Classification criteria for systemic sclerosis (SSc) are being updated.
To select a set of items potentially useful for the classification of SSc using consensus procedures including the Delphi and nominal group techniques (NGT).
Items were identified through two independent consensus exercises performed by the Scleroderma Clinical Trials Consortium (SCTC) and the EULAR Scleroderma Trials and Research Group (EUSTAR). The first-round items from both exercises were collated and redundancies were removed leaving 168 items. A 3-round Delphi exercise was performed using a 1–9 scale (1=completely inappropriate and 9=completely appropriate) and a consensus meeting using NGT. During the last Delphi, the items were ranked on a 1–10 scale.
Round 1: 106 experts rated the 168 items. Those with a median score <4 were removed, resulting in a list of 102 items. Round 2: The items were again rated for appropriateness and subjected to a consensus meeting using NGT by European and North American SSc experts (n=16), resulting in 23 items. Round 3: SSc experts (n=26) then individually scored each of the 23 items in a last Delphi round, using an appropriateness score (1–9) and ranking their 10 most appropriate items for classification of SSc. Presence of skin thickening, SSc-specific autoantibodies, abnormal nailfold capillary pattern and Raynaud’s phenomenon ranked highest in the final list that also included items indicating internal organ involvement.
The Delphi exercise and NGT resulted in a set of 23 items for classification of SSc which will be assessed for their discriminative properties in a prospective study.
Delphi technique; nominal group technique; systemic sclerosis; scleroderma; classification; classification criteria
Classification criteria for systemic sclerosis (SSc) are being updated jointly by ACR and EULAR. Potential items for classification were reduced to 23 using Delphi and Nominal Group Techniques. We evaluated the face, discriminant and construct validity of the items to be further studied as potential criteria.
Face validity was evaluated using the frequency of items in patients sampled from the Canadian Scleroderma Research Group, 1000 Faces of Lupus, the Pittsburgh, Toronto, Madrid and Berlin CTD databases. SSc (n=783) were compared to 1071 patients with diseases similar to SSc (mimickers): SLE (n=499), myositis (n=171), Sjögren’s syndrome (n=95), Raynaud’s phenomenon (RP) (n=228), MCTD (n=29), and idiopathic PAH (n=49). Discriminant validity was evaluated using odds ratios (OR). For construct validity, empiric ranking was compared to expert ranking.
Compared to mimickers, SSc are more likely to have skin thickening (OR=427), telangiectasias (OR=91), anti-RNA polymerase III antibody (OR=75), puffy fingers (OR=35), finger flexion contractures (OR=29), tendon/bursal friction rubs (OR=27), anti-topoisomerase-I antibody (OR=25), RP (OR=24), finger tip ulcers/pitting scars (OR=19), anti-centromere antibody(OR=14), abnormal nailfold capillaries (OR=10), GERD symptoms (OR=8), and ANA, calcinosis, dysphagia, esophageal dilation (all OR=6), interstitial lung disease/pulmonary fibrosis (OR=5) and anti-PM-Scl antibody (OR=2). Reduced DLCO, PAH, and reduced FVC had OR<2. Renal crisis and digital pulp loss/acro-osteolysis did not occur in SSc mimickers (OR not estimated). Empiric and expert ranking were correlated (Spearman rho 0.53, p=0.01).
The candidate items have good face, discriminant and construct validity. Further item reduction will be evaluated in prospective SSc and mimicker cases.
Systemic Sclerosis; Scleroderma; Classification Criteria; Validity; Bayesian
To examine the productivity of patients with scleroderma (SSc) both outside and within the home in a large observational cohort.
162 patients completed the Work Productivity Survey. Patients indicated whether or not they were employed outside of the home, how many days/month they missed work (employment or household work) due to SSc and how many days/month productivity was decreased ≥ 50%. Patients also completed other patient-reported outcome measures. We developed binomial regression models to assess the predictors of days missed from work (paid employment or household activities). The covariates included: type of SSc, education, physician and patient global assessments, HAQ-DI, FACIT-Fatigue, and Center of Epidemiologic Studies Depression Scale – Short Form (CESD).
The average age of patients was 51.8 years and 51% had limited SSc. Of 37% patients employed outside of the home, patients reported missing 2.6 days/month of work and had 2.5 days per month productivity reduced by half. Of the 102 patients who were not employed, 39.4% were unable to work due to their SSc. When we assessed patients for household activities (N = 162), patients missed an average of 8 days of housework/month and had productivity reduced by average of 6 days/month. In the regression models, patients with lower education and poor assessment of overall health by physician were more likely to miss work outside the home. Patients with limited SSc and high HAQ-DI were more likely to miss work at home.
