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.

     

Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis

Objective

To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort.

Methods

We conducted a cross‐sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy–adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C‐reactive protein (CRP) level. We also estimated the difference in DAS28‐CRP associated with increasing fish consumption by 1 serving per week.

Results

Among 176 participants, the median DAS28‐CRP score was 3.5 (interquartile range 2.9–4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28‐CRP compared with subjects who ate fish never to <1 time/month (difference ?0.49 [95% CI ?0.97, ?0.02]). For each additional serving of fish per week, DAS28‐CRP was significantly reduced by 0.18 (95% CI ?0.35, ?0.004).

Conclusion

Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.

     

General and Abdominal Obesity as Risk Factors for Late‐Life Mobility Limitation After Total Knee or Hip Replacement for Osteoarthritis Among Women

Objective

To investigate associations of body mass index (BMI), waist circumference (WC), and waist/hip ratio (WHR) with survival to age 85 years with mobility limitation or death before age 85 years among older women with total knee replacement (TKR) or total hip replacement (THR) for osteoarthritis (OA).

Methods

This was a prospective study of women (ages 65–79 years at baseline) from the Women's Health Initiative, recruited during 1993–1998 and followed through 2012. Women's Health Initiative data were linked to Medicare claims data to determine TKR (n = 1,867) and THR (n = 944) for OA. Women were followed for up to 18 years after undergoing THR or TKR to determine mobility status at age 85 years.

Results

Compared with normal‐weight women, overweight, obese I, and obese II women with THR had significantly increased risk of survival to age 85 years with mobility limitation (P < 0.001 for linear trend), with the strongest risk among obese II women (odds ratio [OR] 4.37 [95% confidence interval (95% CI) 1.96–9.74]). Obese II women with THR also had increased risk of death before age 85 years. Women with THR and WC >88 cm relative to ≤88 cm had increased risk of survival to age 85 years with mobility limitation (OR 1.65 [95% CI 1.17–2.33]) but not death before age 85 years. High BMI, WC, and WHR were associated with significantly increased risk of late‐life mobility limitation and death among women with TKR for OA.

Conclusion

Among older women who underwent THR or TKR for OA, baseline general and abdominal obesity were associated with increased risk of late‐life mobility limitation.

     

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.

     

Skeletal Muscle Fat and Its Association With Physical Function in Rheumatoid Arthritis

Objective

To characterize skeletal muscle fat (SMF), intermuscular adipose tissue (IMAT), and subcutaneous adipose tissue (SAT) in individuals with rheumatoid arthritis (RA), and assess the associations between these fat depots and physical function and physical activity.

Methods

In a cross‐sectional analysis from an RA cohort, SMF, IMAT, and SAT were measured using computed tomography imaging of the midthigh cross‐sectional region. Physical function was measured using the Health Assessment Questionnaire (HAQ) and a battery of performance‐based tests that included quadriceps muscle strength, gait speed, repeated chair‐stands, stair ascent, and single‐leg stance. Physical activity was assessed using an activity monitor. Associations between SMF, IMAT, and SAT and physical function and activity were assessed by multiple linear regression models adjusted for potential confounders such as age, sex, body mass index (BMI), muscle area, and muscle strength.

Results

Sixty subjects with RA (82% female, mean ± SD age 59 ± 10 years, mean ± SD BMI 31.79 ± 7.16 kg/m²) were included. In the adjusted models, lower SMF was associated with greater gait speed, single‐leg stance, quadriceps strength, and physical activity, and less disability (R²Δ range 0.06–0.25; P < 0.05), whereas IMAT was not associated with physical function or physical activity and SAT was negatively associated with disability (HAQ) (R²Δ = 0.13; P < 0.05) and weakly but positively associated with muscle strength (R²Δ = 0.023; P < 0.05).

Conclusion

Fat infiltration within the muscle seems to independently contribute to low physical function and physical activity, contrary to IMAT or SAT accumulation. Longitudinal studies are necessary to confirm the impact of SMF on disability and health promotion in persons with RA.

     

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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

Trends in Hospitalizations for Serious Infections in Patients With Rheumatoid Arthritis in the US Between 1993 and 2013

Objective

The epidemiology of hospitalizations with infections among patients with rheumatoid arthritis (RA) is unknown, despite an increase in RA treatments that confer a risk of infection.

Methods

We examined National Inpatient Sample data from 1993–2013. We identified hospitalizations among adults with RA, defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes (714.xx) in any secondary diagnosis field. We evaluated 5 infections as the primary diagnosis: pneumonia, sepsis, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), and opportunistic infections (OIs). The primary outcome was the proportion of hospitalizations for each infection among all hospitalizations with a secondary diagnosis of RA.

Results

There were 792,921 hospitalizations for infection with a secondary diagnosis of RA, with the rates increasing from 90 to 206 per 100,000 persons from 1993–2013. The proportion of hospitalizations decreased for pneumonia (from 5.4% to 4.6%), UTI (from 0.4% to 0.38%), and OIs (from 0.44% to 0.26%). The proportion of hospitalizations for SSTIs increased slightly (from 2.3% to 2.5%), while hospitalizations for sepsis more than tripled (from 1.9% to 6.4%).

Conclusion

Between 1993 and 2013, the proportion of hospitalizations for infections among RA patients appeared to decline for pneumonia and OIs, with a slight decrease in UTI, a slight increase in SSTIs, and a substantial increase in hospitalizations with sepsis. Our results are consistent with previous reports that the sensitivity of sepsis coding has increased over time.

