A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial.

OBJECTIVES: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). METHODS: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. RESULTS: The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. CONCLUSIONS: IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.

An open-label extension study to demonstrate long-term safety and efficacy of ABP 501 in patients with rheumatoid arthritis.

BACKGROUND: ABP 501 was evaluated in a phase 3 single-arm, open-label extension (OLE) study to collect additional safety and efficacy data in patients with rheumatoid arthritis (RA). METHODS: Subjects completing the final visit in the parent phase 3 randomized, double-blind, controlled equivalence study comparing the efficacy and safety of the biosimilar ABP 501 with adalimumab reference product (RP) were enrolled in this open-label extension (OLE) study. All subjects received 40 mg ABP 501 every other week for 68 weeks. Key safety endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and anti-drug antibody (ADA) incidences. Efficacy endpoints included ACR20 (at least 20% improvement in American College of Rheumatology core set measurements from baseline) and Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) change from baseline. RESULTS: Among 466/467 patients treated with ABP 501, 229 transitioned from the ABP 501 arm of the parent study (ABP 501/ABP 501) and 237 from the adalimumab RP arm (RP/ABP 501); 412/467 (88.2%) patients completed the study. The overall TEAE incidence was 63.7% (297/466); grade ≥ 3 TEAE incidence was 9.0% (42/466). The incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). The SAE incidence was 9.9% (46/466). Overall, 18.2% (85/466) of subjects developed binding ADAs and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The ACR20 response rate was 73.3% (340/464 subjects) at OLE baseline, and 78.8% (327/415 subjects) at week 70 of the OLE study. The overall mean DAS28-CRP change from the parent study baseline was - 2.25 at the OLE study baseline (n = 440), - 2.36 at week 4 (n = 463), - 2.41 at week 24 (n = 450), - 2.55 at week 48 (n = 433), and - 2.60 at week 70 (n = 412). Efficacy was maintained throughout the study. CONCLUSIONS: Efficacy previously demonstrated in the parent study was maintained in this OLE study with no new safety findings. Long-term safety, immunogenicity, and efficacy were similar in the ABP 501/ABP 501 and RP/ABP 501 groups. The single switch from RP to ABP 501 did not impact immunogenicity. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02114931.

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). METHODS: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. RESULTS: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging-evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). CONCLUSION: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.

Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.

BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. METHODS: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. FINDINGS: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. INTERPRETATION: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. FUNDING: Eli Lilly and Company.

Validity and measurement precision of the PROMIS physical function item bank and a content validity-driven 20-item short form in rheumatoid arthritis compared with traditional measures.

OBJECTIVE: To evaluate the content validity and measurement properties of the Patient-Reported Outcome Measurement Information System (PROMIS) physical function item bank and a 20-item short form in patients with RA in comparison with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36) physical functioning scale (PF-10). METHODS: The content validity of the instruments was evaluated by linking their items to the International Classification of Functioning, Disability and Health (ICF) core set for RA. The measures were administered to 690 RA patients enrolled in the Dutch Rheumatoid Arthritis Monitoring registry. Measurement precision was evaluated using item response theory methods and construct validity was evaluated by correlating physical function scores with other clinical and patient-reported outcome measures. RESULTS: All 207 health concepts identified in the physical function measures referred to activities that are featured in the ICF. Twenty-three of 26 ICF RA core set domains are featured in the full PROMIS physical function item bank compared with 13 and 8 for the HAQ-DI and PF-10, respectively. As hypothesized, all three physical function instruments were highly intercorrelated (r 0.74-0.84), moderately correlated with disease activity measures (r 0.44-0.63) and weakly correlated with age (rs 0.07-0.14). Item response theory-based analysis revealed that a 20-item PROMIS physical function short form covered a wider range of physical function levels than the HAQ-DI or PF-10. CONCLUSION: The PROMIS physical function item bank demonstrated excellent measurement properties in RA. A content-driven 20-item short form may be a useful tool for assessing physical function in RA.

Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging.

While many age-associated immune changes have been reported, a comprehensive set of metrics of immune aging is lacking. Here we report data from 243 healthy adults aged 40-97, for whom we measured clinical and functional parameters, serum cytokines, cytokines and gene expression in stimulated and unstimulated PBMC, PBMC phenotypes, and cytokine-stimulated pSTAT signaling in whole blood. Although highly heterogeneous across individuals, many of these assays revealed trends by age, sex, and CMV status, to greater or lesser degrees. Age, then sex and CMV status, showed the greatest impact on the immune system, as measured by the percentage of assay readouts with significant differences. An elastic net regression model could optimally predict age with 14 analytes from different assays. This reinforces the importance of multivariate analysis for defining a healthy immune system. These data provide a reference for others measuring immune parameters in older people.

Establishing a Common Metric for Physical Function: Linking the HAQ-DI and SF-36 PF Subscale to PROMIS(®) Physical Function.

BACKGROUND: Physical function (PF) is a common health concept measured in clinical trials and clinical care. It is measured with different instruments that are not directly comparable, making comparative effectiveness research (CER) challenging when PF is the outcome of interest. OBJECTIVE: Our goal was to establish a common reporting metric, so that scores on commonly used physical function measures can be converted into PROMIS scores. DESIGN: Following a single-sample linking design, all participants completed items from the NIH Patient Reported Outcomes Measurement Information System (PROMIS®) Physical Function (PROMIS PF) item bank and at least one other commonly used "legacy" measure: the Health Assessment Questionnaire (HAQ) or the Short Form-36 physical function ten-item PF scale (SF-36 PF). A common metric was created using analyses based on item response theory (IRT), producing score cross-walk tables. PARTICIPANTS: Participants (N = 733) were part of an internet panel, many of whom reported one or more chronic health conditions. MAIN MEASURES: PROMIS PF, SF-36 PF, and the HAQ-Disability Index (HAQ-DI). RESULTS: Our results supported the hypothesis that all three scales measure essentially the same concept. Cross-walk tables for use in CER are therefore justified. CONCLUSIONS: HAQ-DI and SF-36 PF results can be expressed on the PROMIS PF metric for the purposes of CER and other efforts to compare PF results across studies that utilize any one of these three measures. Clinicians seeking to incorporate PROs into their clinics can collect patient data on any one of these three instruments and estimate the equivalent on the other two.

Chronic kidney disease as a risk factor for incident gout among men and women: retrospective cohort study using data from the Framingham Heart Study.

OBJECTIVES: Historically, the nature of association between chronic kidney disease (CKD) and gouty arthritis has been unclear. The goal of the present study was to test the hypothesis that CKD is an independent risk factor for developing incident gout. DESIGN: Patients were from the original Framingham Heart Study cohort. Using Cox proportional hazard models we estimated the HR of CKD to incident gout among men and women separately after adjusting for age, alcohol consumption, smoking, hypertension, diabetes and body mass index. SETTINGS: Patients were all from Framingham, Massachusetts, USA. PARTICIPANTS: Excluding patients who had CKD in the first visit from this study, 2159 men and 2558 women were selected covering a 54-year period (1948-2002). RESULTS: There were 371 incident cases (231 men and 140 women) of gout over the follow-up of 140,421 person-years. Incidence rates of gout per 1000 person-years for participants with and without CKD were 6.82 (95% CI 5.10 to 9.10) and 2.43 (2.18 to 2.71), respectively. In multivariable Cox models, CKD was associated with gout, with a HR of 1.88 (1.13 to 3.13) among men and 2.31 (1.25 to 4.24) among women. Additional analyses using alternate definitions for CKD and cross-sectional study did not change the results. Sensitivity analysis suggested that the observed findings might be an underestimate of the true relative risk. CONCLUSIONS: The present study provides epidemiological evidence to support the notion that CKD is a risk factor for gout.

