Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Objective

To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (JIA) who develop MAS while treated with biologic medications.

Methods

A systematic literature review was performed to identify patients with MAS while being treated with interleukin (IL)‐1 and IL‐6 blocking agents. Clinical and laboratory information was compared to a large previously compiled historical cohort.

Results

Eighteen publications were identified, and after removing duplicates, 35 patients treated with canakinumab and 49 patients with tocilizumab were available for analysis; 5 anakinra‐treated patients were excluded due to limited numbers. MAS classification criteria were less likely to classify tocilizumab‐treated patients as having MAS compared to the historical cohort or canakinumab‐treated patients (56.7%, 78.5%, and 84%, respectively; P < 0.01). Patients who developed MAS while treated with canakinumab trended towards lower ferritin at MAS onset than the historical cohort (4,050 versus 5,353 ng/ml; P = 0.18) but had no differences in other cardinal clinical or laboratory features. In comparison, patients who developed MAS while treated with tocilizumab were less likely febrile and had notably lower ferritin levels (1,152 versus 5,353 ng/ml; P < 0.001). Other features of MAS were more pronounced in patients treated with tocilizumab, including lower platelet counts, lower fibrinogen, and higher aspartate aminotransferase levels. Mortality rates for patients with MAS treated with tocilizumab or canakinumab were not significantly different from the historical cohort.

Conclusion

These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologic agents.

     

Impact of Uveitis on Quality of Life in Adult Patients With Juvenile Idiopathic Arthritis

Objective

To establish the impact of uveitis on the quality of life (QoL) in adult patients with juvenile idiopathic arthritis (JIA ).

Methods

Adult patients with a history of JIA , both with (n = 31) or without (n = 51) chronic anterior uveitis, were included. Their scores on 3 validated QoL questionnaires (National Eye Institute Visual Functioning Questionnaire [NEI VFQ ‐25], Medical Outcomes Study 36‐Item Short Form health survey [SF ‐36], and EuroQol 5‐domain questionnaire [EQ ‐5D]) were analyzed to find factors that could influence QoL.

Results

The median overall composite score (OCS ) of the NEI VFQ ‐25 was significantly worse in the uveitis group compared to the non‐uveitis group (respectively, 83.4 [range 15.2–94.7] and 94.9 [range 46.3–100]; P < 0.001). Nearly all subscale scores were lower in patients with uveitis than in patients without uveitis (P < 0.001 for all). After adjusting for duration of arthritis, JIA subtype, arthritis onset before or after 1990, and the use of systemic immunomodulatory medication, the QoL was still worse in patients with uveitis (NEI VFQ ‐25 OCS regression coefficient = ?11.7; P = 0.002). No significant differences were found between the groups for the SF ‐36 and the EQ ‐5D. In the total JIA group, the use of systemic medication appeared to negatively influence some general QoL scores.

Conclusion

Having a history of uveitis has a substantial negative effect on the vision‐related QoL in JIA in adulthood, despite good visual acuity. General QoL scores did not differ between uveitis and non‐uveitis patients, but the use of systemic immunomodulatory treatment, independent of uveitis, did negatively influence general QoL scores in adult JIA patients.

     

Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration

Objective

To define candidate criteria within multiphase development of systemic lupus erythematosus (SLE) classification criteria, jointly supported by the American College of Rheumatology and the European League Against Rheumatism. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a nominal group technique exercise. Our objectives were to apply an evidence‐based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains.

Methods

A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of antinuclear antibody (ANA) as an entry criterion and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process.

Results

Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp‐2 cells immunofluorescence) as an entry criterion and to have 7 clinical and 3 immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified.

Conclusion

Using a data‐driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale.

     

Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration

Objective

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

Methods

We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates.

Results

The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIA patients (Mantel‐Cox χ² = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel‐Cox χ² = 9.06, P < 0.002). No other clinical variable was significantly associated with a long‐lasting remission.

Conclusion

Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

     

Depression Risk in Young Adults With Juvenile‐ and Adult‐Onset Lupus: Twelve Years of Followup

Objective

To compare major depression risk among young adults with juvenile‐onset and adult‐onset systemic lupus erythematosus (SLE), and to determine demographic and health‐related predictors of depression.

Methods

Young adults with SLE ages 18–45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002–2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale (CES‐D), and self‐report measures of sociodemographics and health characteristics. Juvenile‐onset SLE was defined as age <18 years at diagnosis (n = 115). Repeated‐measures analysis was performed to assess the risk for major depression (CES‐D ≥24) at any point in study, and logistic regression was used to assess for recurrent (present on ≥2 assessments) major depression.

