to assess differences in treatment and outcome in male and female patients

Rate of comorbidities in giant cell arteritis : A population-based study

Objective. To compare the rate of occurrence of comorbidities, including severe infections, in a population-based cohort of patients with biopsy-proven giant cell arteritis (GCA) with a reference population in Southern Sweden. Methods. The study included a population-based cohort of biopsy-proven GCA cases diagnosed between 1998 and 2010 from the Skane region in Southern Sweden (population: 1.2 million). For each patient, 4 reference subjects were identified from the general population and matched for age, sex, area of residence, and date of diagnosis of GCA. Using the Skane Healthcare Register, comorbidities and severe infections (requiring hospitalization) diagnosed after GCA onset were identified. The rate of the first occurrence of each comorbidity was the result of dividing the number of subjects with a given comorbidity by the person-years of followup. The rate ratio (RR; GCA:reference population) was also calculated. Results. There were 768 patients (571 women) with GCA and 3066 reference persons included in the study. The RR were significantly elevated for osteoporosis (2.81, 95% CI 2.33-3.37), followed by venous thromboembolic diseases (2.36, 95% CI 1.61-3.40), severe infections (1.85, 95% CI 1.57-2.18), thyroid diseases (1.55, 95% CI 1.25-1.91), cerebrovascular accidents (1.40, 95% CI 1.12-1.74), and diabetes mellitus (1.29, 95% CI 1.05-1.56). The RR for ischemic heart disease was elevated, but did not reach statistical significance (1.20, 95% CI 1.00-1.44). Conclusion. Patients with GCA have higher rates of selected comorbidities, including severe infections, compared with a reference population. Several of these comorbidities may be related to treatment with glucocorticosteroids, emphasizing the unmet need to find alternative treatments for GCA

Second malignancies after multiple myeloma: from 1960s to 2010s.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Based on small numbers, recent reports from 3 randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after multiple myeloma has been known for over 4 decades. Most prior studies have been restricted because of small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biologic mechanisms of AML/MDS after multiple myeloma are unknown, treatment-related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was found among 5652 patients with IgG/IgA (but not IgM) monoclonal gammopathy of undetermined significance, supporting a role for disease-related factors. Furthermore, there is evidence to suggest that polymorphisms in germline genes may contribute to a person's susceptibility to subsequent cancers, whereas the potential influence of environmental and behavioral factors remains poorly understood. This review discusses current knowledge regarding second malignancies after multiple myeloma and gives future directions for efforts designed to characterize underlying biologic mechanisms, with the goal to maximize survival and minimize the risk for second malignancies for individual patients.National Cancer Institute of the National Institutes of Healt

Decrease in the incidence of total hip arthroplasties in patients with rheumatoid arthritis - results from a well defined population in south Sweden

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.INTRODUCTION: One aim of modern pharmacologic treatment in rheumatoid arthritis (RA) is to prevent joint destruction and reduce the need for surgery. Our purpose was to investigate secular trends in the incidence of primary total hip and knee arthroplasties in a well defined sample of patients with RA. METHODS: Prevalent cases with RA in 1997 and incident cases from 1997 to 2007 in a community based register in Malmö, south Sweden, were included. Based on a structured review of the medical records, patients were classified according to the 1987 ACR criteria for RA. This cohort was linked to the Swedish Hip Arthroplasty Register (through December 2006) and the Swedish Knee Arthroplasty Register (through October 2007). Patients with a registered total hip or knee arthroplasty before 1997 or before RA diagnosis were excluded. Incidence rates for the period of introduction of TNF inhibitors (1998 to 2001) were compared to the period when biologics were part of the established treatment for severe RA (2002 to 2006/2007). RESULTS: In the cohort (n = 2,164; 71% women) a primary hip arthroplasty was registered for 115 patients and a primary knee arthroplasty for 82 patients. The incidence of primary total hip arthroplasties decreased from the period 1998 to 2001 (12.6/1,000 person-years (pyr)) to 2002 to 2006 (6.6/1,000 pyr) (rate ratio (RR) 0.52; 95% confidence interval (CI) 0.35 to 0.76). There was a trend towards an increase of primary knee arthroplasties (incidence 4.8/1,000 pyr vs. 6.8/1,000 pyr; RR 1.43; 95% CI 0.89 to 2.31). CONCLUSIONS: Our investigation shows a significant decrease in the incidence of total hip arthroplasties in patients with RA after 2001. Possible explanations include a positive effect on joint damage from more aggressive pharmacological treatment.The Swedish Research Council Lund University Crafoord Foundation Swedish Rheumatism Associatio

History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesMultiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.Swedish Blodcancerfonden Swedish Cancer Society Stockholm County Council Karolinska Institutet Karolinska Institutet Foundations University of Iceland Icelandic Centre for Research (RANNIS) Landspitali University Hospita

EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy:A prospective observational study of patients registered in the south Swedish SSATG registry

Objectives Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-To-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. Materials and methods All RA patients registered in a regional database as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from 1st of January 2006 through 31st of December 2012, were included. Patients were followed from initiation of the first dose of bDMARD monotherapy treatment until withdrawal from treatment, loss of follow-up or 31st of December 2012. Descriptive statistics for utility (EQ-5D-3L), effectiveness, and drug survival of bDMARD monotherapy were calculated. Results During the study period, a total of 554 patients were registered in SSATG as initiating bDMARD monotherapy. Most of the patients were women (81%), with a mean age of 57 years. The average disease duration was more than 12 years, and on average the patients had previously been treated with approximately four different csDMARDs. Fifty-five percent of the patients were initiating their first bDMARD, 26% their second, and 19% their third or more. At baseline the average EQ-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences between type of bDMARD (p = 0.49). The mean change in EQ-5D-3L ranged from 0.11 (rituximab and infliximab) to 0.42 (tocilizumab). Although the changes were numerically different, no distinct pattern favored any particular bDMARD for EQ-5D-3L (p = 0.49) or other clinical outcomes. Overall, DAS28 defined remission and low disease activity were achieved in 20% and 43% of patients, respectively. Drug survival rates were statistically significantly different between bDMARDs (p = 0.01), with the highest rates observed for rituximab, followed by etanercept. After failing first course of anti-TNF, patients switching to another mode of action had significantly higher drug survival than those switching to a second course of anti-TNF therapy (p = 0.02). Conclusions Utility (EQ-5D-3L) increased after 6 months of all bDMARD treatments in monotherapy, indicating improvement of patients' quality of life. After failure of anti-TNF treatment in monotherapy, switching to another mode of action may be associated with better drug survival than starting a second TNF-inhibitor