Treatment Response to Tumor Necrosis Factor Inhibitors and Methotrexate Monotherapy in Adults With Juvenile Idiopathic Arthritis: Data From NOR-DMARD.

OBJECTIVE: To compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA). METHODS: Adult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated. RESULTS: We identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6). CONCLUSION: TNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.

Does sarcopenia predict change in mobility after hip fracture? a multicenter observational study with one-year follow-up.

BACKGROUND: Patients with hip fracture frequently have sarcopenia and are at great risk of loss of mobility. We have investigated if sarcopenia predicts change in mobility after hip fracture. METHODS: This is a prospective, multicenter observational study with one-year follow-up. Patients with hip fracture who were community-living and capable of walking before the fracture were included at three hospitals in Norway (2011-2013). The primary outcome of the study was change in mobility, measured by the New Mobility Score (NMS). Sarcopenia was determined postoperatively by anthropometry, grip strength, and NMS. RESULTS: We included 282 participants and sarcopenia status was determined in 201, of whom 38% (77/201) had sarcopenia, 66% (128/194) had low muscle mass, 52% (116/222) had low grip strength and 8% (20/244) had low pre-fracture mobility (NMS < 5). Sarcopenia did not predict change in mobility (effect 0.2 points; 95% CI -0.5 to 0.9, P = 0.6), but it was associated with having lower mobility at one-year (NMS 5.8 (SD 2.3) vs. 6.8 (SD 2.2), P = 0.003), becoming a resident of a nursing home (odds ratio 3.2, 95% CI 0.9 to 12.4, P = 0.048), and the combined endpoint of becoming a resident of a skilled nursing home or death (odds ratio 3.6, 95% CI 1.2 to 12.2, P = 0.02). CONCLUSIONS: Sarcopenia did not predict change in mobility in the year after hip fracture.

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study.

BACKGROUND: Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. METHODS: A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. RESULTS: Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. CONCLUSIONS: Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.

Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study.

BACKGROUND: The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment. METHODS: Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses. RESULTS: Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication. CONCLUSIONS: The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.

Radiographic and clinical outcome in early juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3-year prospective study.

OBJECTIVE: To describe radiographic findings at disease onset and 3-year followup in patients with juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to assess radiographic progression and its predictors, and to prospectively assess clinical outcome and predictors of persistent disease at 3-year followup. METHODS: A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years. Radiographic examination was performed at baseline and 3-year followup of knees and ankles (all patients) and of other joints on clinical indication. Remission was defined as minimum 6 months without medication and no clinical signs of active disease. RESULTS: Radiographic abnormalities were found in 88% of the patients at onset and in 81% after 3 years. Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup. Knees, hands, and wrists had most frequently radiographic abnormalities. Radiographic progression occurred in 38% of the patients. Joints with swelling/osteoporosis on radiographs, young age, and a large number of mobility-restricted joints at baseline were predictors of radiographic progression. At 3 years, 26% of the patients were in remission and 75% had been treated with disease-modifying antirheumatic drugs. Reduced well-being, a large number of active joints and negative antinuclear antibody at baseline were predictors of persistent disease after 3 years. CONCLUSION: After 3 years most patients had radiographic abnormalities and persistent disease. Young age, many affected joints, reduced well-being, and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years.