SSc has a major impact on productivity at home and at work. Nearly 40% of patients reported disability due to their SSc.
Scleroderma; systemic sclerosis; work productivity survey; work productivity; word disability; epidemiology; FACIT-Fatigue; CESD; CESD-10; HAQ-DI
The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Roadmap initiative is a cooperative group program of research designed to develop, evaluate, and standardize item banks to measure patient-reported outcomes relevant across medical conditions. For adults, 11 domains have been developed in physical, mental, and social health.
The objective of the current study was to assess feasibility and construct validity of PROMIS item banks versus legacy measures in a observational study in systemic sclerosis (SSc).
Patients with SSc in a single academic center completed computerized adaptive technology (CAT) administered PROMIS item banks during the clinic visit and legacy domains (using paper-and-pencil). The construct validity of PROMIS items was evaluated by examining correlations with corresponding legacy measures using multitrait-multimethod analysis.
Participants consisted of 143 SSc patients with an average age of 51.5 years; 71% were female and 68% were Caucasian. The average number of items completed for each CAT-administered item bank ranged from 5 to 8 (69 CAT items per patient), and the average time to complete each CAT-administered item bank ranged from 48 seconds to 1.9 minutes per patient (average time= 11.9 minutes/per patient for 11 banks). All correlations between PROMIS domains and respective legacy measures were large and in the hypothesized direction (ranged from .61 to .82).
Our study supports the construct validity of the CAT-administered PROMIS item banks and shows that they can be administered successfully in a clinic with support staff. Future studies should assess the feasibility of PROMIS item banks in a busy clinical practice
Systemic sclerosis; PROMIS; health-related quality of life; construct validity
T cells, particularly those producing IL-4, are implicated in inflammation-mediated fibrosis. In our phase I/IIa open-label pilot study in 15 patients with scleroderma-interstitial lung disease (SSc-ILD), high-dose imatinib treatment showed modest improvement in lung function and skin score, but with several adverse events. Here, we investigated T cell phenotype and cytokine production in bronchoalveolar lavage (BAL) from patients enrolled in this trial. We found that IL-4+ T cells showed a stronger correlation with ground glass opacity (GGO) than fibrosis scores on lung high-resolution computer tomography scans. Frequencies of IL-4+ T cells also discriminated patients with high (≥20) versus low (<20) GGO scores. Functional annotation clustering of proteins that correlated with T cells identified two major clusters that belonged to immune/inflammatory and wounding response. Repeat analyses after one year of treatment in 10 BAL samples, one each from the right middle and lower lobes of lung from 5 patients, showed that post-imatinib, IL-4+ T cells were profoundly reduced but CD4+ T cells increased, except in one patient who showed worsening of SSc-ILD. Post-imatinib increase in CD4+ T cells correlated with soluble ICAM-3 and PECAM-1 levels in BAL, which associated with the lack of worsening in SSc-ILD. Thus, imatinib might confer its therapeutic effect in fibrosis via re-directing T cell responses from type 2 to other, non-type 2 cytokine producing CD4+ T cells.
IL-4; T cells; imatinib; scleroderma; fibrosis
Transforming growth factor-beta (TGF-b) and platelet-derived growth factor (PDGF) may play a critical role in systemic sclerosis- interstitial lung disease (SSc-ILD) and imatinib is a potent inhibitor of TGF-b and PDGF production. We report a phase I/IIa open-label pilot study of imatinib in patients with SSc-ILD. Our primary aim was to assess imatinib’s safety; we also explored efficacy.
We recruited 20 SSc patients with FVC< 85% predicted, dyspnea on exertion, and presence of ground glass appearance on HRCT. Patients received oral imatinib therapy (up to 600 mg/day) for a period of 1 year. Adverse events, pulmonary function tests, and modified Rodnan skin score (MRSS) were captured every 3 months. The course of lung function, HAQ-DI and MRSS were modeled over the length of study to explore efficacy.
The majority of patients were female (65%), Caucasian (75%) and had diffuse SSc (70%). The baseline mean (SD) FVC%predicted was 65.2 (14.0) and MRSS was 18.7 (10.1). Mean(SD) imatinib dose was 445 (125) mg/day. Of 20 patients, 12 completed the study, 7 discontinued due to adverse events (AEs), and 1 patient was lost to follow-up. Common AEs (≥ 20%) included fatigue, facial/lower extremity edema, nausea and vomiting, diarrhea, generalized rash, and new onset proteinuria. Treatment with imatinib showed a trend towards an improvement of FVC%predicted of 1.74% (p>0.05) and MRSS of 3.9 units (p< 0.001).