Cigarette smoking is associated with a reduction in the risk of incident gout: results from the Framingham Heart Study original cohort.

OBJECTIVE: Cigarette smoking is correlated with other risk factors for gout such as adiposity and alcohol intake. The goal of this study was to study the direction and magnitude of association between cigarette smoking and risk for gout. METHODS: We analysed 54-year follow-up data (1948-2002) for 2279 men and 2785 women who were gout-free at their first assessment as a part of the Framingham Heart Study. Using Cox proportional hazards models we estimated the association between cigarette smoking and incident gout among men and women separately after adjusting for age, BMI, alcohol intake, hypertension, kidney disease and diabetes. RESULTS: There were 399 incident cases (249 men and 150 women) of gout over 151 058 person-years of observation. Incidence rates of gout per 1000 person-years for smokers and non-smokers were 2.13 (95% CI 1.79, 2.53) and 3.04 (95% CI 2.70, 3.42), respectively. In multivariable Cox models, cigarette smoking was associated with gout with a hazard ratio of 0.76 (95% CI 0.59, 0.98) overall, 0.68 (95% CI 0.49, 0.93) among men and 0.92 (95% CI 0.60, 1.41) among women. Lower risk for smokers was evident among all obesity categories, but not among women. Sensitivity analysis suggested that the magnitude of the true odds ratio might be lower than our calculations. CONCLUSION: Cigarette smoking is associated with lower incidence of gout and this is not explained by differences in the prevalence of risk factors. The mechanistic underpinnings of this epidemiological finding merits further study.

Responsiveness and minimally important difference for the patient-reported outcomes measurement information system (PROMIS) 20-item physical functioning short form in a prospective observational study of rheumatoid arthritis.

OBJECTIVE: To estimate responsiveness (sensitivity to change) and minimally important difference (MID) for the Patient-Reported Outcomes Measurement Information System (PROMIS) 20-item physical functioning scale (PROMIS PF-20). METHODS: The PROMIS PF-20, short form 36 (SF-36) physical functioning scale, and Health Assessment Questionnaire (HAQ) were administered at baseline, and 6 and 12 months later to a sample of 451 persons with rheumatoid arthritis. A retrospective change (anchor) item was administered at the 12-month follow-up. We estimated responsiveness between 12 months and baseline, and between 12 months and 6 months using one-way analysis of variance F-statistics. We estimated the MID for the PROMIS PF-20 using prospective change for people reporting getting 'a little better' or 'a little worse' on the anchor item. RESULTS: F-statistics for prospective change on the PROMIS PF-20, SF-36 and HAQ by the anchor item over 12 and 6 months (in parentheses) were 16.64 (14.98), 12.20 (7.92) and 10.36 (12.90), respectively. The MID for the PROMIS PF-20 was 2 points (about 0.20 of an SD). CONCLUSIONS: The PROMIS PF-20 is more responsive than two widely used ('legacy') measures. The MID is a small effect size. The measure can be useful for assessing physical functioning in clinical trials and observational studies.

A short tutorial on item response theory in rheumatology.

OBJECTIVES: The aim is to familiarize physicians and researchers with the most important concepts of item response theory (IRT) and with its usefulness for improving test administration and data collection in health care. Special attention is given to the versatility of its use within the rheumatic field. METHODS: This short tutorial describes the most important basic principles of item response theory, including the underlying assumptions, the model parameters, and the different models that can be applied. Practical applications are discussed to demonstrate the potential utility of IRT within clinical practice. RESULTS: IRT has proven to be useful for the development and evaluation of both clinical measures as well as patient reported outcomes used for measuring health status in observational studies and clinical trials. Promising features of IRT for the future of test administration are the assessment of local reliability and differential item functioning, the cross-cultural validation or equation of instruments, the development of large item banks, and the administration of computerised adaptive tests. These modern techniques have the ability to maximise measurement precision while simultaneously minimise response burden. CONCLUSIONS: IRT provides a theoretical basis for developing alternatives to the existing tools for assessing health outcome measures in rheumatology.

