Disease burden and treatment sequence of polymyositis and dermatomyositis patients in Japan: a real-world evidence study.

INTRODUCTION/OBJECTIVES: Since new consensus on polymyositis (PM) and dermatomyositis (DM) were released in Japan, an updated evidence on treatment landscape and PM/DM burden was essential. This study evaluates treatment burden and overall treatment cost of PM/DM-related inpatient and outpatient visits, treatments, and procedures/patient/year. METHOD: This retrospective, observational study analyzed insurance claims from Japan Medical Data Center (JMDC) database. Patients with at least one PM/DM diagnosis/one dispensation of treatment between 1 January 2009 and 31 December 2019 were enrolled. Patient characteristics, treatment patterns and sequence, treatment choices, healthcare resource utilization (HCRU), and related costs were assessed. Chi-square test and linear regression model were used to assess impact of patient characteristics on treatment choice. RESULTS: Patients (836/4,961) receiving a relevant treatment were analyzed. Heart disease (35%), interstitial lung disease (27%), and diabetes mellitus (26%) were frequently identified as comorbidities. Concomitant dispensation of immunosuppressants and systemic steroids was largely found in first and second line of treatment (LoT) while systemic steroids remained as single dominant treatment across all LoTs. HCRU was very low for inpatient visits (0.68 [1.43]) or rehabilitation (4.74 [14.57]). The mean (SD) number of inpatient visits decreased from first (1.23 [2.32]) to third year (0.11 [0.54]). Total mean (SD) healthcare cost per patients per year was ¥ 3,815,912 (7,412,241), with overall drug dispensation compounding to 80% of total cost. CONCLUSIONS: High concomitant immunosuppressant and systemic steroid prescriptions in first LoT recommend early optimal treatment to manage PM/DM. Although inpatient costs are low, outpatient dispensation costs increase overall economic burden.

Inpatient burden of juvenile dermatomyositis among children in the United States.

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare autoimmune disease that causes significant morbidity and quality of life impairment. Little is known about the inpatient burden of JDM in the US. Our goal was to determine the prevalence and risk factors for hospitalization with juvenile dermatomyositis and assess inpatient burden of JDM. METHODS: Data on 14,401,668 pediatric hospitalizations from the 2002-2012 Nationwide Inpatient Sample (NIS) was analyzed. ICD-9-CM coding was used to identify hospitalizations with a diagnosis of JDM. RESULTS: There were 909 and 495 weighted admissions with a primary or secondary diagnosis of JDM, respectively. In multivariable logistic regression models with stepwise selection, female sex (logistic regression; adjusted odds ratio [95% confidence interval]) (2.22 [2.05-2.42]), non-winter season (fall: 1.18[1.06-1.33]; spring (1.13 [1.01-1.27]; summer (1.53 [1.37-1.71]), non-Medicaid administered government insurance coverage (2.59 [2.26-2.97]), and multiple chronic conditions (2-5: 1.41[1.30-1.54]; 6+: 1.24[1.00-1.52]) were all associated with higher rates of hospitalization for JDM. The weighted total length of stay (LOS) and inflation-adjusted cost of care for patients with a primary inpatient diagnosis of JDM was 19,159 days and $49,339,995 with geometric means [95% CI] of 2.50 [2.27-2.76] days and $7350 [$6228-$8674], respectively. Costs of hospitalization in primary JDM and length of stay and cost in secondary JDM were significantly higher compared to those without JDM. Notably, race/ethnicity was associated with increased LOS (log-linear regression; adjusted beta [95% confidence interval]) (Hispanic: 0.28 [0.14-0.41]; other non-white: 0.59 [0.31-0.86]) and cost of care (Hispanic: 0.30 [0.05-0.55]). CONCLUSION: JDM contributes to both increased length of hospitalization and inpatient cost of care. Non-Medicaid government insurance was associated with higher rates of hospitalization for JDM while Hispanic and other non-white racial/ethnic groups demonstrated increased LOS and cost of care.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Predictors of Hospitalization, Length of Stay, and Cost of Care Among Adults With Dermatomyositis in the United States.