Use of high-dose daily (600 mg/day) imatinib in SSc-ILD was associated with a large number of AEs. Our AE experience suggests that doses lower than 600 mg/day imatinib may be appropriate and that further dose ranging is needed to understand the therapeutic index of imatinib in SSc.
imatinib; clinical trial; systemic sclerosis; scleroderma-related lung fibrosis
Guideline or diagnostic criteria in clinical practice assist physicians in their clinical decision-making and improve health outcomes for patients. Diagnostic and classification criteria are based on evidence from rigorously conducted controlled studies. Formal group consensus methods have been developed to organize subjective judgments and to synthesize them with the available evidence. This review discusses four types of formal consensus methods used in the health field and their applications in rheumatology: the Delphi method, nominal group technique, RAND/UCLA Appropriateness Method, and National Institutes of Health consensus development conference.
Patients with scleroderma interstitial lung disease (SSc-ILD) are thought to have the greatest decline in lung function (forced vital capacity % predicted [FVC%]) in the early years after onset of systemic sclerosis (SSc). We assessed the natural history of FVC% decline in patients receiving placebo in the Scleroderma Lung Study and evaluated possible factors for cohort enrichment for future therapeutic trials.
Patients randomized to placebo (N=79) were divided into 3 groups based on SSc disease duration (0–2, 2–4 and >4 years). Descriptive statistics and a mixed effect model were used to analyze the rate of decline of FVC% over a 1-year period. We performed additional analyses stratified by severity of fibrosis on HRCT and explored interactions of severity and disease duration.
The mean (SD) decline in the unadjusted FVC% during the 12-month period was 4.2 (12.8)%. At baseline, 28.5%, 43.0% and 28.5% of patients were in 0–2, 2–4 and >4 years disease groups, respectively. Rate of decline in FVC% was not significantly different across the 3 disease groups (P=0.85). When stratified by baseline fibrosis on HRCT, rate of decline of FVC% was statistically greater in the severe fibrosis group (annualized decline in FVC% in the severe group=7.2 vs. 2.7, p=0.008). The decline in the severe fibrosis group was most pronounced in those with relatively short disease duration (0–2 years, annualized decline= 7.0%).
Patients with SSc-ILD in the Scleroderma Lung Study had similar rates of progression of lung disease irrespective of disease duration. Baseline HRCT fibrosis score is a predictor of future FVC% decline in the absence of effective treatment.
Pulmonary arterial hypertension (PAH) increases mortality in systemic sclerosis (SSc). The multicenter PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) registry prospectively follows SSc subjects at high-risk for, or with incident pulmonary hypertension (PH). Herein, we describe registry design and baseline characteristics of subjects enrolled during the first 18 months since study inception.
High-risk subjects are enrolled and classified as Pre-PAH if they have 1) carbon monoxide diffusing capacity (DLCO) < 55% predicted, 2) % predicted forced vital capacity/DLCO ratio ≥1.6, or 3) an estimated right ventricular systolic pressure > 35 mm Hg on echocardiography. Subjects with right heart catheterization confirmed incident PH (mean pulmonary artery pressure ≥ 25 mm Hg within previous 6 months) are subclassified into PAH, pulmonary venous hypertension secondary to left-sided heart disease (PVH), and PH due to interstitial lung disease (PH-ILD). Baseline and biannual demographic, clinical, and laboratory data as well as patient-reported health questionnaires are collected.
There are 237 subjects enrolled in PHAROS. The majority are Caucasian (73%) and women (87%). There are 166 Pre-PAH and 71 Definite PH subjects (49 PAH, 7 PVH, and 15 PH-ILD).
PHAROS is the largest U.S. and Canadian cohort of SSc subjects at high-risk for or with incident PAH. PAH-specific therapies are approved for 49/71 subjects with RHC-confirmed-PAH. Analyses of PHAROS registry data will permit identification of risk factors for the development of PAH amongst SSc patients at high-risk for PAH and enhance our understanding of the course of SSc-PAH.
Systemic scleroderma; Pulmonary hypertension; Registry; Pulmonary arterial hypertension
The prevalence of gout is increasing, and most research on the associated burden has focused on serum urate (sUA) levels. The present study quantifies the impact of the presence of tophi and frequency of acute gout attacks on health-related quality of life (HRQOL), productivity, and healthcare resource utilization.
