Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial

Objective

To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA).

Methods

Post hoc analyses were performed in patients from the PREMIER trial with early RA undergoing 2 years of adalimumab (ADA), methotrexate (MTX), or ADA + MTX combination therapy. Low disease activity was defined as a score <3.2 on the 28‐joint Disease Activity Score using the C‐reactive protein level (DAS28‐CRP), and clinical response by the American College of Rheumatology criteria for 20% improvement at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex‐specific World Health Organization criteria, were analyzed in mixed‐effects models for longitudinal data in men and women as predictors of progressive joint damage, as measured by the modified total Sharp/van der Heijde score (ΔSHS). Data were adjusted for treatment and other patient characteristics, including the DAS28‐CRP.

Results

Baseline hemoglobin was inversely associated with ΔSHS in adjusted analyses (P < 0.05 for both sexes). Baseline anemia predicted greater ΔSHS in MTX‐treated patients over 104 weeks, and in ADA‐ and combination‐treated patients over 26 weeks. Lower hemoglobin concentrations over time, as well as time with anemia, were associated with greater damage progression (P < 0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity.

Conclusion

Low hemoglobin is a DAS28‐CRP‐independent predictor of radiographic joint damage progression in MTX‐treated patients with early RA. This effect decreases over time in ADA‐ and combination‐treated patients, and in clinical responders irrespective of treatment modality.

     

Tele‐Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Objective

To test the effect of patient‐reported outcome (PRO)–based tele‐health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele‐health followup performed by rheumatologists or rheumatology nurses.

Methods

A total of 294 patients were randomized (1:1:1) to either PRO‐based tele‐health followup carried out by a nurse (PRO‐TN) or a rheumatologist (PRO‐TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self‐efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent‐to‐treat (ITT), and multivariate imputation analysis.

Results

Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO‐TR versus control were ?0.10 (90% confidence interval [90% CI] ?0.30, 0.13) and ?0.19 (90% CI ?0.41, 0.02) between PRO‐TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO‐TN had mean ± SD 1.72 ± 1.03 visits/year, PRO‐TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Conclusion

Among RA patients with low disease activity or remission, a PRO‐based tele‐health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

     

Effect of Fatigue,Older Age,Higher Body Mass Index,and Female Sex on Disability in Early Rheumatoid Arthritis in the Treatment‐to‐Target Era

Objective

To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat‐to‐target therapy and identify predictors of adverse outcome.

Methods

The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step‐up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression.

Results

The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON.

Conclusion

Treat‐to‐target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation.

     

Overweight,Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study

Objective

Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis.

Methods

Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline‐based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C‐reactive protein level, and initial treatment.

Results

Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58–0.98]) and obese patients (HR 0.53 [95% CI 0.39–0.71]) were significantly less likely to achieve sREM.

Conclusion

Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease‐modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.

     

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.

     

Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthritis

Objective

The C‐reactive protein (CRP ) level and erythrocyte sedimentation rate (ESR ) are important disease activity biomarkers in rheumatoid arthritis (RA ). This study aimed to determine to what extent obesity biases these biomarkers.

Methods

Body mass index (BMI ) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross‐sectional Body Composition (BC ) cohort (n = 451), including whole‐body dual x‐ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA ) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey.

Results

Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m² versus 20–25 kg/m²). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA ), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA , lower BMI was associated with higher CRP levels and ESR , contrasting with positive associations among men in the general population.

Conclusion

Obesity is associated with higher CRP levels and ESR in women with RA . This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA ; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.

     

Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population‐Based Case–Control Study

Objective

Environmental factors are of importance for the etiology of rheumatoid arthritis (RA), but much remains unknown concerning the contributions from distinct occupational hazards. We explored the association between occupation and the risk of anti–citrullinated protein antibody (ACPA)+ RA or ACPA? RA.

Methods

We analyzed 3,522 cases and 5,580 controls from the Swedish population–based Epidemiological Investigation of Rheumatoid Arthritis case–control study. A questionnaire was used to obtain information on work history and lifestyle factors. Blood samples were drawn for serologic analyses. Unconditional logistic regression was used to calculate the odds ratio (OR) of RA associated with the last occupation before study inclusion. Analyses were performed with adjustments for known environmental exposures and lifestyle factors, including pack‐years of cigarette smoking, alcohol use, body mass index, and education.