Relative performance of commonly used physical function questionnaires in rheumatoid arthritis and a patient-reported outcomes measurement information system computerized adaptive test.

OBJECTIVE: To evaluate and compare the measurement precision and sensitivity to change of the Health Assessment Questionnaire disability index (HAQ DI), the Short Form 36 physical functioning scale (PF-10), and simulated Patient-Reported Outcomes Measurement Information System (PROMIS) physical function computer adaptive tests (CATs) with 5, 10, and 15 items, using item response theory-based simulation studies. METHODS: The measurement precision of the various physical function instruments was evaluated by calculating root mean square errors (RMSEs) between true physical function levels (latent physical function score) and estimated physical function levels. Measurement precision was evaluated at 9 levels of physical function, with 5,000 simulated response patterns per level. Sensitivity to change was evaluated by the ability of a simple statistical test to detect simulated change scores of small to moderate magnitude (standardized effect sizes 0.20, 0.35, and 0.50). RESULTS: RMSEs were smaller for the PROMIS physical function 15-item CAT (CAT-15) and CAT-10 than for the HAQ DI and PF-10 across all levels of the latent physical function scale. Only marginal improvement in performance was observed for the CAT-15 compared with the CAT-10, and the CAT-5 performed quite similarly to the HAQ DI and PF-10 across most levels of the latent physical function scale. Substantially improved sensitivity to change was observed for the CAT-10 compared with the HAQ DI and PF-10, particularly in detecting moderate effect sizes. CONCLUSION: Clearly higher measurement precision was observed for the PROMIS CAT compared with the HAQ DI and PF-10. Higher reliability also translated into lower sample size requirements for detecting changes in clinical status.

Extending the floor and the ceiling for assessment of physical function.

OBJECTIVE: To improve the assessment of physical function by enhancing precision of physical function assessment as it pertains to subjects at extreme ends of the health continuum (i.e., subjects with extremely poor function ["floor"] or extremely good health ["ceiling"]). METHODS: Under the Patient-Reported Outcomes Measurement Information System (PROMIS) (a National Institutes of Health initiative), we developed new items to assess floor and ceiling physical function in order to supplement the existing item bank. Using item response theory and standard PROMIS methodology, we developed 31 floor items and 31 ceiling items and administered the items during a 12-month prospective, observational study of 737 subjects whose health status was at either extreme. Effect size was calculated and change over time was compared across anchor instruments and across items. Using the observed changes in scores, we back-calculated sample size requirements for the new and comparison measures. RESULTS: We studied 444 subjects who had been diagnosed as having a chronic illness and/or were of old age and 293 generally fit subjects (including athletes in training). Item response theory analyses confirmed that the new floor and ceiling items outperformed reference items (P < 0.001). The estimated post hoc sample size requirements were reduced by a factor of 2-4 for the floor population and a factor of 2 for the ceiling population. CONCLUSION: Extending the range of items by which physical function is measured can substantially improve measurement quality, reduce sample size requirements, and improve research efficiency. The paradigm shift from assessing disability to assessing physical function focuses assessment on the entire spectrum of physical function, signals improvement in the conceptual base of outcome assessment, and may be transformative as medical goals more closely approach societal goals for health.

Aging, not menopause, is associated with higher prevalence of hyperuricemia among older women.