Patients with self-reported gout (n = 620; 338 in US and 282 across France, Germany, and UK) were contacted based on inclusion in the 2010 US and EU National Health and Wellness Surveys (Kantar Health) and the Lightspeed Research ailment panel. Respondents were categorized into mutually-exclusive groups based on number of gout flares experienced in the past 12 months (0/don’t recall, 1–2, 3, 4–5, 6+), current presence of tophi (none, 1+, or not sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider visits in the last 6 months, and work productivity and activity impairment (WPAI) were compared across groups.
Most patients were males, mean age of 61 years, who reported experiencing at least one acute gout flare in the past 12 months, and 12.3% (n = 76) reported presence of tophi. Among the 27.7% (n = 172) of patients who were aware of their sUA levels, higher sUA was associated with more flares and tophi. Decreased HRQOL was associated with more frequent flares and presence of tophi. In multivariable models predicting outcomes based on presence of tophi and number of flares, both flares (≥4) and tophi (≥1) were associated with HRQOL decrements on physical and mental component summary scores and health utilities (all p < 0.05), after adjustment for age, gender, and time since diagnosis. Flares were also associated with greater activity impairment.
Impairments associated with gout flares and presence of tophi, across patients in the US and EU, underscore the importance of effective management of this potentially curable condition.
Gout; Quality of life; Productivity; Refractory chronic gout
To provide minimally important difference (MID) estimates for the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) in a longitudinal observational cohort.
We administered the UCLA SCTC GIT 2.0 to 115 patients with SSc at 2 time points 6 months apart. UCLA SCTC GIT 2.0 has 7 multi-item scales: Reflux, Distention/Bloating, Diarrhea, Fecal Soilage, Constipation, Emotional Well-being, and Social Functioning and a Total GIT score. All scales are scored from 0 (better HRQOL) to 3 (worse HRQOL) except the diarrhea and constipation scales (ranges are 0–2 and 0– 2.5, respectively). Patients also rated their overall, upper, and lower GIT involvement during the 2nd visit using a “Much better, somewhat better, almost the same, somewhat worse, or much worse” response scale. The minimally changed group was defined by those reporting they were somewhat better or somewhat worse compared to 1st visit.
Study participants were 84% female and 81% white with a mean disease duration of 6.9 years. The MID estimates for improvement ranged from 0.07 for the Social Functioning scale to 0.36 for Emotional Well-Being scale. For worsening, the MID estimates ranged from 0.06 for Fecal Soilage scale to 0.21 for the Social Functioning Scale.
We provide MID estimates for the UCLA SCTC GIT 2.0 scales. This information can aid in interpreting scale scores in future RCTs and observational studies.
gastrointestinal; scleroderma; systemic sclerosis; UCLA SCTC GIT 2.0; minimally important differences; minimal clinically important differences
To evaluate responses by time to non-biologic DMARD initiation in an early seropositive, DMARD naïve, rheumatoid arthritis (RA) cohort.
Patients and Methods
Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months; range 0.6 to 15.9). Subjects who started their first DMARD within 5 months of symptom onset were compared to subjects who started after 5 months. Disease activity scores (DAS-44) and total Sharp Score (TSS) progression rates were analyzed using Wilcoxon rank-sum and Chi-square tests; multiple linear regression analysis adjusted for potential covariates. The slope of the least-squares regression line was calculated to estimate the annualized TSS progression rates.
Of 233 RA patients, 76% were female, mean age was 50 (SD 13).
At DMARD start, DAS-44 was similar in all subsets within the 0.6 to 15 months duration between symptom onset and DMARDS initiation. Erosion scores tended to be higher in those who started DMARD later, but HAQ scores were higher in those who started DMARD earlier During the 2 years after DMARD initiation, improvements in HAQ and DAS-44 were similar in the various duration subsets with about 25% ever achieving DAS remission (<1.6). Radiographic progression tended to be numerically but not statistically more rapid in the earlier subsets.
Following initiation of non-biologic DMARD therapy at various times within 15 months of symptom onset, improvements of DAS-44, HAQ-DI, remission rate and radiographic progression rate were similar, although higher baseline erosion scores were present in those with later DMARD initiation.
Rheumatoid arthritis; DMARDS; Window of opportunity; DAS; Radiograph; Remission
Anti-U3-RNP or anti-fibrillarin antibodies (AFA) are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. The current study examines the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc.