Results

Among men, bricklayers and concrete workers (OR 2.9, 95% confidence interval [95% CI] 1.4–5.7), material handling operators (OR 2.4, 95% CI 1.3–4.4), and electrical and electronics workers (OR 2.1, 95% CI 1.1–3.8) had an increased risk of ACPA+ RA. For ACPA? RA, bricklayers and concrete workers (OR 2.4, 95% CI 1.0–5.7) and electrical and electronics workers (OR 2.6, 95% CI 1.3–5.0) had an increased risk. Among women, assistant nurses and attendants had a moderately increased risk of ACPA+ RA (OR 1.3, 95% CI 1.1–1.6). No occupations were significantly associated with ACPA? RA among women.

Conclusion

Mainly occupations related to potential noxious airborne agents were associated with an increased risk of ACPA+ or ACPA? RA, after adjustments for previously known confounders.

     

Suppressing Inflammation in Rheumatoid Arthritis: Does Patient Global Assessment Blur the Target? A Practice‐Based Call for a Paradigm Change

Objective

In current management paradigms of rheumatoid arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role.

Methods

This was a cross‐sectional, single‐center study including consecutive ambulatory RA patients. Data collection comprised swollen 28‐joint count (SJC28), tender 28‐joint count (TJC28), C‐reactive protein (CRP) level, PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorized using American College of Rheumatology/European League Against Rheumatism Boolean‐based criteria: remission, near‐remission (only PGA >1), and nonremission. A binary definition without PGA (3v‐remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state.

Results

A total of 309 patients were included (remission 9.4%, near‐remission 37.2%, and nonremission 53.4%). Patients in near‐remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in nonremission. In multivariable analyses, PGA in near‐remission was explained (R²_adjusted = 0.50) by fatigue, pain, anxiety, and function. Fatigue and pain had no relationship with disease activity measures.

Conclusion

In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP level ≤1) does not equate to low disease impact: a large proportion of these patients are considered in nonremission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This consideration suggests that clinical practice should be guided by 2 separate remission targets: inflammation (3v‐remission) and disease impact.

     

Medical Care Costs Associated With Rheumatoid Arthritis in the US: A Systematic Literature Review and Meta‐Analysis

Objective

Rheumatoid arthritis (RA) is a morbid, mortal, and costly condition without a cure. Treatments for RA have expanded over the last 2 decades, and direct medical costs may differ by types of treatments. There has not been a systematic literature review since the introduction of new RA treatments, including biologic disease‐modifying antirheumatic drugs (bDMARDs).

Methods

We conducted a systematic literature review with meta‐analysis of direct medical costs associated with RA patients cared for in the US since the marketing of the first bDMARD. Standard search strategies and sources were used, and data were extracted independently by 2 reviewers. The methods and quality of included studies were assessed. Total direct medical costs as well as RA‐specific costs were calculated using random‐effects meta‐analysis. Subgroups of interest included Medicare patients and those using bDMARDs.

Results

We found 541 potentially relevant studies, and 12 articles met the selection criteria. The quality of studies varied: one‐third were poor, one‐third were fair, and one‐third were good. Total direct medical costs were estimated at $12,509 (95% confidence interval [95% CI] 7,451–21,001) for all RA patients using any treatment regimen and $36,053 (95% CI 32,138–40,445) for bDMARD users. RA‐specific costs were $3,723 (95% CI 2,408–5,762) for all RA patients using any treatment regimen and $20,262 (95% CI 17,480–23,487) for bDMARD users.

Conclusion

The total and disease‐specific direct medical costs for patients with RA is substantial. Among bDMARD users, the cost of RA care is more than half of all direct medical costs.

     

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics,Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial

Objective

To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.

Methods

We performed a randomized controlled trial among first‐degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE‐RA) group received the web‐based PRE‐RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans‐theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk–related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post‐intervention. Subjects reported behavior change at each visit. We performed intent‐to‐treat analyses using generalized estimating equations for the binary outcome.

Results

Subjects randomized to PRE‐RA were more likely to increase ladder scores over post‐intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE‐RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age‐adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE‐RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).

Conclusion

Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk–related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA‐related autoantibody production or RA development.

     

Effects of a Web‐Based Patient Decision Aid on Biologic and Small‐Molecule Agents for Rheumatoid Arthritis: Results From a Proof‐of‐Concept Study

Objective

To assess the extent to which ANSWER‐2, an interactive online patient decision aid, reduces patients’ decisional conflict and improves their medication‐related knowledge and self‐management capacity.