OBJECTIVE: This work aims to study the associations, if any, of hyperuricemia, gout, and menopause status in the US population. METHODS: Using multiyear data from the National Health and Nutrition Examination Survey, we performed unmatched comparisons and one to three age-matched comparisons of women aged 20 to 70 years with and without hyperuricemia (serum urate ≥6 mg/dL). Analyses were performed using survey-weighted multiple logistic regression and conditional logistic regression, respectively. RESULTS: Overall, there were 1,477 women with hyperuricemia. Age and serum urate were significantly correlated. In unmatched analyses (n = 9,573 controls), postmenopausal women were older, were heavier, and had higher prevalence of renal impairment, hypertension, diabetes, and hyperlipidemia. In multivariable regression, after accounting for age, body mass index, glomerular filtration rate, and diuretic use, menopause was associated with hyperuricemia (odds ratio, 1.36; 95% CI, 1.05-1.76; P = 0.002). In corresponding multivariable regression using age-matched data (n = 4,431 controls), the odds ratio for menopause was 0.94 (95% CI, 0.83-1.06). Current use of hormone therapy was not associated with prevalent hyperuricemia in both unmatched and matched analyses. CONCLUSIONS: Age is a better statistical explanation for the higher prevalence of hyperuricemia among older women than menopause status.

Gout in African Americans.

PURPOSE: African Americans have a substantially higher prevalence of risk factors for gout than Caucasians. The aim of the present study was to compare the risk for incident gout among African Americans and Caucasians. METHODS: Incidence rates of physician-diagnosed gout among 11,559 Caucasian men and 931 African American men aged 35 to 57 years and at high cardiovascular risk, observed for 7 years as a part of the Multiple Risk Factor Intervention Trial, were analyzed. Cox regression models were used to account for potential confounding by age, body mass index, diuretic use, hypertension and diabetes status, aspirin and alcohol consumption, and kidney disease. RESULTS: At baseline, after accounting for risk factors, African Americans had a 14% lower prevalence of hyperuricemia than Caucasians. Incidence of gout increased with increasing prevalence of risk factors in both Caucasians and African Americans. Ethnic disparities in incidence rates were most apparent among those without other risk factors for gout. In separate Cox regression models, after accounting for risk factors, African American ethnicity was associated with a hazard ratio of 0.78 (95% confidence interval [CI], 0.66-0.93) for physician-diagnosed gout and 0.88 (95% CI, 0.85-0.90) for incident hyperuricemia. Significant interactions were observed; the association was the strongest (hazard ratio 0.47; 0.37-0.60). These associations were unaffected by addition of serum urate as a covariate or by using alternate case definitions for gout. CONCLUSIONS: After accounting for the higher prevalence of risk factors, African American ethnicity is associated with a significantly lower risk for gout and hyperuricemia compared with Caucasian ethnicity.

Calibration of the PROMIS physical function item bank in Dutch patients with rheumatoid arthritis.

OBJECTIVE: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank in patients with rheumatoid arthritis (RA) and to evaluate cross-cultural measurement equivalence with US general population and RA data. METHODS: Data were collected from RA patients enrolled in the Dutch DREAM registry. An incomplete longitudinal anchored design was used where patients completed all 121 items of the item bank over the course of three waves of data collection. Item responses were fit to a generalized partial credit model adapted for longitudinal data and the item parameters were examined for differential item functioning (DIF) across country, age, and sex. RESULTS: In total, 690 patients participated in the study at time point 1 (T2, N = 489; T3, N = 311). The item bank could be successfully fitted to a generalized partial credit model, with the number of misfitting items falling within acceptable limits. Seven items demonstrated DIF for sex, while 5 items showed DIF for age in the Dutch RA sample. Twenty-five (20%) items were flagged for cross-cultural DIF compared to the US general population. However, the impact of observed DIF on total physical function estimates was negligible. DISCUSSION: The results of this study showed that the PROMIS PF item bank adequately fit a unidimensional IRT model which provides support for applications that require invariant estimates of physical function, such as computer adaptive testing and targeted short forms. More studies are needed to further investigate the cross-cultural applicability of the US-based PROMIS calibration and standardized metric.

Interaction of inflammation, hyperuricemia, and the prevalence of hypertension among adults free of metabolic syndrome: NHANES 2009-2010.

