Comparable Rates of Glucocorticoid‐Associated Adverse Events in Patients With Polymyalgia Rheumatica and Comorbidities in the General Population

Objective

To investigate the use of glucocorticoids (GCs) and related adverse events (AEs) in a long‐term, geographically defined cohort of patients with polymyalgia rheumatica (PMR).

Methods

Using a population‐based inception cohort, details of GC therapy were abstracted from medical records of all patients diagnosed with PMR in 2000–2014. Age‐ and sex‐matched comparators without PMR were identified from the same underlying population. Cumulative and daily dosage of GC, rate of disease relapse, occurrence of GC‐related AEs, and rate of GC discontinuation were analyzed.

Results

The study included 359 patients with PMR and 359 comparators. The median time to taper below 5 mg/day for 6 months was 1.44 years (95% confidence interval [95% CI] 1.36–1.62), while the median time to permanent discontinuation was 5.95 years (95% CI 3.37–8.88). The mean ± SD cumulative dose of GC at 2 and 5 years was 4.0 ± 3.5 grams and 6.3 ± 9.8 grams, respectively. The mean ± SD daily dose of GC at 2 and 5 years was 6.1 ± 7.6 mg/day and 7.2 ± 9.5 mg/day, respectively. There were no differences in rates of AEs between patients with PMR and comparators for diabetes mellitus, hypertension, hyperlipidemia, or hip, vertebral, or Colles fractures (P > 0.2 for all). Cataracts were more common in patients with PMR than comparators (hazard ratio 1.72 [95% CI 1.23–2.41]).

Conclusion

Relapse rates in PMR are highest in the early stages of therapy. Despite often protracted therapy, with the exception of cataracts, the rates of studied morbidities linked to GC are not more common in PMR than comparators.

     

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.

     

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions

Objective

To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies.

Methods

Virtual and face‐to‐face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions.

Results

Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response.

Conclusion

Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.

     

Autoantibodies Targeting Ficolin‐2 in Systemic Lupus Erythematosus Patients With Active Nephritis

Objective

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by the production of various autoantibodies. The aim of this study was to investigate the presence of anti–ficolin‐2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity.

Methods

This is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into 2 groups (low disease activity [SLE Disease Activity Index (SLEDAI) score ≤4, n = 88] and high disease activity [SLEDAI score >4, n = 77]). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti–ficolin‐2 antibodies was performed by enzyme‐linked immunosorbent assay.

Results

Levels of anti–ficolin‐2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with SLEDAI score. They were found to be positive in 61 of 165 SLE patients (37%). The presence of anti–ficolin‐2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti–ficolin‐2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti–ficolin‐2 antibodies than those with nonproliferative LN. The combination of anti–ficolin‐2, anti–ficolin‐3, and anti‐C1q demonstrated a very high specificity (98%) for the diagnosis of active LN.

Conclusion

Our results support the usefulness of anti–ficolin‐2 as a complementary serologic biomarker for the diagnosis of active lupus with renal manifestations.

     

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 .

     

Development and Testing of a Hybrid Measure of Muscle Strength in Juvenile Dermatomyositis for Use in Routine Care

Objective

To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing in 8 muscles (MMT‐8) and the Childhood Myositis Assessment Scale (CMAS) but is more comprehensive than the former and more feasible than the latter.

Methods

The hybrid MMT‐8/CMAS (hMC) is composed of all 8 items of the MMT‐8 and 3 items of the CMAS: time of head lift, assessment of abdominal muscles, and floor rise. The score ranges 0–100, with 100 indicating normal muscle strength. Validation procedures were conducted using 3 large multinational patient samples, including a total of 810 JDM patients.

Results

The hMC revealed face and content validity, good construct validity, excellent test–retest reliability (intraclass correlation coefficient = 0.99), and internal consistency (Cronbach's α = 0.94), strong responsiveness to clinical change over time (standardized response mean = 0.8 among patients judged as improved by the caring physician), and satisfactory capacity to discriminate patients judged as being in the states of inactive disease or low, moderate, or high disease activity by the physician (P < 0.001) or patients whose parents were satisfied or not satisfied with the illness course (P < 0.001).