Methods

We used a pre–post study design. Eligible participants had a diagnosis of rheumatoid arthritis (RA), had been recommended to start using a biologic agent or small‐molecule agent or to switch to a new one, and had internet access. Access to ANSWER‐2 was provided immediately after enrollment. Outcome measures included 1) the Decisional Conflict Scale (DCS), 2) the Medication Education Impact Questionnaire (MeiQ), and 3) the Partners in Health Scale (PIHS). A paired t‐test was used to assess differences pre‐ and postintervention.

Results

The majority of the 50 participants were women (n = 40), and the mean ± SD age of participants was 49.6 ± 12.2 years. The median disease duration was 5 years (25th, 75th percentile: 2, 10 years). The mean ± SD DCS score was 45.9 ± 25.1 preintervention and 25.1 ± 21.8 postintervention (mean change of ?21.2 of 100 [95% confidence interval (95% CI) ?28.1, ?14.4], P < 0.001). Before using ANSWER‐2, 20% of participants had a DCS score of <25, compared to 52% of participants after the intervention. Similar results were observed in the PIHS (mean ± SD 25.3 ± 14.8 preintervention and 20.4 ± 13.0 postintervention; mean change of ?3.7 of 88 [95% CI ?6.3, ?1.0], P = 0.009). Findings from the MeiQ were mixed, with statistically significant differences found only in the self‐management subscales.

Conclusion

Patients’ decisional conflict decreased and perceived self‐management capacity improved after using ANSWER‐2. Future research comparing the effectiveness of ANSWER‐2 with that of educational material on biologic agents will provide further insight into its value in RA management.

     

Risk of Autism Spectrum Disorders in Children Born to Mothers With Rheumatoid Arthritis: A Systematic Literature Review

Objective

There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASD s). We aimed to systematically review the risk of ASD s in children born to mothers with rheumatoid arthritis (RA ) compared to children born to mothers without RA .

Methods

We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science.

Results

Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RA in mothers of children with ASD s versus control mothers. Another case–control study showed a statistically significant 8‐fold increase in autoimmune disorders, including RA , in mothers of offspring with ASD s compared to controls. Forty‐six percent of offspring with ASD s had a first‐degree relative with RA , compared to 26% of controls. And in a population‐based cohort study, investigators observed an increased risk of ASD s in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case–control study design.

Conclusion

Observational studies suggest a potentially increased risk of ASD s in children born to mothers with RA compared to children born to mothers without RA , although data are limited.

     

Course of Grip Force Impairment in Patients With Early Rheumatoid Arthritis Over the First Five Years After Diagnosis

Objective

Objective measures of function are important in rheumatoid arthritis (RA). The objective of this study was to investigate grip strength in patients with early RA.

Methods

An inception cohort of 225 patients with early RA was followed in accordance with a structured protocol. Average and peak grip force values of the dominant hand (measured using a Grippit device [AB Detektor]) were evaluated and compared to expected age‐ and sex‐specific reference values from the literature. Separate analyses were performed for those with limited self‐reported disability (Health Assessment Questionnaire disability index [HAQ DI] score ≤0.5) and clinical remission (Disease Activity Score in 28 joints <2.6).

Results

Baseline average grip force among RA patients was significantly lower than the corresponding expected value (mean 105N versus 266N; P < 0.001). Observed average and peak grip force values were significantly reduced compared to those expected in women as well as in men over time and at all time points. The average grip force improved significantly from inclusion to the 12‐month visit (age‐corrected mean change 34N [95% confidence interval 26–43]). At 5 years, the average grip force was still lower than that expected overall (mean 139N versus 244N; P < 0.001), and also among those with HAQ DI scores ≤0.5 and those in clinical remission.

Conclusion

Grip strength improved in early RA patients, particularly during the first year. However, it was still significantly impaired 5 years after diagnosis, even among those with limited self‐reported disability and those in clinical remission. This suggests that further efforts to improve hand function are important in early RA.

     

Effectiveness of a Web‐Based Personalized Rheumatoid Arthritis Risk Tool With or Without a Health Educator for Knowledge of Rheumatoid Arthritis Risk Factors

Objective

To assess knowledge of rheumatoid arthritis (RA) risk factors among unaffected first‐degree relatives (FDRs) and to study whether a personalized RA education tool increases risk factor knowledge.