Results

Major depression was experienced by 47% of the cohort at least once during the 12‐year study period. In adjusted analyses, juvenile‐onset SLE patients had an increased risk of having a major depressive episode (odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.0–2.7]) and recurrent episodes (OR 2.2 [95% CI 1.2–4.3]), compared to participants with adult‐onset SLE. Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile‐onset SLE patients had a higher risk of major depression across all educational groups.

Conclusion

Young adults with SLE, particularly those with juvenile‐onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes.

     

Radiographic Progression in Psoriatic Arthritis Achieving a Good Response to Treatment: Data Using Newer Composite Indices of Disease Activity

Objective

To compare radiographic outcomes according to the magnitude of the response utilizing 3 new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score [PASDAS], the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise [GRACE], and the Disease Activity in PsA [DAPSA]).

Methods

The data were taken from the GO‐REVEAL data set, a large randomized, double‐blind study that evaluated the safety and efficacy of 2 doses of the tumor necrosis factor inhibitor golimumab in subjects with active psoriatic arthritis (PsA). Response criteria at 24 weeks were applied across the whole data set, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed using the modified Sharp/van der Heijde method for PsA.

Results

Overall, for each measure, radiographic progression was significantly greater in subjects with a moderate or poor outcome, and absent in those with a good outcome. The proportion of subjects without radiographic progression in the good outcome group was 83% using the PASDAS (χ² = 7.9; P = 0.02), 80% using the GRACE (χ² = 5.8; P = 0.05), and 76% using the DAPSA (χ² = 3.4; P = 0.19).

Conclusion

Response criteria for disease‐specific composite measures enable separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies, as well as in the clinic.

     

Evaluation of a Methodologic Approach to Define an Inception Cohort of Rheumatoid Arthritis Patients Using Administrative Data

Objective

Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data.

Methods

Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims‐based algorithm for incident RA.

Results

Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68–81%. A 2‐year clean period free of all RA‐related diagnoses and medications was somewhat more optimal although, by comparison, a 1‐year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis.

Conclusion

Claims‐based algorithms can accurately identify incident RA.

     

Multicenter Delphi Exercise to Identify Important Key Items for Classifying Systemic Lupus Erythematosus

Objective

The American College of Rheumatology and the European League Against Rheumatism embarked on a project to reevaluate classification criteria for systemic lupus erythematosus (SLE). The first phase of the classification project involved generation of a broad set of items potentially useful for classification of SLE and their selection for use in a subsequent forced‐choice decision analysis.

Methods

A large international group of expert lupus clinicians was invited to participate in a 2‐step process to generate, rate, and select items based on their importance in diagnosing early and established SLE, via a web‐based survey.

Results

A total of 135 and 147 experts were invited to participate in the item‐generation and item‐reduction process, respectively. Of 145 items generated, item reduction resulted in 40 candidate items moving forward to the next phase. Key features for classifying both early and established SLE included characteristic autoantibodies, specific renal features, and skin manifestations. A small majority (51%) stated that 1 organ system would be sufficient for classifying SLE, but that additional typical laboratory features (antinuclear antibody, anti–double‐stranded DNA) would be required. Notably, 85% of the expert group would positively classify SLE if renal pathology alone showed lupus nephritis.

Conclusion

The Delphi exercise resulted in a set of 40 candidate criteria for the classification of SLE for subsequent assessment. This study comprised the largest panel ever involved in the development of SLE classification criteria, providing a broadly representative view of the current approach to classification of SLE.

     

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions

Objective

To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies.

Methods

Virtual and face‐to‐face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions.

Results

Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response.

Conclusion

Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.

     

From Childhood to Adulthood: Disease Activity Trajectories in Childhood‐Onset Systemic Lupus Erythematosus

Objective

No previous study has studied the longitudinal disease course of childhood‐onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories.

Methods

This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model.

Results

A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient‐years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years.

Conclusion

There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories.

     

Comparative Effectiveness of Mycophenolate Mofetil for the Treatment of Juvenile‐Onset Proliferative Lupus Nephritis

Objective

Although juvenile‐onset proliferative lupus nephritis (PLN ) leads to significant morbidity and mortality, there is no clinical trials–based evidence to support the treatment effectiveness of any therapy for juvenile‐onset PLN . Marginal structural models enable us to estimate treatment effectiveness using observational data while accounting for confounding by indication.

Methods

We used prospectively collected data to examine the effect of mycophenolate mofetil (MMF ), compared to the use of other therapies, on the long‐term outcome of a juvenile‐onset PLN cohort (age at PLN onset <18 years). The major outcome variable was the estimated glomerular filtration rate (GFR ) using the revised Schwartz formula. Confounding by indication was corrected for marginal structural model.