Conclusion

The hMC was found to possess good measurement properties in a large population of patients with a wide range of disease activity and severity. The new tool, which is primarily intended for use in routine clinical care, should be further tested in other populations of patients evaluated prospectively.

     

Benefits and Sustainability of a Learning Collaborative for Implementation of Treat‐to‐Target in Rheumatoid Arthritis: Results of a Cluster‐Randomized Controlled Phase II Clinical Trial

Objective

We conducted a 2‐phase randomized controlled trial of a learning collaborative to facilitate implementation of treat‐to‐target (T2T) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of T2T in phase I. Here, we report on a second 9 months (phase II), where we examined the maintenance of response in phase I and predictors of greater improvement in T2T adherence.

Methods

We recruited patients from 11 rheumatology sites and randomized them to either receive the learning collaborative during phase I or to a wait‐list control group that received the learning collaborative intervention during phase II. The outcome was change in T2T implementation score (0–100, where 100 = best) from pre‐ to postintervention. The T2T implementation score was defined as a percent of components documented in visit notes. Analyses examined the extent to which the phase‐I intervention teams sustained improvement in T2T, as well as predictors of T2T improvement.

Results

The analysis included 636 RA patients. At baseline, the mean T2T implementation score was 11% in phase I intervention sites and 13% in phase II sites. After the intervention, T2T implementation score improved to 57% in the phase I intervention sites and to 58% in the phase II sites. Intervention sites from phase I sustained the improvement during the phase II (52%). Predictors of greater T2T improvement included having only rheumatologist providers at the site, academic affiliation of the site, having fewer providers per site, and the rheumatologist provider being a trainee.

Conclusion

Improvement in T2T remained relatively stable over a postintervention period.

     

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.

     

Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration

Objective

To define candidate criteria within multiphase development of systemic lupus erythematosus (SLE) classification criteria, jointly supported by the American College of Rheumatology and the European League Against Rheumatism. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a nominal group technique exercise. Our objectives were to apply an evidence‐based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains.

Methods

A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of antinuclear antibody (ANA) as an entry criterion and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process.

Results

Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp‐2 cells immunofluorescence) as an entry criterion and to have 7 clinical and 3 immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified.

Conclusion

Using a data‐driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale.

     

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.

     

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.

     

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.

     

Improving Adherence to Exercise: Do People With Knee Osteoarthritis and Physical Therapists Agree on the Behavioral Approaches Likely to Succeed?

Objective

To describe which behavior change techniques (BCTs) to promote adherence to exercise have been experienced by people with knee osteoarthritis (OA) or used by physical therapists, and to describe patient‐ and physical therapist–perceived effectiveness of a range of BCTs derived from behavioral theory.

Methods

Two versions of a custom‐designed survey were administered in Australia and New Zealand, one completed by adults with symptomatic knee OA and the second by physical therapists who had treated people with knee OA in the past 6 months. Survey questions ascertained the frequency of receiving/prescribing exercise for knee OA, BCTs received/used targeting adherence to exercise, and perceived effectiveness of 36 BCTs to improve adherence to prescribed exercise.

Results

A total of 230 people with knee OA and 143 physical therapists completed the survey. Education about the benefits of exercise was the most commonly received/used technique by both groups. People with knee OA rated the perceived effectiveness of all BCTs significantly lower than the physical therapists (mean difference 1.9 [95% confidence interval 1.8–2.0]). When ranked by group mean agreement score, 2 BCTs were among the top 5 for both groups: development of specific goals related to knee pain and function; and review, supervision, and correction of exercise technique at subsequent treatment sessions.

Conclusion

Goal‐setting techniques related to outcomes were considered to be effective by both respondent groups, and testing of interventions incorporating these strategies should be a research priority.

     

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease

Objective

To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs).

Methods

Serum Th1 and Th2 cytokines, including interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐10 (IL‐10), IL‐6, IL‐4, and IL‐2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre‐IVIG, at 3 days after temperature normalization following IVIG treatment [post‐IVIG], and 1 month posttreatment).

Results

Levels of IL‐6, IL‐10, TNFα, and IFNγ were significantly increased in KD patients pre‐IVIG. Post‐IVIG, the levels of IL‐6, IL‐10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post‐IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post‐IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL‐4, IL‐6, IL‐10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post‐IVIG levels of IL‐6 and IL‐10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre‐IVIG, an IL‐10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post‐IVIG, an IL‐6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL‐10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs.