Methods

We performed a randomized controlled trial assessing RA educational interventions among 238 FDRs. The web‐based Personalized Risk Estimator for RA (PRE‐RA) tool displayed personalized RA risk results (genetics, autoantibodies, demographics, and behaviors) and educated about risk factors. Subjects were randomly assigned to a Comparison arm (standard RA education; n = 80), a PRE‐RA arm (PRE‐RA alone; n = 78), or a PRE‐RA Plus arm (PRE‐RA and a one‐on‐one session with a trained health educator; n = 80). The RA Knowledge Score (RAKS), the number of 8 established RA risk factors identified as related to RA, was calculated at baseline and post‐education (immediate/6 weeks/6 months/12 months). We compared RAKS and its components at each post‐education point by randomization arm.

Results

At baseline before education, few FDRs identified behavioral RA risk factors (15.6% for dental health, 31.9% for smoking, 47.5% for overweight/obesity, and 54.2% for diet). After education, RAKS increased in all arms, higher in PRE‐RA and PRE‐RA Plus than Comparison at all post‐education points (P < 0.05). PRE‐RA subjects were more likely to identify risk factors than those who received standard education (proportion agreeing that smoking is a risk factor at 6 weeks: 83.1% in the PRE‐RA Plus arm, 71.8% in the PRE‐RA arm, and 43.1% in the Comparison arm; P < 0.05 for PRE‐RA versus Comparison).

Conclusion

Despite being both familiar with RA and at increased risk, FDRs had low knowledge about RA risk factors. A web‐based personalized RA education tool successfully increased RA risk factor knowledge.

     

Fibromyalgia and the Prediction of Two‐Year Changes in Functional Status in Rheumatoid Arthritis Patients

Objective

Previous cross‐sectional studies have shown that rheumatoid arthritis (RA ) patients with fibromyalgia (FM ) have higher disease activity, greater medical costs, and worse quality of life compared to RA patients without FM . We determined the impact of FM on 2‐year changes in the functional status of RA patients in a prospective study.

Methods

Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA . Subjects completed questionnaires, including the Multi‐Dimensional Health Assessment Questionnaire (MDHAQ ) and Polysymptomatic Distress (PSD ) scale, semiannually, and underwent physical examination and laboratory tests yearly.

Results

Of the 156 included RA subjects, 16.7% had FM , while 83.3% did not. In a multivariable linear regression model adjusted for age, sex, race, baseline MDHAQ score, disease duration, rheumatoid factor/cyclic citrullinated peptide antibody seropositivity, disease activity, and psychological distress, RA patients with FM had a 0.14 greater 2‐year increase in MDHAQ score than RA patients without FM (P = 0.021). In secondary analyses examining the association between continuous PSD scale score and change in MDHAQ , higher PSD scale scores were significantly associated with greater 2‐year increases in MDHAQ score (β coefficient 0.013, P = 0.011).

Conclusion

Both the presence of FM and increasing number of FM symptoms predicted worsening of functional status among individuals with RA . Among individuals with RA and FM , the magnitude of the difference in changes in MDHAQ was 4‐ to 7‐fold higher than typical changes in MDHAQ score among individuals with established RA .

     

Foot Barriers in Patients With Early Rheumatoid Arthritis: An Interview Study Among Swedish Women and Men

Objective

Foot impairments are related to reduced mobility and participation restrictions in daily activities in patients with established rheumatoid arthritis (RA). The new biologic medications are effective and reduce disease activity, but not disability to the same extent. Foot impairments are assumed to be related to participation restrictions also in patients with early RA, diagnosed after the introduction of biologic medications. Knowledge of foot impairments needs to be explored further after the introduction of biologic disease‐modifying antirheumatic drugs (bDMARDs). The aim of this study was to explore the patients’ perspective of foot impairments related to early RA.

Methods

The sample included 59 patients (ages 20–63 years) who were interviewed about participation dilemmas in daily life using the critical incident technique. The interviews were audio‐recorded and transcribed. Data related to foot impairments were extracted and analyzed thematically. A research partner validated the analysis.

Results

Patients with early RA described a variety of participation restrictions related to foot impairments: foot hindrances in domestic life, foot impairments influencing work, leisure activities restricted by one's feet, struggling to be mobile, and foot impairments as an early sign of rheumatic disease.

Conclusion

There is a need to focus on foot impairments related to early RA, and for health care professionals to understand these signs. A suggestion for future research is to conduct a longitudinal followup of foot impairment related to medication, disease activity, and disability in patients diagnosed after the introduction of bDMARDs.

     

Pain Catastrophizing,Subjective Outcomes,and Inflammatory Assessments Including Ultrasound: Results From a Longitudinal Study of Rheumatoid Arthritis Patients

Objective

Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with important pain‐related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient‐reported outcomes (PROs), composite scores, and assessments of inflammatory activity.