Overall, 278 AA SSc patients and 328 unaffected AA controls were enrolled from three North American cohorts. Clinical features, autoantibody profile, and HLA-class-II genotyping were captured. To compare the clinical manifestations, relevant clinical features were adjusted for disease duration. The Cox proportional hazards regression was used to determine the effect of AFA on survival.
Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR=11.5, p<0.0001) and AFA negative SSc patients (OR=5.2, p=0.0002). AFA positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger Perivascular and lower Lung Severity Indices (p=0.004, p=0.014, p=0.019, p=0.092, p=0.006, and p=0.016, respectively). After adjustment for age at enrollment, AFA positive patients did not have different survival compared with patients without AFA (p=0.493).
These findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. Moreover, AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis, and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. However, presence of AFA did not change survival.
Scleroderma; GENISOS; anti-U3-RNP; digital ulcer; HLA DRB1; and Scleroderma Family Registry
Objective. Rheumatologic disorders are associated with sleep disturbances. This study examines sleep disturbance correlates in patients with SSc.
Methods. Participants are 180 SSc patients in an observational study. At baseline, patients completed the Medical Outcomes Study Sleep measure (MOS-Sleep scale). In addition, patients were administered other patient-reported outcome (PRO) measures including the 36-item short form (SF-36), HAQ disability index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Center for Epidemiologic Studies Depression (CESD) scale and a University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Questionnaire (UCLA SCTC GIT 2.0). Descriptive statistics were assessed for six scales of MOS-Sleep and the 9-item sleep problem index (SLP-9; a composite index). We computed Spearman’s rank-order correlations between the MOS-Sleep scales and the HAQ-DI, FACIT-Fatigue, CESD, SSc-SCTC GIT 2.0 and SF-36 scales. In addition, we developed a regression model to assess predictors of SLP-9 scores. Covariates included demographics, physician variables of disease severity and patient-reported variables of worsening symptoms and the PRO measures.
Results. SSc patients reported a mean (s.d.) of 7.1 (1.73) h of sleep a night. Patients reported worse scores on four of six scales (except for snoring and sleep quantity) compared with the US general population (P < 0.001). SLP-9 was correlated with worsening pain and dyspnoea over the past 1 month, reflux scale of the UCLA SCTC GIT 2.0, CESD and FACIT-Fatigue (ρ 0.26–0.56). In the stepwise multivariate regression model, the CESD, worsening dyspnoea and reflux scale were significantly associated with SLP-9 index.
Conclusion. Sleep disturbances are common in SSc and are associated with worsening dyspnoea, depressed mood and severity of reflux symptoms.
Systemic sclerosis; Scleroderma; Sleep; Depression; Gastroesophageal reflux; Quality of life; SF-36; HAQ disability index (HAQ-DI); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue); Center for Epidemiologic Studies Depression (CESD) scale; University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Questionnaire (UCLA SCTC GIT 2.0)
Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk for atherosclerosis and cardiovascular disease. Our objective was to perform a systematic review and meta-analysis to determine if atherosclerosis is increased in patients with SSc compared to healthy individuals.
We performed a systematic search of studies published in PubMed and the Cochrane database up to May 2010, and reviewed recently-published abstracts. Two reviewers independently screened articles to identify studies comparing rates of atherosclerosis in SSc patients vs. healthy controls using one of the following modalities: angiography, doppler ultrasound to assess plaque and carotid intima-medial thickness (CIMT), computer tomography, magnetic resonance imaging, flow mediated dilation (FMD), ankle-brachial index, or autopsy findings. For CIMT and FMD, we computed a pooled estimate of the summary mean difference (MD) and explored predictors of CIMT using random-effects meta-regression.
Of 3,156 articles initially identified, 33 were selected for the systematic review. Meta-analysis included 14 CIMT and 7 FMD studies. Compared to healthy controls, SSc patients had higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed SSc subjects had increased CIMT [MD 0.11mm (95% CI 0.05, 0.17), P=0.0006] and lower FMD [MD -3.07% (95%CI -5.44, -0.69), P=0.01]. There was marked heterogeneity between the studies, namely from variations in disease duration and difference in mean/median age between SSc and control groups.
Patients with SSc have increased atherosclerosis compared to healthy controls. Further studies should elucidate the mechanism of this increased risk.
Objective. The Gout Impact Scale (GIS) is a gout-specific quality of life instrument that assesses impact of gout during an attack and impact of overall gout. The GIS has five scales and each is scored from 0 to 100 (worse health). Our objective was to assess minimally important differences (MIDs) for the GIS administered in a randomized controlled trial (RCT) assessing rilonacept vs placebo for prevention of gout flares during initiation of allopurinol therapy.