Conclusion

Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

     

Pelvic and Hip Kinematics During Walking in People With Patellofemoral Joint Osteoarthritis Compared to Healthy Age‐Matched Controls

Objective

Patellofemoral (PF) joint osteoarthritis (OA) is common, yet little is known about how this condition influences lower‐extremity biomechanical function. This study compared pelvis and lower‐extremity kinematics in people with and without PF joint OA.

Methods

Sixty‐nine participants (64% women, mean ± SD age 56 ± 10 years) with anterior knee pain aggravated by PF joint–loaded activities (e.g., stair ambulation, rising from sitting, or squatting) and radiographic lateral PF joint OA on skyline radiographs were compared with 18 controls (78% women, mean ± SD age 53 ± 7 years) with no lower‐extremity pain or radiographic OA. Knee Injury and Osteoarthritis Outcome Score (KOOS) data were collected from participants with PF joint OA. Quantitative gait analyses were conducted during overground walking at a self‐selected speed. Pelvis and lower‐extremity kinematics were calculated across the stance phase. Data were statistically analyzed using analyses of covariance, with age and sex as covariates (P < 0.05).

Results

Participants with PF joint OA reported a mean ± SD KOOS pain subscale score of 65 ± 15, KOOS symptoms subscale score of 63 ± 16, KOOS activities of daily living subscale score of 73 ± 13, KOOS sports/recreation subscale score of 45 ± 23, and KOOS quality of life subscale score of 43 ± 16. Participants with PF joint OA walked with greater anterior pelvic tilt throughout the stance phase, as well as greater lateral pelvic tilt (i.e., pelvis lower on the contralateral side), greater hip adduction, and lower hip extension during the late stance phase. No differences in knee and ankle joint angles were observed between groups.

Conclusion

People with PF joint OA walk with altered pelvic and hip movement patterns compared with aged‐matched controls. Restoring normal movement patterns during walking in people with PF joint OA may be warranted to help alleviate symptoms.

     

Longitudinal Geographic Miss (LGM) in Robotic Assisted Versus Manual Percutaneous Coronary Interventions

Objectives

To evaluate the impact of robotic‐assisted percutaneous coronary intervention (RA‐PCI) versus manual PCI (M‐PCI) on the incidence of Longitudinal Geographic Miss (LGM).

Background

The safety and feasibility of RA‐PCI has been established in preclinical animal trials and human clinical trials. Patients with LGM have been shown to have worse clinical outcomes including significantly increased incidences of MACE.

Methods

Patients with significant coronary artery disease underwent RA‐PCI in the PRECISE study (n=164) and standard M‐PCI in the STLLR trial (n = 1,509). Longitudinal geographic miss was defined as cases where the entire length of the injured or stenotic segment was not fully covered by the total length of the stent. The incidence of LGM was compared between RA‐PCI and M‐PCI cohorts.

Results

The RA‐PCI cohort had a significantly greater prevalence of previous MI, previous coronary revascularization, and unstable angina. The robotic cohort exhibited a lower incidence of LGM when compared to the M‐PCI patients, 12.2% to 43.1%, respectively (P < 0.0001). To account for the differences in baseline characteristics between the two studies, a propensity score analysis was conducted. The propensity modeling showed similar rates of LGM in both a larger group of patients that met key PRECISE study inclusion/exclusion criteria adjusted for propensity score (9.3% vs 55.0%; P < 0.0001) and in a smaller, matched on propensity score, subset of patients (10.3% vs 64.1%; P < 0.0001).

Conclusion

Robotic‐assisted PCI had significantly lower incidence of LGM compared to standard M‐PCI. Reducing LGM potentially improves long‐term clinical outcomes through reduction in MACE. (J Interven Cardiol 2015;28:449–455)

     

Association Between Metabolic Syndrome and Radiographic Hand Osteoarthritis: Data From a Community‐Based Longitudinal Cohort Study

Objective

To explore whether metabolic syndrome and its components are associated with hand osteoarthritis (OA) using longitudinal data from the Framingham Study.