BACKGROUND: Hyperuricemia and markers of inflammation are correlated with the risk for hypertension. Whether hyperuricemia has any impact on the association between C-reactive protein (CRP) and hypertension is not known. METHODS AND RESULTS: We analyzed cross-sectional data from the National Health and Nutrition Examination Survey, 2009-2010, using ordinary least squares and logistic regression models. Those who met the criteria for metabolic syndrome, had self-reported gout, or were <20 years old were excluded. For each 1-SD increase in serum urate, the serum CRP concentration was 20% higher in unadjusted linear regression models and 13% higher in multivariable linear regression models, after accounting for the effects of age, sex, race, socioeconomic and educational strata, renal function, lipids, smoking, and body mass index. In multivariable models adjusting for the same covariates, hyperuricemia was associated with hypertension with an odds ratio of 2.21 (1.71 to 2.85). When analyzed separately, this was observed in men and women. In multivariable analyses of the overall sample, elevated CRP levels were not associated with hypertension. CONCLUSIONS: Among adults free of metabolic syndrome, elevated uric acid, but not elevated CRP, is independently associated with prevalent hypertension.

Body mass index and its correlates in 1,212 ultramarathon runners: baseline findings from the ULTRA study.

BACKGROUND: Little is known about the sociodemographics and lifestyle behaviors of ultramarathon runners, and the effects of these characteristics on body weight and body mass index (BMI). METHODS: We cross-sectionally analyzed baseline data of 1212 ultramarathoners on sociodemographics, lifestyle behaviors and BMI from the initial 12-month enrollment period in a longitudinal observational study. RESULTS: The ultramarathoners were mostly middle-aged men who were more educated, more likely to be in a stable relationship, and more likely to use over-the-counter vitamins/supplements than the general population. They appear to gain less body weight with advancing age than the general population. Factors with the greatest effect on current BMI were BMI at 25 years of age and sex, which explained 48% and 3% of the variance. Negligible, but statistically significant direct relationships, with BMI were observed for age, work hours per week, television watching hours per week, and composite fat consumption frequency score. Negligible, but statistically significant inverse relationships, with BMI were observed for running distance during the prior year, and composite fruit and vegetable consumption frequency score. CONCLUSIONS: While lifestyle decisions were found to impact BMI within this group of ultramarathoners, BMI at age 25 was the strongest predictor of current BMI.

Health and exercise-related medical issues among 1,212 ultramarathon runners: baseline findings from the Ultrarunners Longitudinal TRAcking (ULTRA) Study.

Regular exercise is associated with substantial health benefits; however, little is known about the health impact of extreme levels of exercise. This study examined the prevalence of chronic diseases, health-care utilization, and risk factors for exercise-related injuries among ultramarathon runners. Retrospective, self-reported enrollment data from an ongoing longitudinal observational study of 1,212 active ultramarathon runners were analyzed. The most prevalent chronic medical conditions were allergies/hay fever (25.1%) and exercise-induced asthma (13.0%), but there was a low prevalence of serious medical issues including cancers (4.5%), coronary artery disease (0.7%), seizure disorders (0.7%), diabetes (0.7%), and human immunodeficiency virus (HIV) infection (0.2%). In the year preceding enrollment, most (64.6%) reported an exercise-related injury that resulted in lost training days (median of 14 days), but little nonattendance of work or school due to illness, injury, or exercise-related medical conditions (medians of 0 days for each). The knee was the most common area of exercise-related injury. Prior year incidence of stress fractures was 5.5% with most (44.5%) involving the foot. Ultramarathon runners who sustained exercise-related injuries were younger (p<0.001) and less experienced (p<0.01) than those without injury. Stress fractures were more common (p<0.01) among women than men. We conclude that, compared with the general population, ultramarathon runners appear healthier and report fewer missed work or school days due to illness or injury. Ultramarathon runners have a higher prevalence of asthma and allergies than the general population, and the prevalence of serious medical issues was nontrivial and should be recognized by those providing medical care to these individuals. Ultramarathon runners, compared with shorter distance runners, have a similar annual incidence of exercise-related injuries but higher proportion of stress fractures involving the foot, and it is the younger and less experienced ultramarathoners who appear most at risk for injury.