Results

A total of 172 subjects with juvenile‐onset PLN , with a mean followup duration of approximately 4 years, were included. Overall, MMF was superior to other therapies, with a relative effect estimate for MMF of 1.06, i.e., 6% better estimated GFR on average (95% confidence interval 0.7, 11.3), corrected for potential confounding by indication. We found that beginning in year 4 there was a significant improvement in estimated GFR in the patients who were treated with MMF versus other therapies. This improvement was maintained until the end of the study.

Conclusion

MMF was more beneficial than other therapies in improving/maintaining long‐term renal function in patients with juvenile‐onset PLN up to a maximum followup of 7 years. This finding is consistent with evidence from adult PLN clinical trials.

     

Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients With Psoriatic Disease: A Meta‐Epidemiologic Study

Objective

To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease.

Methods

We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta‐regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs.

Results

Forty‐eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70–2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64–3.97]). The eligibility criteria “targeted therapy history,” “minimum required disease duration,” “required negative rheumatoid factor,” and “required Classification Criteria for Psoriatic Arthritis criteria” were of importance for achieving ACR20 in PsA. The eligibility criterion “minimum required disease duration” was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time‐point‐of‐retention reporting (adaptive trials).

Conclusion

From this exploratory meta‐epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

     

Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease‐Modifying Antirheumatic Drugs: A Systematic Review and Meta‐Analysis

Objective

To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease‐modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis.

Methods

We conducted a systematic review and meta‐analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non‐TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle‐Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman‐Tukey‐type arcsine square root transformation, using a random‐effects model.

Results

Twenty‐five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8–2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5–2.6]), non‐TNF biologics (6.1% [95% CI 0.0–16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2–4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1–15.5]) than in those who did not (14.6% [95% CI 4.3–29.0]).

Conclusion

We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

     

Association Between Dose of Glucocorticoids and Coronary Artery Lesions in Kawasaki Disease

Objective

Several studies revealed the efficacy of glucocorticoids on prevention of coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown.

Methods

Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal‐dose (prednisolone 0.5–4.0 mg/kg/day) or high‐dose (methylprednisolone 10–40 mg/kg/day) glucocorticoids. We investigated risks of CALs and readmission, total hospitalization cost, and length of hospital stay in the acute phase of KD using propensity score matching, stabilized propensity‐score inverse probability of treatment weighting, and instrumental variable methods.

Results

We identified a total of 3,220 patients with KD who were treated with normal‐dose (n = 2,453) or high‐dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin. One‐to‐one propensity‐matched analyses with 744 pairs demonstrated no significant differences between the normal‐dose and the high‐dose groups in risk of CALs (risk ratio [RR] 0.83, 95% confidence interval [95% CI] 0.49, 1.40) and risk of readmissions (RR 0.85, 95% CI 0.65, 1.11). Stabilized propensity‐score inverse probability weighting and instrumental variable analyses showed similar results to the propensity score matching analyses.

Conclusion

Risks of CALs and readmissions and total hospitalization costs were similar between the normal‐dose and the high‐dose glucocorticoids groups for patients with KD, whereas total length of hospital stay was shorter in the high‐dose group than that in the normal‐dose group.

     

Impact of Disease Severity,Illness Beliefs,and Coping Strategies on Outcomes in Psoriatic Arthritis

Objective

Little is known about how people with psoriatic arthritis (PsA) cope with and manage their condition, but data show that psychological problems are underrecognized and undertreated. The Common Sense Self‐Regulatory Model (CS‐SRM) suggests illness beliefs, mediated by coping, may influence health outcomes. The study aimed to investigate the roles of disease severity, illness beliefs, and coping strategies in predicting depression, anxiety, and quality of life (QoL) in people with PsA. Additionally, we aimed to assess the role of depression and anxiety in predicting QoL.

Methods

We conducted a cross‐sectional observational study, where adults with PsA (n = 179) completed validated measures of predictor (illness beliefs, coping strategies, disease severity) and outcome variables (depression, anxiety, QoL) using an online survey distributed via social media.

Results

The participants were a community sample of 179 adults with PsA, ages 20 to 72 years (77.1% female). After controlling for disease severity, hierarchical multiple regression models indicated that more negative beliefs about consequences and behavioral disengagement as a coping method predicted levels of depression, and self‐blame predicted anxiety. Beliefs about consequences and the presence of depression predicted quality of life scores after controlling for disease severity.

Conclusion

This study offers support for the use of the CS‐SRM in explaining variation on psychological outcomes in individuals with PsA. The illness beliefs and coping strategies identified as predictors in this article are potential targets for interventions addressing PsA‐related distress and QoL.