Methods

RA patients starting biologic disease‐modifying antirheumatic drugs were examined at baseline and after 1, 2, 3, 6, and 12 months with PROs (joint pain/patient's global visual analog scale [VAS], modified Health Assessment Questionnaire, Rheumatoid Arthritis Impact of Disease score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, erythrocyte sedimentation rate/C‐reactive protein [CRP] level), ultrasound (US) (gray scale [GS]/power Doppler [PD] of 36 joints and 4 tendons), and pain catastrophizing. The composite scores for Disease Activity Score in 28 joints, Clinical Disease Activity Index, and Simplified Disease Activity Index were calculated. Statistical calculations included independent samples t‐test, paired samples t‐test, one‐way analysis of variance, Pearson's correlations, and linear and logistic regression.

Results

Of 209 patients included, 152 (72.7%) completed 12‐month followup. Pain catastrophizing, PROs, and clinical and inflammatory assessments decreased significantly (P < 0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (P < 0.001) but not with the inflammatory parameters (swollen joint count, CRP level, and GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (P < 0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (P < 0.05).

Conclusion

Pain catastrophizing was strongly associated with PROs and composite measures, but not with markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat‐to‐target strategy.

     

Relationship Between Knee Pain and Infrapatellar Fat Pad Morphology: A Within‐ and Between‐Person Analysis From the Osteoarthritis Initiative

Objective

Inflammation is known to be strongly associated with knee pain in osteoarthritis. The infrapatellar fat pad represents a potential source of proinflammatory cytokines. Yet the relationship between infrapatellar fat pad morphology and osteoarthritis symptoms is unclear.

Methods

Here we investigate quantitative imaging parameters of infrapatellar fat pad morphology between painful versus contralateral pain‐free legs of subjects with unilateral knee pain and patients with chronic knee pain versus those of matched pain‐free control subjects. A total of 46 subjects with strictly unilateral frequent knee pain and bilateral radiographic osteoarthritis (Kellgren/Lawrence grade 2/3) were drawn from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain over 4 years and 43 matched pain‐free controls without pain over this period were studied. Infrapatellar fat pad morphology (volume, surface area, and depth) was determined by manual segmentation of sagittal magnetic resonance images.

Results

No significant differences in infrapatellar fat pad morphology were observed between painful versus painless knees of persons with strictly unilateral knee pain (mean difference ?0.7% (95% confidence interval [95% CI] ?0.6, 0.9; P = 0.64) or between chronically painful knees versus matched painless controls (?2.1% [95% CI ?2.2, 1.1]; P = 0.51).

Conclusion

Independent of the ambiguous role of the infrapatellar fat pad in knee osteoarthritis (a potential source of proinflammatory cytokines or a mechanical shock absorber), the size of the infrapatellar fat pad does not appear to be related to knee pain.

     

Albuminuria in Rheumatoid Arthritis: Associations With Rheumatoid Arthritis Characteristics and Subclinical Atherosclerosis

Objective

Albuminuria is a marker for subclinical cardiovascular disease (CVD ) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA ), a population with increased atherosclerosis and CVD events.

Methods

Urine albumin from a spot morning collection was measured, and the urine albumin‐to‐creatinine ratio (uACR ) was calculated for RA patients and a population‐based sample of demographically matched non‐RA controls. Associations of elevated uACR (≥25 mg/gm for women and ≥17 mg/gm for men) with CVD risk factors and measures of atherosclerosis (coronary artery calcification, ultrasound‐determined maximal intima‐media thickness of the common carotid artery and internal carotid artery [ICA ], and the presence of focal plaque in the ICA ) were compared cross‐sectionally according to RA status.

Results

We compared 196 RA patients with 271 non‐RA controls. Elevated uACR was found in 18% of the RA patients compared with 17% of the controls (P = 0.89). After adjustment, RA was associated with 57% lower odds of elevated uACR (P = 0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group but not in the RA group (both P for interaction < 0.05). Among RA characteristics, the adjusted prevalence of elevated uACR among those treated with tumor necrosis factor inhibitors was less than half that among those not so treated (9% versus 20%, respectively; P = 0.047).

Conclusion

There was no association in the RA group of elevated uACR with measures of atherosclerosis or with several key cardiometabolic risk factors, which suggests a lower usefulness of elevated uACR as an indicator of subclinical CVD in RA.