Methods. Trial subjects ( n = 83) included those with two or more gout flares (self-reported) in the past year. Of these, 73 had data for Weeks 8 vs 4 and formed the MID analysis group and were analysed irrespective of the treatment assignment. Subjects completed the GIS and seven patient-reported anchors. Subjects with a one-step change (e.g. from very poor to poor) were considered as the MID group for each anchor. The mean change in GIS scores and effect size (ES) was calculated for each anchor’s MID group. The average of these created the overall summary MID statistics for each GIS. An ES of 0.2–0.5 was considered to represent MID estimates.
Results. Trial subjects (n = 73) were males (96.0%), White (90.4%), with mean age of 50.5 years and serum uric acid of 9.0 mg/dl. The mean change score for the MID improvement group for scales ranged from −5.24 to −7.61 (0–100 scale). The ES for the MID improvement group for the four scales ranged from 0.22 to 0.38.
Conclusion. The MID estimates for GIS scales are between 5 and 8 points (0–100 scale). This information can aid in interpreting the GIS results in future gout RCTs.
Trial Registration. Clinicaltrials.gov, www.clinicaltrials.gov, NCT00610363.
Gout assessment questionnaire; Gout impact scale; Minimally important difference; Minimal clinically important differences; Rilonacept; Clinical trial design; Health-related quality of life; Health status
Objective. Short Form-36 (SF-36) is a validated outcome measure to assess health-related quality of life (HRQOL) in patients with gout. We assessed responsiveness to change of SF-36 in patients with gout.
Methods. SF-36 was administered at baseline and at yearly intervals. We assessed the minimal clinically important differences (MCIDs) at the first and second year. We also assessed the responsiveness to change (effect size) and interpreted it based on Cohen’s criteria. We modelled the improvement (defined as ≥MCID) in SF-36 scales and summary scores. Covariates included age, presence of tophi, comorbidities, baseline joint involvement, baseline serum urate, change in serum urate and the number of flares from baseline to 12 months.
Results. Of 99 subjects, 96 were male, mean age was 57.1 years, disease duration was 8.2 years and 40.4% had tophi. Ninety-two patients were treated with urate-lowering therapy (ULT) and daily colchicine, and seven were only on colchicine. Baseline mean serum urate level was 8.9 mg/dl and mean number of flares was 4.7 over last year. ULTs were associated with reduction in serum uric acid and number of flares (P < 0.001 for both) over 12 months. Therapy was associated with 22–70% of the patients achieving MCID in SF-36 scores at 12 months. Effect size estimates ranged from negligible to large (SF-36 mental component summary 0.08–bodily pain 1.09). Reduction in flares independently predicted improvements in three SF-36 physical scales (P = 0.001–0.06). Improvement in SF-36 scores was maintained at 2 years.
Conclusion. In our real-life observational cohort, chronic urate lowering therapy and colchicine was associated with clinically meaningful improvements in HRQOL at 1 year and then maintained at 2 years. SF-36, especially physical domains and physical component summary, are responsive to change in gout.
Gout; Health-related quality of life; Quality of life; Flares; Urate-lowering therapy; Minimal clinically important differences; Minimally important differences; Short Form-36, Gout prophylaxis
With remission in rheumatoid arthritis (RA) an increasingly attainable goal, there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome in clinical trials.
A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism and the Outcome Measures in Rheumatology Initiative (OMERACT) met to guide the process and review prespecified analyses from clinical trials of patients with RA. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures to define remission including at least joint counts and an acute phase reactant. Members were surveyed to select the level of each core set measure consistent with remission. Candidate definitions of remission were tested including those that constituted a number of individual measures in remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient reported outcomes and the ability of candidate measures to predict later good x-ray and functional outcomes.
Survey results for the definition of remission pointed to indexes at published thresholds and to a count of core set measures with each measure scored as 1 or less (e.g. tender and swollen joint counts, CRP and global assessments on 0-10 scale). Analyses suggested the need to include a patient reported measure. Examination of 2 year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good x-ray and functional outcomes, although DAS28 based measures of remission did not predict good radiographic outcomes as well as did the other candidate definitions. Given these and other considerations, we propose that a patient be defined as in remission based on one of two definitions : 1: When their scores on the following measures are all <1: tender joint count, swollen joint count, CRP (in mg/dL) and patient global assessment (0-10 scale), OR 2: when their score on the SDAI is < 3.3.
We propose two new definitions of remission both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected in each trial as an outcome and that the results on both be reported in each trial.
Objectives. SSc-associated gastrointestinal tract involvement (SSc-GIT) is an important predictor of depressive symptoms. University of California at Los Angeles Scleroderma Clinical trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) is a 34-item valid instrument that captures GIT symptom severity and impact on quality of life. It has seven GI-specific scales and a total GIT score. The objectives were to assess: (i) whether there is an association between depressed mood with GI symptom scales as assessed by the UCLA SCTC GIT 2.0 instrument; and (ii) to explore which GI-specific symptom scales are associated with depressed mood in patients with SSc.
Methods. One hundred and fifty-two patients with SSc completed the UCLA SCTC GIT 2.0 and the Center for Epidemiologic Studies Short Depression scale (CES-D10). Patients were divided into depressed (CES-D ≥ 10) or non-depressed group (CES-D < 10) and compared using t-test or chi-square test. Multiple linear regression was used to determine associations between GI scales and depressed mood (CES-D).
Results. Study participants were 84% female, 78% Caucasian and 40% had depressed mood (CES-D10 ≥ 10). Patients with depressed mood had statistically worse GI scale scores (except fecal soilage) and worse total GIT score (P < 0.05). In the multivariable model reflux and constipation scales were independently associated with worse CES-D scores (P = 0.01–0.06)
Conclusion. SSc-GIT involvement is associated with depressed mood. Reflux and constipation scales of UCLA-SCTC GIT 2.0 were independently associated with CES-D. Future studies should assess if treatment of GIT symptoms will improve depressed mood in patients with SSc-GIT.
Scleroderma; Systemic sclerosis; Depression; Center for Epidemiologic Studies Short Depression scale; Gastrointestinal involvement; Reflux; Constipation; University of California at Los Angeles Scleroderma Clinical trial Consortium Gastrointestinal Tract 2.0
Objective. Although the incidence of dcSSc is higher in African-American and Hispanic populations compared with European Caucasian patients, it is not clear whether there are differences in subsequent disease course. Also, the potential impact of gender on the disease course of dcSSc is not well defined. Our objective was to assess the course of modified Rodnan skin score (MRSS), HAQ-disability index (HAQ-DI) and forced vital capacity per cent (FVC%) predicted between men vs women and three ethnic groups with dcSSc participating in three randomized clinical trials (RCTs).
Method. Data from RCTs (n = 495) were pooled and analysed. Baseline characteristics were compared in men vs women and among ethnic groups. A linear mixed effects model was used to assess the predictors of MRSS, HAQ-DI and FVC%. The primary independent variables were time-in-study and its interaction with gender and ethnicity. The models were adjusted for other covariates that were significant at baseline between gender and ethnicity analyses.
Results. Men had lower HAQI-DI scores compared with women (P < 0.05). Among the three ethnic groups, Caucasians were older, African-Americans had lower FVC% predicted and Hispanics had greater tender joint counts (P < 0.05). The course of MRSS, HAQ-DI and FVC% predicted during the study period was not significantly different between gender and three ethnicities. Time-in-study was an independent predictor of improvement in MRSS and HAQ-DI.
Conclusion. Our analysis explores the influence of gender and ethnicity on disease course in RCTs. These findings are relevant to issues of future trial design.
Scleroderma; Randomized clinical trial; Clinical trials; Systemic sclerosis; Gender; Race; Ethnicity; Diffuse cutaneous systemic sclerosis
To evaluate changes in vascular and musculoskeletal involvement in subjects in the Scleroderma Lung Study (SLS), a multicenter, double-blind, randomized, controlled trial comparing placebo treatment to oral cyclophosphamide for 1 year in systemic sclerosis (SSc) patients with interstitial lung disease. Subjects were then followed off study agent for an additional 12 months.
The following parameters were noted at baseline and every 6 months for each patient: digital tip ulcers, other dermal ulcers, joint swelling, joint tenderness, large joint contractures, muscle tenderness, muscle weakness, oral aperture, hand extension, and fist closure.
158 patients were enrolled from 13 centers in the United States; 79 were randomized to the cyclophosphamide group (CYC) and 79 to the placebo group. There were no differences in dermal ulcer and musculoskeletal measures between CYC and placebo groups at baseline, 12, and 24 months. Improvement in FVC % predicted was associated with improvement in Rodnan skin score (P<0.05) at 12 and 24 months, and with increased mean oral aperature at 24 months (P=0.005).