OBJECTIVE: To determine the prevalence and risk factors for hospitalization with dermatomyositis and assess inpatient burden of dermatomyositis. METHODS: Data on 72,651,487 hospitalizations from the 2002-2012 Nationwide Inpatient Sample, a 20% stratified sample of all acute-care hospitalizations in the US, were analyzed. International Classification of Diseases, Ninth Revision, Clinical Modification coding was used to identify hospitalizations with a diagnosis of dermatomyositis. RESULTS: There were 9,687 and 43,188 weighted admissions with a primary or secondary diagnosis of dermatomyositis, respectively. In multivariable logistic regression models with stepwise selection, female sex (logistic regression: adjusted odds ratio 2.05 [95% confidence interval (95% CI) 1.80, 2.34]), nonwhite race (African American: 1.68 [1.57, 1.79]; Hispanic: 2.38 [2.22, 2.55]; Asian: 1.54 [1.32, 1.81]; and multiracial/other: 1.65 [1.45, 1.88]), and multiple chronic conditions (2-5: 2.39 [2.20, 2.60] and ≥6: 2.80 [2.56, 3.07]) were all associated with higher rates of hospitalization for dermatomyositis. The weighted total length of stay (LOS) and inflation-adjusted cost of care for patients with a primary inpatient diagnosis of dermatomyositis was 80,686 days and $168,076,970, with geometric means of 5.38 (95% CI 5.08, 5.71) and $11,682 (95% CI $11,013, $12,392), respectively. LOS and costs of hospitalization were significantly higher in patients with dermatomyositis compared to those without. Notably, race/ethnicity was associated with increased LOS (log-linear regression: adjusted ß [95% CI] for African American: 0.14 [0.04, 0.25] and Asian: 0.38 [0.22, 0.55]) and cost of care (Asian: 0.51 [0.36, 0.67]). CONCLUSION: There is a significant and increasing inpatient burden for dermatomyositis in the US. There appear to be racial differences, as nonwhites have higher prevalence of admission, increased LOS, and cost of care.

Incidence and prevalence of polymyositis and dermatomyositis in a health management organization in Buenos Aires.

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are infrequent diseases. Data on incidence and prevalence are scarce and conflicting. There are no such data in Latin America and in Argentina in particular. OBJECTIVES: We undertook to examine the incidence and prevalence of PM/DM in the prepaid health maintenance organization (HMO) of our hospital, in the city of Buenos Aires. METHODS: Members of the HMO between January 1999 and June 2009 were identified from medical records of patients followed up by us at the HMO. Incident cases and prevalence were calculated at the end of the period. RESULTS: During the study period, 146,747 persons contributed a total of 937,902.6 person-years (mean age was 46.6 [SD, 18.4] years, and 59% were female). Ten incident cases were detected, 7 women and 3 men with a global incidence rate (IR) of 1.07 per 100,000 person-years (95% confidence interval [CI], 0.5-1.84). Three subjects had DM with an IR of 0.32 per 100,000 person-years (95% CI, 0.1-0.99), and 7 had PM with an IR of 0.75 per 100,000 person-years (95% CI, 0.35-0.16). On June 1, 2009, 17 prevalent cases were detected, with a mean age of 48.9 (SD, 17.7) years; 76% were female, representing a prevalence of 17.4 per 100,000 persons (95% CI, 10.1-27.8). Among the 17 patients with idiopathic inflammatory myopathy, 10 patients had DM, with a prevalence of 10.22 per 100,000 persons (95% CI, 4.9-18.8), and 7 had PM (prevalence, 7.2 per 100,000 persons [95% CI, 2.9-14.7]). CONCLUSIONS: It is difficult to compare studies from different populations and using different ascertainment techniques. These first data from Latin America are in general agreement with many studies.

The Myositis Activities Profile -- initial validation for assessment of polymyositis/dermatomyositis in the USA.