     

Disparities in Total Knee Replacement: Population Losses in Quality‐Adjusted Life‐Years Due to Differential Offer,Acceptance, and Complication Rates for African Americans

Objective

Total knee replacement (TKR) is an effective treatment for end‐stage knee osteoarthritis (OA). American racial minorities undergo fewer TKRs than whites. We estimated quality‐adjusted life‐years (QALYs) lost for African American knee OA patients due to differences in TKR offer, acceptance, and complication rates.

Methods

We used the Osteoarthritis Policy Model, a computer simulation of knee OA, to predict QALY outcomes for African American and white knee OA patients with and without TKR. We estimated per‐person QALYs gained from TKR as the difference between QALYs with current TKR use and QALYs when no TKR was performed. We estimated average, per‐person QALY losses in African Americans as the difference between QALYs gained with white rates of TKR and QALYs gained with African American rates of TKR. We calculated population‐level QALY losses by multiplying per‐person QALY losses by the number of persons with advanced knee OA. Finally, we estimated QALYs lost specifically due to lower TKR offer and acceptance rates and higher rates of complications among African American knee OA patients.

Results

African American men and women gain 64,100 QALYs from current TKR use. With white offer and complications rates, they would gain an additional 72,000 QALYs. Because these additional gains are unrealized, we call this a loss of 72,000 QALYs. African Americans lose 67,500 QALYs because of lower offer rates, 15,800 QALYs because of lower acceptance rates, and 2,600 QALYs because of higher complication rates.

Conclusion

African Americans lose 72,000 QALYs due to disparities in TKR offer and complication rates. Programs to decrease disparities in TKR use are urgently needed.

     

Positive association of SLC26A2 gene polymorphisms with susceptibility to systemic‐onset juvenile idiopathic arthritis

Objective

To investigate SLC26A2, the gene that causes diastrophic dysplasia, in juvenile idiopathic arthritis (JIA).

Methods

Nine polymorphisms across the SLC26A2 gene locus were investigated using MassArray genotyping in 826 UK Caucasian JIA cases and 617 ethnically matched healthy controls.

Results

Significant associations between multiple single‐nucleotide polymorphisms (SNPs) across SLC26A2 and systemic‐onset JIA were found. In each case, homozygosity for the minor allele conferred the increased risk of disease susceptibility: rs1541915 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4–3.7, P = 0.0003), rs245056 (OR 2.8, 95% CI 1.7–4.6, P = 0.00002), rs245055 (OR 2.5, 95% CI 1.2–5.0, P = 0.004), rs245051 (OR 2.3, 95% CI 1.4–3.7, P = 0.0005), rs245076 (OR 2.7, 95% CI 1.3–5.4, P = 0.0015), and rs8073 (OR 2.3, 95% CI 0.9–5.6, P = 0.04).

Conclusion

These findings show the value of using monogenic disease loci as candidates for investigation in JIA. We identified a subgroup‐specific association between SNPs within the SLC26A2 gene and systemic‐onset JIA. Our findings also highlight systemic‐onset JIA as being a distinctly different disease from that in the other JIA subgroups.

     

Physical Functioning,Pain, and Health‐Related Quality of Life in Adults With Juvenile Idiopathic Arthritis: A Longitudinal 30‐Year Followup Study

Objective

To describe physical functioning, pain, and health‐related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQoL after 30 years of disease.

Methods

Patients (n = 176) clinically examined after 15 years were reassessed using the Health Assessment Questionnaire disability index (HAQ DI), the visual analog scale pain subscale (VAS pain), and the Medical Outcomes Study Short Form 36 (SF‐36) after 23 years and 30 years. Patients with signs of active disease after a minimum of 15 years were clinically examined again at 30 years. Patients were compared to matched controls.

Results

At the 30‐year followup, 82 patients (47%) had HAQ DI scores >0, and the median VAS pain score in patients was 0.6 (range 0–10). Patients had lower SF‐36 physical component summary (PCS) scores compared with controls (P < 0.001), and this was evident for patients both with and without clinical remission (P ≤ 0.01). No group differences were found in SF‐36 mental component summary scores. Patients also scored worse than controls on all SF‐36 subscales (P ≤ 0.01) except mental health. PCS scores worsened significantly between the 15‐ and 30‐year followup time points (P = 0.001). Worse HAQ DI, VAS pain, and patient's global assessment of well‐being scores, and receiving disability/social living allowance at 30 years, were correlated with lower PCS scores. Worse HAQ DI, patient's global assessment of well‐being, and VAS fatigue scores at 15‐year followup predicted lower PCS scores at 30‐year followup.

Conclusion

JIA had a detrimental effect on physical HRQoL as measured by the PCS of the SF‐36. The strongest correlates were physical disability, pain, fatigue, well‐being, and receiving disability/social living allowance.