Frequency of osteopenia in children and young adults with childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the frequency of osteopenia in patients with childhood-onset systemic lupus erythematosus (SLE) compared with that in healthy matched controls, and to evaluate the relationship between disease-related variables and bone mineral mass. METHODS: Bone mineral density (BMD) and bone mineral content (BMC) were measured in a cohort of 70 patients with childhood-onset SLE (mean +/- SD disease duration 10.8 +/- 8.3 years, mean +/- SD age 26.4 +/- 9.9 years) and 70 age- and sex-matched healthy controls. BMD and BMC of the femoral neck, lumbar spine, total body, and distal one-third of the radius were measured by dual x-ray absorptiometry. We investigated the relationship between BMC and the following disease variables: cumulative dose of corticosteroids, organ damage, current use of corticosteroids, use of cyclophosphamide, age at disease onset, and disease activity at the time of diagnosis. Biochemical markers of bone metabolism were also measured. RESULTS: BMD values for the lumbar spine and femoral neck were significantly lower in patients than in healthy controls. The reduction in BMD of the lumbar spine was significantly greater than that of the total body. In multiple linear regression analyses, a higher cumulative corticosteroid dose was significantly associated with lower BMC of the lumbar spine and femoral neck. Decreased lumbar spine BMC was also related to male sex. CONCLUSION: The frequency of osteopenia was higher in patients with childhood-onset SLE than in matched controls. The lumbar spine was the most seriously affected skeletal site, followed by the femoral neck. The cumulative dose of corticosteroids was shown to be an important explanatory variable for BMC values in the lumbar spine and femoral neck.

Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3 year prospective study.

OBJECTIVE: . To describe the 3 year disease course in early juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to compare the health status after 3 years of followup with that of normal controls, and to investigate the relationship between physical function at followup and disease characteristics recorded during the first 6 months. METHODS: One hundred and ninety-seven children (median age 6:6 yrs) with JRA and JSpA and disease duration <1.5 years were examined by a pediatric rheumatologist every 6 months for a median of 3.1 years. Controls were randomly selected from the National Population Register. Physical and psychosocial health was assessed by means of the Child Health Questionnaire and the Childhood Health Assessment Questionnaire (CHAQ). Disease course was analyzed by analysis of variance for repeated measurements. RESULTS: Health status and disease activity improved over time. Treatment with disease modifying antirheumatic drugs was started in 58% of the patients at baseline. Patients with persistent oligoarthritis had the most favorable disease course. The patients with juvenile ankylosing spondylitis (JAS), syndrome of seronegative enthesopathy and arthropathy (SEA), and rheumatoid factor (RF) positive polyarthritis had the poorest health status. A significant improvement for the whole group was observed after 3 years in all measures of disease activity and health status, except pain. Patients had poorer physical function and general health and more pain than controls. Predictors of reduced physical function at followup were a high CHAQ disability index and a poor well-being assessed during the first 6 months. CONCLUSION: Health status and disease activity improved over time in patients under medical treatment. The patients with JAS/SEA and RF positive polyarthritis had poorer health than the patients in other subtypes. A high disability index and a poor well-being at baseline predicted reduced physical function after 3 years.

A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis.

OBJECTIVE: To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. METHODS: We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. RESULTS: Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. CONCLUSION: Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course.

Frequency of osteopenia in adolescents with early-onset juvenile idiopathic arthritis: a long-term outcome study of one hundred five patients.

OBJECTIVE: To determine the frequency of low bone mineral content (BMC) and low bone mineral density (BMD) as long-term complications in adolescents with early-onset juvenile idiopathic arthritis (JIA), and to identify disease variables, patient characteristics, and biochemical bone markers related to low bone mass. METHODS: One hundred five (87%) of 121 adolescent patients with early-onset JIA (ages 13-19 years, 80 girls and 25 boys, mean age at onset of JIA 2.8 years), from a cohort first admitted to the hospital between 1980 and 1985, were assessed after a mean disease duration of 14.2 years. BMC and BMD of the total body, the lumbar spine at L2-L4, and the femoral neck were measured by dual-energy x-ray absorptiometry. Age- and sex-specific reference values from a pooled, healthy reference population were used to calculate Z scores. Low bone mass was defined as a Z score less than -1 SD. RESULTS: Among the 103 adolescent JIA patients who underwent total-body imaging, 41% had low total-body BMC and 34% had low total-body BMD. Compared with adolescent JIA patients who had normal total-body BMC, those with low BMC had lower mean weight (P < 0.001), height (P < 0.001), lean mass (P < 0.001), and remission rates (P = 0.016), had longer duration of active disease (P = 0.013), had higher numbers of active and mobility-restricted joints (P < 0.001 and P = 0.001, respectively), had more disability (P = 0.011), had higher frequencies of joint erosions (P < 0.001), and had higher erythrocyte sedimentation rates (P = 0.033). In multiple linear regression analyses of total-body BMC, 88% of the variance was explained by the duration of active disease, the number of joints with restricted mobility, the bone area, urinary deoxypyridinoline values, age, weight, and height. CONCLUSION: Forty-one percent of the adolescents with early-onset JIA had low bone mass >11 years after disease onset. The development of low total-body BMC was related to the duration of active disease, disease severity, measures of bone resorption, weight, and height.