OBJECTIVE: To evaluate some measurement properties of the Myositis Activities Profile (MAP) in adult patients with polymyositis (PM) and dermatomyositis (DM) in the United States. METHODS: To assess content validity, patients with PM/DM rated difficulty and importance of items of the MAP using a visual analog scale (VAS), range 0-10. For construct validity, consecutive patients with PM/DM performed the 6-item core set for disease activity including the manual muscle test (MMT) and the Health Assessment Questionnaire (HAQ), the Functional Index-2 (FI-2; muscle endurance), and the MAP plus disease effect on well-being on a VAS. Item fit within subscales was analyzed by Cronbach's alpha. Patients with stable disease activity filled out the MAP again 1 week later. RESULTS: The median combined difficulty and importance, 0-10, of the 31 items was 5.00 (range 2.10-5.95). One item was added, giving a 32-item MAP. Correlations between the median of subscales/single items of the MAP and the HAQ and disease effect on well-being were r(s) = 0.69 and r(s) = 0.68, respectively, with lower correlations to the MMT (r(s) = -0.35), and the FI-2 (r(s) = -0.29 to -0.47) and disease activity measures (r(s) = 0.36-0.41). Cronbach's alpha coefficients for the 4 subscales varied between 0.85 and 0.95. Weighted kappa coefficients (K(w)) ranged between 0.77 and 0.93 for the 4 subscales and between 0.74 and 0.83 for the 4 single items without systematic variations (p > 0.05). CONCLUSION: This initial validation of the MAP indicates promising measurement properties for assessing limitations in activities of daily living and participation in patients with PM/DM in the United States.

Epidemiology of adult idiopathic inflammatory myopathies in a U.S. managed care plan.

INTRODUCTION: Idiopathic inflammatory myopathies have a reported incidence of 0.1 to 1 per 100,000 person-years and prevalence of 0.55 to 6 per 100,000 in the United States. METHODS: We retrospectively examined medical claims for adults aged ≥18 years with myositis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 710.3 [dermatomyositis], 710.4 [polymyositis], and 728.81 [interstitial myositis]) from 2003 to 2008 in a large US managed care database. RESULTS: The incidence and prevalence cohorts comprised 1,941 and 3,112 subjects, respectively. From 2003 to 2008, the adjusted annual incidence of myositis ranged from 5.8 to 7.9 per 100,000 person-years, and the annual prevalence of myositis ranged from 14.0 to 17.4 per 100,000. CONCLUSIONS: The incidence and prevalence of idiopathic inflammatory myopathies in the managed care plan studied was higher than previously reported in the United States. Because of the limitations inherent in claims analysis, additional research is needed to substantiate these results.

Healthcare costs of inflammatory myopathies.

OBJECTIVE: Little information exists regarding the economic burden related to inflammatory myopathies. Our objective was to estimate health services costs in a large, unselected, population-based sample of patients with inflammatory myopathies. METHODS: We identified subjects with polymyositis and dermatomyositis from administrative healthcare databases (covering all beneficiaries, about 7.5 million) in Quebec province, Canada. Average estimates of health services costs (physician visits, diagnostic tests and procedures, outpatient surgeries and procedures, acute care hospitalizations) for 2003 were calculated by multiplying health service use levels by the appropriate unit prices, determined from government fee schedules and other sources. Multiple linear regression analyses were performed to establish whether specific factors (age, sex, disease duration, region of residence, socioeconomic status, type of myositis, disease severity) were associated with cost. RESULTS: We identified 1102 subjects with inflammatory myopathy from January 1, 1989, to January 1, 2003. About two-thirds were women (68.9%); average age at case ascertainment was 57.4 years (SD 18.4). The average cost of all reimbursed health services, in 2008 Canadian dollars, was $4099 per patient (SD $9639). Costs increased with age, and were highest early in the disease course. Greater disease severity (defined as the need for prior hospitalization for myositis) was also a strong predictor of both physician costs and total costs. CONCLUSION: These results indicate significant economic burden related to inflammatory myopathies, with important demographic predictors. Our estimates suggest that the health services costs in inflammatory myopathies may equal, or exceed, those of other serious diseases, such as rheumatoid arthritis and systemic sclerosis.

Review of the classification and assessment of the cutaneous manifestations of the idiopathic inflammatory myopathies.

Adult and juvenile dermatomyositis, polymyositis and myositis overlapping with another connective tissue disease are rare systemic autoimmune diseases with a primary feature of weakness and muscle inflammation. Cutaneous findings specific to the underlying condition are present in many patients with these disorders. Some lesions are highly characteristic of the idiopathic inflammatory myopathies (IIM), especially in dermatomyositis. Some cutaneous findings are common but not specific to the IIM and others are less frequently observed in patients with these illnesses. Many of these manifestations also have different grades of disease activity or damage. This photoessay reviews the classification and assessment of the cutaneous manifestations of the IIM and presents example photographs of many of the lesions of adult and juvenile IIM accumulated from the clinical experience of international experts in these conditions. The purpose of this work is to facilitate better recognition of the diverse cutaneous manifestations associated with these inflammatory myopathies.