These data document the frequency and course of these vascular and musculoskeletal features over time, thus providing essential information for sample size calculations and magnitude of effect in future clinical trials. There was no treatment effect of cyclophosphamide on the vascular and musculoskeletal features described.
Scleroderma; musculoskeletal; joints; vascular; randomized controlled trial; cyclophosphamide
Lung involvement is the leading cause of death in systemic sclerosis (SSc), however lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF).
We retrospectively evaluated bilateral LT recipients (LTR) with SSc or IPF at our center between 1/1/2003 and 12/31/2007. The primary endpoint was all-cause mortality at 1 year post-LT. Secondary endpoints included assessments of acute rejection (AR), pulmonary function, infection, and chronic rejection.
14 patients with SSc and 38 patients with IPF underwent LT. Apart from a younger SSc cohort (53.2 vs. 58.8 years, p=0.02), the two groups were well matched. One year all-cause mortality was no different between SSc (6.6%) and IPF (13.1%) groups, after adjusting for age (p=0.62). Rates of AR ≥ 2 were significantly increased for the SSc compared to the IPF group (HR 2.91; p=0.007). Other endpoints including chronic rejection, infection, and pulmonary function showed no differences.
SSc LTR experience similar survival 1 year post-LT when compared to IPF. AR rates may be significantly higher in the SSc group. Longer follow-up is necessary to determine the effects of gastrointestinal dysfunction and AR on late allograft function in SSc LTR.
lung transplantation; systemic sclerosis
Systemic sclerosis (SSc), primary pulmonary hypertension (PPH), and sickle cell disease (SCD) are uncommon vasculopathic diseases affecting women. We estimated the nationwide occurrence of pregnancies in women with these conditions and compared pregnancy outcomes to the general obstetric population.
We studied the 2002–2004 Nationwide Inpatient Sample (NIS), of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations and deliveries among women with SSc, PPH, SCD, and the general population. Pregnancy outcomes included length of hospital stay (LOS), hypertensive disorders including preeclampsia (HTN), intrauterine growth restriction (IUGR), and cesarean delivery. Multivariable regression analyses were performed using maternal age, race/ethnicity, antiphospholipid antibody syndrome, diabetes mellitus, and renal failure as covariates.
Of an estimated 11.2 million deliveries, 504 occurred in women with SSc, 182 with PPH, and 4,352 with SCD. SSc was associated with an increased risk of HTN (OR 3.71, 95%CI 2.25–6.15), IUGR (OR 3.74, 95%CI 1.51–9.28), and increased LOS. PPH was associated with an increase in the odds of antenatal hospitalization (OR 4.67, 95%CI 2.88–7.57), HTN (OR5.62, 95%CI 2.60–12.15) and a substantial increase in LOS. SCD was associated with an increased odds of antenatal hospitalization (OR 5.55, 95%CI 5.08–6.09), HTN (OR 1.78, 95%CI 1.48–2.14), and IUGR (OR 2.91, 95% CI 2.16–3.93), with a modest increase in LOS.
Women with SSc, PPH, and SCD have significantly increased rates of adverse pregnancy outcomes, requiring extensive preconceptional counseling about the risks of pregnancy. All pregnancies should be monitored closely for the development of complications.
Pregnancy; sickle cell disease; systemic sclerosis; pulmonary hypertension; outcomes; hospitalization
Arthritis is the leading cause of disability in the United States. We assess the generic health-related quality-of-life (HRQOL) among a nationally representative sample of US adults with and without self-reported arthritis.
The NHMS, a cross-sectional survey of 3844 adults (35–89 years) administered EuroQol-5D (EQ-5D), Health Utilities Index Mark 2 (HUI2) and 3 (HUI3), SF-36v2™, Quality of Well-being Scale self-administered form (QWB-SA), and the Health and Activities Limitations index (HALex) to each respondent via a telephone interview. Weighted multiple linear regression was used to generate age-gender-arthritis stratified unadjusted HRQOL means and means adjusted for sociodemographic, socioeconomic covariates and co-morbidities by arthritis-age category.
The estimated population prevalence of self-reported arthritis was 31%. People with arthritis were more likely to be female, older, of lower socioeconomic status, and had more self-reported comorbidities than were those not reporting arthritis. Adults with arthritis had lower HRQOL on six different indexes compared to adults without arthritis, , with overall differences ranging from 0.03 (QWB-SA, age group 65–74), to 0.17 (HUI3, age group 35–44; all p-value < .05),.
Arthritis in adults is associated with poorer HRQOL. We provide age-related reference values for six generic HRQOL measures in people with arthritis.