Methods

Our cross‐sectional analyses included 1,089 persons (ages 50–75 years), of whom 785 had longitudinal radiographs obtained 7 years apart. Of these, 586 with no hand OA at baseline were included in analyses of hand OA incidence. We explored associations between metabolic syndrome and its components (central obesity, hypertension, diabetes mellitus, triglyceridemia, and low high‐density lipoprotein) and radiographic hand OA (defined as ≥2 interphalangeal joints with a Kellgren/Lawrence [K/L] grade of ≥2) using logistic regression analyses with adjustment for age, sex, and body mass index. In longitudinal analyses, metabolic syndrome was used as a predictor for change in K/L sum score and incident hand OA.

Results

Metabolic syndrome was not associated with the presence of hand OA (odds ratio [OR] 1.11 [95% confidence interval (95% CI) 0.78–1.59]), change in K/L sum score (OR 0.83 [95% CI 0.59–1.17]), or incidence of hand OA (OR 0.91 [95% CI 0.58–1.44]). Hypertension was borderline significantly associated with the presence of hand OA (OR 1.25 [95% CI 0.90–1.74]), and a significant association was found between hypertension and change in K/L sum score (OR 1.47 [95% CI 1.08–1.99]). Consistent dose‐response relationships were not demonstrated (data not shown). Furthermore, hypertension was not significantly associated with hand OA incidence (OR 1.23 [95% CI 0.82–1.83]). No significant associations were found between metabolic syndrome and erosive hand OA.

Conclusion

We found no association between metabolic syndrome and hand OA. The role of hypertension in hand OA pathogenesis warrants further investigation.

     

Dynamic Effects of Depressive Symptoms on Osteoarthritis Knee Pain

Objective

To estimate the dynamic causal effects of depressive symptoms on osteoarthritis (OA) knee pain.

Methods

Marginal structural models were used to examine dynamic associations between depressive symptoms and pain over 48 months among older adults (n = 2,287) with radiographic knee OA (Kellgren/Lawrence grade 2 or 3) in the Osteoarthritis Initiative. Depressive symptoms at each annual visit were assessed (threshold ≥16) using the Center for Epidemiologic Studies Depression Scale. OA knee pain was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, rescaled to range from 0 to 100.

Results

Depressive symptoms at each visit were generally not associated with greater OA knee pain at subsequent time points. Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients ranged from 1.78 (95% confidence interval [95% CI] ?0.73, 4.30) to 2.58 (95% CI 0.23, 4.93) within the first and fourth years, and the depressive symptoms by time interaction were not statistically significant (P = 0.94). However, there was a statistically significant dose‐response relationship between the persistence of depressive symptoms and OA knee pain severity (P = 0.002). Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients were 0.89 (95% CI ?0.17, 1.96) for 1 visit with depressive symptoms, 2.35 (95% CI 0.64, 4.06) for 2 visits with depressive symptoms, and 3.57 (95% CI 0.43, 6.71) for 3 visits with depressive symptoms.

Conclusion

The causal effect of depressive symptoms on OA knee pain does not change over time, but pain severity significantly increases with the persistence of depressed mood.

     

Nationwide Experience With Off‐Label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Objective

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Methods

In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti–IL‐1 treatment for at least 6 months were reviewed.

Results

In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18–68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1–48), and the mean colchicine dose was 1.7 mg/day (range 0.5–4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti–IL‐1 treatment was used because of colchicine‐resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6–98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine‐resistant FMF patients were attack free. Serum levels of C‐reactive protein, erythrocyte sedimentation rate, and 24‐hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced.

Conclusion

Anti–IL‐1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine‐resistant FMF patients.

     

Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty

Objective

The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.

Methods

A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity‐adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI ) within 1 year.

Results

Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8–12 weeks was not associated with an increase in infection within 30 days (propensity‐adjusted odds ratio [OR ] 0.90 [95% confidence interval (95% CI ) 0.60–1.34]). The rate of PJI was 2.9 per 100 person‐years and was not increased in patients with stop timing <4 weeks versus 8–12 weeks (hazard ratio [HR ] 0.98 [95% CI 0.52–1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30‐day infection (OR 2.11 [95% CI 1.30–3.40]) and PJI (HR 2.70 [95% CI 1.30–5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.

Conclusion

Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short‐ or long‐term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk.