The American English version of the validated French Flare Assessment in RA Questionnaire (FLARE-RA).

OBJECTIVE: To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status. METHODS: Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories. RESULTS: Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p < 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p < 0.0001) and with CDAI (corr = 0.45, p < 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07). CONCLUSION: The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).

Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis.

BACKGROUND AND AIMS: To evaluate changes in the high-density lipoprotein (HDL) proteome and HDL function in active rheumatoid arthritis (RA) patients initiating therapy with abatacept or adalimumab in the Abatacept Versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) study. METHODS: Ultra high-pressure liquid chromatography (UHPLC) coupled with ion mobility mass spectrometry (LC-IM-MS) was used to analyze proteins associated with immunoaffinity-captured HDL from plasma of 30 patients with RA randomized to either abatacept (n = 15) or adalimumab (n = 15) therapy. Paraoxonase 1 (PON1) activity, HDL anti-oxidant capacity, cholesterol profiles, and homocysteine levels were also measured at baseline and following treatment. Repeated-measures analyses were performed using mixed-effect linear models to model the within-subject covariance over time. RESULTS: In models controlling for age, sex and treatment group, improvement in inflammation measured by decreases in CRP was associated with improvement in HDL function and changes in several HDL-associated proteins including significant decreases in lipopolysaccharide-binding protein, serum amyloid A-I (SAA-I) and inter-alpha-trypsin inhibitor heavy chain H4 (p values < 0.05). Improvement in disease activity was also associated with changes in multiple HDL-associated proteins. Adalimumab was associated with higher PON1 activity, HDL-associated serotransferrin, and HDL-associated immunoglobulin J chain, and lower HDL-associated SAA-I over time compared with abatacept. CONCLUSIONS: Improvement in inflammation associated with treatment of RA, using either abatacept or adalimumab in the AMPLE study, was associated with improvement in HDL function and significant alterations in the HDL proteome, including proteins involved in the immune response, proteinase inhibition, and lipid metabolism.

Differences in presentation of younger and older systemic sclerosis patients in clinical trials.

OBJECTIVES: To compare the characteristics of younger and older subjects with diffuse cutaneous systemic sclerosis (SSc) entering clinical trials. METHODS: Subjects were participants in three randomised interventional trials that shared relative uniformity of demographics and disease characteristics. Only subjects with diffuse cutaneous systemic sclerosis were evaluated. To maximise possible differences, the lowest (age<38 years) and highest quartiles (age>53 years) were used, and a total of 264 diffuse cutaneous SSc (dcSSc) subjects were identified. For the comparison between the two age groups, generalised linear mixed or linear models with adjustment for population norms, demographics and medications were employed to assess differences attributable to subject age. RESULTS: After adjustment for population norms and study effects, differences in diastolic blood pressure, alkaline phosphatase, AST, and creatinine phosphokinase (CK) were found between the two age groups. After further adjustment for demographics, disease duration and medications, older SSc patients still had significantly higher alkaline phosphatase (11 U/L higher), and lower CK (76 U/L lower) than younger patients (p<0.003 for all). All other variables were not significantly different in the two age groups. CONCLUSIONS: Clinical baseline differences exist between younger and older patients with SSc. However, after adjustment for population norms and potential confounders, including medications, only differences in alkaline phosphatise (only 11U/L) and CK (76 U/L) remain. Overall, older patients with SSc in clinical trials seem to be more similar to younger patients than was previously thought.

Prevalence of low hemoglobin levels and associations with other disease parameters in rheumatoid arthritis patients: evidence from the CORRONA registry.

OBJECTIVE: To estimate the prevalence of low hemoglobin (Hb) levels in a large US cohort of patients with rheumatoid arthritis (RA) and examine the relationship between Hb levels and RA severity, associated comorbidities, and quality-of-life parameters by cross-sectional analysis of data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: The study population comprised patients with RA >18 years of age and clinical information recorded in the CORRONA registry between October 1, 2001 and February 1, 2007. Patients were separated into low (Hb <13 g/dl for men; <12 g/dl for women) and normal Hb groups (Hb >13 g/dl for men; >12 g/dl for women). Hb levels were calculated from recorded hematocrit values. RESULTS: Of the 10,397 study patients, 1734 (16.7%) had low Hb levels and 8663 (83.3%) had normal Hb levels. More patients in the low Hb group had a history of comorbid cardiovascular disease, diabetes, and gastrointestinal disease. The low Hb group exhibited greater disease severity and activity (p<0.05) as reported by patients and rheumatologists. In multivariate analyses, RA severity ([odds ratio] OR 1.24; 95% confidence interval [CI]: 1.07-1.44) and ESR (OR 1.04; 95% CI: 1.03-1.05), and comorbid bleeding ulcers (OR 2.04; 95% CI: 1.01-4.12) were predictive of low Hb levels. CONCLUSION: Despite changes in treatment paradigms, low Hb levels remain prevalent in RA patients. This analysis suggests that low Hb levels may be associated with RA disease severity and the presence of certain comorbidities.

ACR remission criteria and response criteria.

As additional DMARDs have been added to the armamentarium of rheumatologists over the last 60 years, the approach to the treatment of rheumatoid arthritis has changed. Many clinical studies now are geared toward evaluating the concept of eradicating inflammation as a method to seek the elusive goal of sustained remission in RA. One of the first descriptions of remission in 'RA' was by Short et al in 1948, when he documented the natural progression of the disease. Since that time, various criteria have been developed to define RA remission utilizing clinical, radiographic, and laboratory measures. The most stringent of criteria is the American College of Rheumatology Remission Criteria, developed in 1980, which consists of clinical symptoms and signs of inflammation including fatigue, joint pain, morning stiffness, joint tenderness, joint swelling, and erythrocyte sedimentation rate (ESR). Several reports have compared ACR remission criteria to Disease Activity Score (DAS) values to identify equivalent DAS remission values, and these have been extrapolated to modified versions of the DAS, the Simple Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). The ACR remission criteria and the response measures were not designed for use as the target or goal for the clinical management of individual RA patients in routine clinical practice. Nevertheless, rheumatologists yearn for the eradication of inflammation in all RA patients, and attaining remission may be achievable in the future.