Cognitive Impairment in Rheumatoid Arthritis: A Systematic Review

Objective

Rheumatoid arthritis (RA) is not commonly associated with central nervous system and brain changes. However, a number of studies have reported high rates of cognitive impairment in adults with RA. The objective of this systematic review was to identify and explore the rates and types of cognitive impairment in RA.

Methods

Multiple databases were searched for articles published between 1994 and 2016, to identify studies that have included: adults with RA; standardized neuropsychological tests; and sufficient information to ascertain the relationship between cognitive impairment and demographic, clinical, and psychological factors. Of 1,980 titles, 75 were retained at the abstract level, 36 at the full‐text level, and 15 studies in the final review. These were evaluated using a modified Newcastle‐Ottawa Scale, and the findings were synthesized using a narrative approach.

Results

Ten of 15 studies compared RA to other clinical groups and/or a control group. Based on summed effect size analyses, individuals with RA significantly underperformed on cognitive function tests compared to the control groups, particularly on verbal function, memory, and attention. Less clear differences were found between RA and other clinical groups. Some demographic (age and education), clinical (disease activity), and psychological (depression) factors were associated with cognitive impairment, but inconsistently so across studies. A number of limitations were identified: small and predominantly female samples, limited cognitive domain inclusion, lack of study details, and management of confounding variables.

Conclusion

There is evidence of cognitive impairment in adults with RA. Further studies are needed to confirm prevalence rates and examine potential mechanisms.     

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.

     

Systematic Review and Meta-analysis: Mindfulness-Based Interventions for Rheumatoid Arthritis

Purpose of Review

To determine the efficacy of mindfulness-based interventions (MBIs) on clinical and patient-reported outcomes in rheumatoid arthritis (RA).

Recent Findings

We identified randomized clinical trials from inception through April 2018 from MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, the Cochrane Library, and hand searches. After screening 338 references, we included five trials with one post-hoc analysis that evaluated MBIs and collectively included 399 participants. Outcome instruments were heterogeneous across studies. Three studies evaluated RA clinical outcomes by a rheumatologist; one study found improvements in disease activity. A limited meta-analysis found no statistically significant difference in the levels of DAS28-CRP in the two studies that evaluated this metric (??0.44 (??0.99, 0.12); I² 0%). Four studies evaluated heterogeneous psychological outcomes, and all found improvements including depressive symptoms, psychological distress, and self-efficacy. A meta-analysis of pain Visual Analog Scale (VAS) levels post intervention from three included studies was not significantly different between MBI participants and control group (??0.58 (??1.26, 0.10); I² 0%) although other studies not included in meta-analysis found improvement.

Summary

There are few trials evaluating the effect of MBIs on outcomes in patients with RA. Preliminary findings suggest that MBIs may be a useful strategy to improve psychological distress in those with RA.

     

Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

The objective of the work reported in this paper was to critically assess how sequential disease-modifying anti-rheumatic drugs (DMARDs) have been modelled in the context of economic evaluation of the use of DMARDs for treatment of rheumatoid arthritis (RA). A secondary purpose was to identify the methodological challenges of modelling sequential therapies. Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were in the English language and a full comparative economic evaluation was reported. They were appraised by use of the Drummond checklist (Appendix to this paper). Data extracted included economic evaluation data, data relating to sequential treatment, and data on the modelling methods used. Fifty-seven studies were identified, with 25 (44 %) modelling a sequence of treatments. Forty-three (75 %) were cost–utility analyses. Eleven (19 %) were UK studies and 11 (19 %) were US. The remainder were mainly European (26 (46 %)). A distinction was made between studies of recent-onset RA (14 (25 %)) and those of established RA (42 (74 %)). One study (1 %) was unclear. Individual-level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimum sequence of multiple treatments given a set of treatment options. The level of reporting of the methods and evidence used to assess the effect of downstream treatments in the sequence was generally poor. When lifelong models and downstream treatment sequences were considered, evidence gaps were identified. The review discovered that methods have not been consistently applied, leading to varied estimates of cost-effectiveness. Treatment sequences have not been fully considered and modelled, potentially resulting in inaccurate estimates of cost-effectiveness.     

Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review

Objective

Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis.

Methods

A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov.

Results

Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non‐controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001).

Conclusion

The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo‐controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.

     

Diastolic Dysfunction in Rheumatoid Arthritis: A Meta‐Analysis and Systematic Review

Objective

To determine if the prevalence of diastolic dysfunction is increased in rheumatoid arthritis (RA) patients.

Methods

We conducted a time‐ and language‐restricted literature search to identify studies conducted to compare echocardiographic parameters in patients with RA and controls. The mean difference for echocardiographic variables of interest was calculated using a random‐effects model. A systematic review of the literature was performed.

Results

A total of 25 studies reporting on 5,836 subjects (1,614 with RA) were included. Results reflect mean differences, with positive values denoting higher values in RA patients. Patients with RA had larger mean left atrial dimension (mean difference 0.09 cm [95% confidence interval (95% CI) 0.01, 0.17]; P = 0.02), higher left ventricular mass index (mean difference 6.2 gm/m² [95% CI 1.08, 11.33]; P = 0.02), higher mean systolic pulmonary artery pressure (mean difference 5.87 mm Hg [95% CI 4.36, 7.38]; P < 0.00001), prolonged isovolumetric relaxation time (mean difference 9.67 msec [95% CI 5.78, 13.56]; P < 0.00001), and higher transmitral A wave velocity (mean difference 0.13 meters/second [95% CI 0.07, 0.18]; P < 0.00001) compared to controls. A subanalysis of 2,183 subjects excluding 2 large unmatched studies showed the same results, with the exception that patients with RA had a lower mitral E/A ratio (mean difference ?0.17 [95% CI ?0.25, ?0.09]; P < 0.00001), suggestive of diastolic dysfunction. There were no differences in left ventricular ejection fraction (%), transmitral E wave velocity (meters/second), and mitral deceleration time (msec).

Conclusion

Patients with RA were more likely to have echocardiographic parameters of diastolic dysfunction, and have higher systolic pulmonary artery pressures and larger left atrial sizes.

     

Lipid Paradox in Rheumatoid Arthritis: Changes With Rheumatoid Arthritis Therapies

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality, related not only to traditional CV risk factors, but also to a chronic inflammatory state. However, lipid profiles in RA are different from those observed in the general population at risk of CV disease, where there is evidence of a positive relationship between disease and high cholesterol levels. In untreated patients with active RA this relationship is different, with a paradoxical effect resulting in lower levels of cholesterol associated with an increased risk of CV disease. In this review, we summarize the latest evidence on lipid abnormalities in the setting of RA and the interaction between inflammation and lipoproteins, as well as the effect of DMARDs and biologic therapies on lipid profiles and the possible implications for CV outcomes in this population.