     

Association Between Anti–Citrullinated Fibrinogen Antibodies and Coronary Artery Disease in Rheumatoid Arthritis

Objective

Antibodies against citrullinated fibrinogen (anti–Cit‐fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular risk in RA. The objective of this study was to examine the association between anti–Cit‐fibrinogens and coronary artery disease (CAD) outcomes.

Methods

We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data containing information on CAD outcomes from medical record review. Using a published bead‐based assay method, we measured 10 types of anti–Cit‐fibrinogens. We applied a score test to determine the association between the anti–Cit‐fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti–Cit‐fibrinogens clustered into groups. Each group was then additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome.

Results

We studied 1,006 RA subjects (mean ± SD age 61.0 ± 13.0 years; 72.2% anti–cyclic citrullinated peptide positive). As a group, anti–Cit‐fibrinogen was associated with CAD (P = 1.1 × 10^?4). From the PCA analysis, we observed 3 main groups, of which only 1 group, containing 7 of the 10 anti–Cit‐fibrinogens, was significantly associated with CAD outcomes (P = 0.015). In the sensitivity analysis, all anti–Cit‐fibrinogens as a group remained significantly associated with IHD (P = 2.9 × 10^?4).

Conclusion

Anti–Cit‐fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies.

     

Implementation of Treat‐to‐Target for Rheumatoid Arthritis in the US: Analysis of Baseline Data From a Randomized Controlled Trial

Objective

A treat‐to‐target (TTT) strategy is recommended in rheumatoid arthritis (RA). However, health care providers’ adherence to TTT in clinical practice remains unclear. We examined adherence to TTT in RA at US rheumatology sites.

Methods

We used baseline information from the randomized controlled Treat‐to‐Target in RA: Collaboration to Improve Adoption and Adherence trial, which recruited 641 patients from 46 providers practicing at 11 US sites. We obtained data on the implementation of TTT, patient covariates, provider characteristics, and site variables. We examined the implementation of TTT using 4 cardinal features: recording a disease target, recording a disease activity measure, engaging in shared decision‐making, and changing treatment if not at disease target. These features were assessed across sites and providers. We calculated a TTT implementation score as the percentage of features noted. We examined the association between patient, provider, and site covariates and TTT implementation score using proportional odds models.

Results

The implementation of TTT at baseline was suboptimal: 64.3% of visits had none of the TTT components present, 33.1% had 1 component, 2.3% had 2 components, and 0.3% had all components. The implementation of TTT was significantly different across providers and sites (P < 0.0001 for all). In the multivariable model, we observed that more experience as a rheumatologist was associated with a higher implementation score (P = 0.01 for trend). Compared with fellows, providers with >20 years of experience in practice were more likely to have more TTT components recorded (odds ratio 7.68 [95% confidence interval 1.46–40.52]).

Conclusion

We found that adherence to a TTT strategy in RA was suboptimal, and it differed across providers and sites.

     

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta‐Analysis of Direct and Indirect Trial Evidence

Objective

We undertook a systematic review and meta‐analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA).

Methods

We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA).

Results

Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta‐analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies.

Conclusion

Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.

     

Timing and Impact of Decisions to Adjust Disease‐Modifying Antirheumatic Drug Therapy for Rheumatoid Arthritis Patients With Active Disease

Objective

Guidelines recommend that rheumatoid arthritis (RA) patients with moderate‐to‐high disease activity (MHDAS) adjust disease‐modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner.

Methods

We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS.

Results

We identified 538 eligible subjects with 943.5 patient‐years of followup. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 (interquartile range [IQR] 1–706) days and 301 (IQR 140–706) days, respectively. Being elderly (subdistribution hazard ratio [SHR] 0.61, P = 0.02), lower baseline disease activity (SHR 0.72, P < 0.01), longer duration of RA (SHR 0.98, P < 0.01), and biologic use (SHR 0.71, P < 0.01) were significantly associated with longer times to therapy adjustment. African American race (hazard ratio [HR] 0.63, P = 0.01), higher baseline disease activity (HR 0.75, P < 0.01), and not adjusting DMARD therapy within 90 days (HR 0.76, P = 0.01) were associated with longer times to LDAS.

Conclusion

Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited >90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS.

     

Projected Burden of Osteoarthritis and Rheumatoid Arthritis in Australia: A Population‐Level Analysis

Objective

To forecast the prevalence and direct health care costs of osteoarthritis (OA) and rheumatoid arthritis (RA) in Australia to the year 2030.

Methods

An epidemiologic model of the Australian population was developed. Data on the national prevalence of OA and RA were obtained from the Australian Bureau of Statistics (ABS) 2014–2015 National Health Survey. Future prevalence was estimated using ABS population projections for 2020, 2025, and 2030. Available government data on direct health care expenditure for OA and RA were modeled to forecast costs (in Australian $) for the years 2020, 2025, and 2030, from the perspective of the Australian public health care system.

Results

The number of people with OA is expected to increase nationally from almost 2.2 million in 2015 to almost 3.1 million Australians in 2030. The number of people with RA is projected to increase from 422,309 in 2015 to 579,915 in 2030. Health care costs for OA were estimated to be over $2.1 billion in 2015; by the year 2030, these are forecast to exceed $2.9 billion ($970 for every person with the condition). Health care costs for RA were estimated to be over $550 million in 2015, including $273 million spent on biologic disease‐modifying antirheumatic drugs. Health care costs for RA are projected to rise to over $755 million by the year 2030.

Conclusion

OA and RA are costly conditions that will impose an increasing health care burden at the population level. These projections provide tangible data that can be used to map future health service provision to expected need.