Measuring health status in early juvenile idiopathic arthritis: determinants and responsiveness of the child health questionnaire.

OBJECTIVE: To assess the determinants and responsiveness of the Norwegian version of the Child Health Questionnaire (CHQ) in patients with early juvenile idiopathic arthritis (JIA) and to compare health status in patients and controls. METHODS: A total of 116 children (median age 8.4 yrs) with JIA and < 2.5 years of disease duration (median 11.0 mo) were examined by a pediatric rheumatologist and reassessed after a median of 10.0 months. Physical and psychosocial health were assessed by means of the CHQ, which provides summary scores for physical and psychosocial health, the Childhood Health Assessment Questionnaire (CHAQ), and the Child Behavior Checklist (CBCL, n = 32). Matched controls (n = 116), randomly selected from the general population, completed the CHQ at baseline. RESULTS: The patients with JIA had poorer physical health and slightly impaired psychosocial health compared with the controls [41.2 +/- 13.6 vs 55.2 +/- 7.3 (p < 0.001) and 51.0 +/- 7.5 vs 54.1 +/- 5.7 (p = 0.002), respectively]. The most important determinants of the CHQ physical summary score were the child's pain, morning stiffness, the CHAQ disability index, erythrocyte sedimentation rate (ESR), overall well-being, and physician's global assessment of disease activity. The psychosocial summary score correlated with the CBCL level of internalizing, externalizing, and total behavior problems. The standardized response mean for the physical summary score was large (0.96) for those who improved, and moderate (-0.60) for those who became worse. CONCLUSION: The CHQ discriminated between patients with early JIA and controls. The most important determinants of the CHQ physical summary score were the child's pain, morning stiffness, CHAQ, ESR, overall well-being, and physician's global assessment of disease activity. The CHQ was sensitive to clinical changes in children with JIA.

Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years.

OBJECTIVE: To describe the physical and psychosocial outcome in patients with juvenile rheumatoid arthritis (JRA), compared with subjects in the general population, and to determine patient characteristics, HLA alleles, and disease variables within the first 6 months of disease onset that predict persistent disease, joint erosions, and physical disability. METHODS: A cohort of 268 (85%) of 316 patients with JRA first admitted to the hospital between 1980 and 1985 were examined after a median of 14.9 years (range 11.7-25.1) of disease duration. Controls matched for age, sex, and geographic region were randomly selected from the general population. Patients' medical records were retrospectively reviewed. Clinical examinations and radiographs of the hips, ankles, and affected joints were obtained. HLA-DRB1 and DPB1 alleles were determined by genotyping and HLA-B27 by serologic testing. Physical and psychosocial health status was assessed using the Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ). RESULTS: At followup, 133 patients with JRA (50%) were in remission, 63 (24%) had developed joint erosions, and 93 (36%) had impaired physical functioning (HAQ > 0.0). Patients had greater disability, more bodily pain, and poorer general health than controls. Comparable levels of education, social function, and mental health were found, but the patients had higher rates of unemployment than controls (19% vs 7%; p < 0.001). Predictors of persistent disease and joint erosions were: young onset age and large numbers of affected joints, long duration of elevated erythrocyte sedimentation rate (ESR), and positive IgM rheumatoid factor (RF) within the first 6 months. Additionally, persistent disease was predicted by the presence of DRB1*08, and joint erosions were predicted by symmetric arthritis and DRB1*08 and HLA-B27 in combination. DRB1*01 was a predictor of joint erosions in the pauciarticular onset type (n = 163). Predictors of physical disability were: female sex, symmetric arthritis, hip joint involvement, long duration of elevated ESR and IgM RF. CONCLUSION: Compared with healthy controls, patients with JRA had impaired physical health and lower employment rates after more than 11 years of disease duration. Elevated ESR, extensive and symmetric arthritis, positive IgM RF, DRB1*08, DRB1*01, HLA-B27 and DRB1*08 in combination, early onset, and female sex were early risk factors for an unfavorable outcome.