Assessment of an infectious disease history preceding juvenile dermatomyositis symptom onset.

OBJECTIVES: A number of studies have looked at the role of infectious diseases in triggering juvenile dermatomyositis (JDM). Previous studies have found a moderately high frequency of infectious symptoms prior to disease onset; however, no specific pathogens could be identified. We sought to correlate preceding infectious symptoms with onset and outcomes of JDM. METHODS: We studied an inception cohort of all JDM cases diagnosed at The Hospital for Sick Children (SickKids) between 1988 and 2006. Data pertaining to symptoms at onset, diagnosis and disease outcomes were abstracted. Two independent paediatric infectious disease specialists reviewed all records of patients with symptoms or tests suggestive of infection. RESULTS: A total of 110 patients were reviewed; of these, 78 had sufficient information about disease onset for inclusion. Potential indications of an infectious process prior to JDM onset were found in 55/78 (71%) patients and were further evaluated for evidence of infection temporally associated with symptom onset. Features suggestive of infection prior to JDM symptom onset were found in 40/55 [probable (30/40) or possible (10/40)]. Most children with probable infections had respiratory illnesses [24/30 (80%)]. Fewer patients than expected had disease onset during summer months. The presence of an infection at onset was not found to be associated with differences in characteristics at diagnosis or disease outcomes. CONCLUSIONS: A substantial number of JDM patients have a clinical history consistent with an infection prior to onset. Newly diagnosed patients should undergo a full infectious disease assessment as part of their initial work-up; specific attention should be given to respiratory infections.

Bone mineral density in juvenile dermatomyositis: assessment using dual x-ray absorptiometry.

OBJECTIVE: To determine the bone mineral density (BMD) status of our juvenile dermatomyositis (DM) population and to compare the frequency of osteopenia in patients with active disease requiring corticosteroids with that in patients with inactive disease who are not receiving corticosteroids. METHODS: Medical charts of all children diagnosed as having juvenile DM at our institution between 1989 and 1999 were reviewed for demographic and clinical data, including disease activity and duration of corticosteroid therapy. BMD measurements of the lumbar spine (L1-L4) were performed using dual x-ray absorptiometry (DXA). Z scores were calculated from the BMD data for comparison with published normative data. RESULTS: A total of 15 patients were assessed: 10 with active disease, and 5 with inactive disease who had not taken corticosteroids for an average of 6.0 years (range 3.4-8.1 years). Baseline BMD measurements demonstrated osteopenia or frank osteoporosis in the majority of patients, including 6 of the 10 patients with active disease and 4 of the 5 patients whose disease was in remission. Fourteen patients had serial BMD measurements. Persistent or worsening osteopenia was documented in all patients who had ongoing active disease, except for 3 patients who had been treated with bisphosphonates because of vertebral compression fractures. CONCLUSION: Osteopenia is common in patients with juvenile DM, and it usually worsens with ongoing disease. It can persist for many years after the disease enters remission. Bisphosphonates appeared to beneficially affect bone mineralization in our patients. Treatment to prevent the long-term complications of osteoporosis in patients with juvenile DM should be considered and requires further study.

Risk assessment of polymyositis/dermatomyositis after treatment with injectable bovine collagen implants.

BACKGROUND: Questions have been raised about a possible relation between injectable collagen and polymyositis and dermatomyositis (PM/DM). Predictions of the prevalence of PM/DM have been based on anecdotal estimates of the duration of follow-up for the collagen-treated population. OBJECTIVE: Our purpose was to study the duration of follow-up for a large sample of collagen-treated patients. METHODS: Physicians in North America who purchased collagen implants during fiscal year 1988 were categorized according to collagen practice size; one third were randomly invited to participate in the study. RESULTS: Review of 2622 patient records yielded an average duration of follow-up of 4 years. CONCLUSION: Five-year incidence rates were used to estimate the expected number of cases of PM/DM in the collagen-treated population. Through June 1993 the expected number was 30.2. The number of confirmed cases after treatment was seven, less than one fourth of the number of cases expected for a model of the collagen-treated population, matched for age, sex, and race.