The influence of patient characteristics, disease variables, and HLA alleles on the development of radiographically evident sacroiliitis in juvenile idiopathic arthritis.

OBJECTIVE: To assess the frequency of sacroiliitis and the radiographic and clinical outcome in juvenile idiopathic arthritis (JIA) and determine patient characteristics, early disease variables, and genetic markers that predict development of sacroiliitis. METHODS: We performed a retrospective cohort study of 314 (79%) of the 400 JIA patients first admitted to the hospital between 1980 and 1985. The participants were examined after a median disease duration of 14.9 years (range 11.7-25.1). Radiographs of the sacroiliac joints, hips, ankles, and tarsi were obtained and studied in a blinded manner by 2 radiologists. The presence of HLA-DRB1 and DPB1 alleles was determined by genotyping and that of HLA-B27 by serologic testing. Variables relating to the onset and course of the disease were obtained by chart reviews. RESULTS: Twenty (6%) of the JIA patients developed radiographic sacroiliitis according to the New York criteria. In 9 patients (45%), sacroiliitis had not been demonstrated before the followup examination. At followup, spinal flexion (lateral and anterior) was reduced in 70-75% of patients with sacroiliitis and in 30-35% of those without sacroiliitis. Compared with the JIA patients without sacroiliitis, those with sacroiliitis more frequently had inflammatory back pain, enthesitis, radiographic changes in the hips and calcanei, erosions of any peripheral joint, and uveitis. Predictors of sacroiliitis were HLA-B27, absence of DPB1*02, hip joint involvement within the first 6 months, and disease onset after age 8 years. The following factors were more common among patients in whom sacroiliitis developed than in other JIA patients: DRB1*04, male sex, family history of ankylosing spondylitis, psoriasis, inflammatory back pain, and enthesitis within the first 6 months. CONCLUSION: In the current study, radiographically evident sacroiliitis had developed in 6% of JIA patients after a median disease duration of 14.9 years. HLA-B27, absence of DPB1*02, late onset of disease, and early hip involvement were predictors of sacroiliitis.

Minor impact of juvenile arthritis on nutritional status in young adult patients.

OBJECTIVE: Growth abnormalities and poor nutritional status have been reported in children with juvenile idiopathic arthritis (JIA). The aim of this study was to evaluate the impact of juvenile chronic rheumatic disease on current nutritional status in adult patients in remission or with active disease. METHODS: One hundred thirty-eight women and 82 men, aged >20 years, with JIA were studied after a mean disease duration of 15.5 +/- 2.3 years. Eighty-four (61%) of the women and 49 (60%) of the men were in remission. Forty-one healthy women and 54 healthy men served as a reference group. Body composition was analyzed by dual-energy x-ray absorptiometry. RESULTS: There was no difference in height or body mass index (BMI) between patients and healthy subjects. However, female patients with systemic disease had significantly reduced BMI compared with those with pauciarticular JIA (P < 0.001), and female patients who used or had been using corticosteroids had significantly lower weight, height, and BMI compared with the patients who had never used corticosteroids (P < 0.05). Female patients in remission had significantly more lean body mass compared with healthy controls (P < 0.05) and significantly less body fat was found in both women and men (P < 0.01 for both). Patients with active disease had the same amount of lean body mass as the healthy controls, but significantly less body fat (P < 0.05 for women and P < 0.01 for men). CONCLUSION: Adult patients with JIA had attained normal height, weight, and BMI, with the exception of women with systemic JIA and those who were using or had used corticosteroids. Patients with JIA in remission seemed to have a better nutritional status than healthy subjects.