ObjectiveTo conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens.Data SourcesWe searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles.Study Eligibility Criteria, Participants, and InterventionsWe included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence.Study Appraisal and Synthesis MethodsData abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis.ResultsThe estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures.LimitationsThe meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used.ConclusionsThis analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it.

Depression and Medication Adherence in the Treatment of Chronic Diseases in the United States

With the continued spread of COVID‐19 globally, it is crucial to identify the potential risk or protective factors associated with COVID‐19. Here, we performed genetic correlation analysis and Mendelian randomization analysis to examine genetic relationships between COVID‐19 hospitalization and 405 health conditions and lifestyle factors in 456 422 participants from the UK Biobank. The genetic correlation analysis revealed 134 positive and 65 negative correlations, including those with intakes of a variety of dietary components. The MR analysis indicates that a set of body fat‐related traits, maternal smoking around birth, basal metabolic rate, lymphocyte count, peripheral enthesopathies and allied syndromes, blood clots in the leg, and arthropathy are causal risk factors for severe COVID‐19, while higher education attainment, physical activity, asthma, and never smoking status protect against the illness. Our findings have implications for risk stratification in patients with COVID‐19 and the prevention of its severe outcomes.

A phenome‐wide investigation of risk factors for severe COVID‐19

Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the “treat-to-target” approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs. 

/pdf/the-second-decade-of-anti-tnf-a-therapy-in-clinical-practice-2psi11ke.pdf

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

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Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

A growing number of health insurance data analyses show an increase in the prevalence of rheumatoid arthritis (RA) in Germany. The studies refer to the claims diagnosis of RA, which is more frequent in recent years compared to earlier periods. Depending on the case definition, the numbers vary between 0.6% and 1.4% of the adult population. In this paper, the different studies are reviewed with regard to their data sources, the case definitions of RA and the frequency of the diagnosis. Due to the lack of clinical validation, the prevalence cannot be precisely determined from claims data.Immer mehr Auswertungen von Krankenkassendaten zeigen einen Anstieg der Prävalenz der rheumatoiden Arthritis (RA) in Deutschland. Die Studien beziehen sich auf die Abrechnungsdiagnose einer RA, die in Krankenkassendaten in den letzten Jahren im Vergleich zu früheren Zeiträumen häufiger zu finden ist. Je nach Falldefinition variieren die Zahlen zwischen 0,6% und 1,4% der erwachsenen Bevölkerung. In dieser Arbeit werden die verschiedenen Studien hinsichtlich der Datenquellen, der Falldefinitionen einer RA und der Diagnosehäufigkeit beleuchtet. Aufgrund der fehlenden klinischen Validierung lässt sich die Prävalenz anhand von Abrechnungsdaten nicht präzise bestimmen. 

/pdf/steigt-die-pravalenz-der-rheumatoiden-arthritis-wirklich-an-1v9mfsqd.pdf

Steigt die Prävalenz der rheumatoiden Arthritis wirklich an?

Objectives To compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population. Methods In this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population. Results After 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years. Conclusions Survival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.

All-cause mortality in systemic rheumatic diseases under treatment compared with the general population, 2015-2019.

Objectives Depression and anxiety are linked bi-directionally with inflammatory rheumatic diseases (IRDs) activity, which in turn, depends on subjective patient reported outcomes that can be distorted by comorbid mood disorders. We tested the hypothesis that introduction and/or switching of biologic agents for IRDs are associated with treatment for depression and/or anxiety, by analysing real-world data. Methods Using a country-wide electronic prescription database (10 012 604 registered, 99% population coverage), we captured almost all patients with rheumatoid arthritis (n=12 002), psoriatic arthritis (n=5465) and ankylosing spondylitis (n=6423) who received biologic disease modifying anti-rheumatic drugs (bDMARDs) during a 2-year period (8/2016–7/2018). Concomitant antidepressant/anxiolytic medication use was documented in patients who started or switched bDMARDs and compared with those who remained on conventional synthetic (cs)DMARDs or the same bDMARD, respectively, by multivariate regression analysis. Results Two-year data analysis on 42 815 patients revealed that bDMARD introduction was associated with both antidepressant [OR: 1.248, 95% CI 1.153 to 1.350, p Conclusion In real-world settings, both introduction and switching of bDMARDs in patients with IRDs were associated with the presence of mood disorders. Although a causal relationship is uncertain, the impact of depression and anxiety should always be considered by physicians facing the decision to introduce or switch bDMARDs in patients with active IRDs.

https://rmdopen.bmj.com/content/rmdopen/6/3/e001303.full.pdf

Introduction and switching of biologic agents are associated with antidepressant and anxiolytic medication use: data on 42 815 real-world patients with inflammatory rheumatic disease

Background: Nationwide data at a country level on Covid-19 in unvaccinated patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are scarce. Methods: By interlinking data from national electronic registries, covering nearly 99% of the Greek population (approximately 11,000,000), between March 2020 and February 2021, when vaccination became available, we recorded confirmed infections and Covid-19-associated hospitalizations and deaths in essentially all adult patients with RA, AS, PsA, SLE, and SSc under treatment (n=74,970, median age of 67.5, 51.2, 58.1, 56.2, 62.2 years, respectively) and in individually matched (1:5) on age, sex, and region of domicile random comparators from the general population. Results: Binary logistic regression analysis after adjusting for age, sex and biologic agents, revealed that RA, PsA, SLE and SSc, but not AS patients, had significantly higher risk of infection (by 43%, 25%, 20% and 49%, respectively), and hospitalization for Covid-19 (by 81%, 56%, 94%, and 111%, respectively), possibly due, at least in part, to increased testing and lower threshold for admission. Patients with RA and SSc had indeed higher Covid-19 associated mortality rates [OR:1.86 (95% CI 1.37 to 2.52) and OR:2.90 (95% CI 0.97 to 8.67), respectively] compared to the general population. Each additional year of age increased the risk of hospitalization for Covid-19 by 3% (OR 1.030, 95% CI: 1.028 to 1.034) and the risk of Covid-19 related death by 8% (OR 1.08, 95% CI: 1.07 to 1.09), independently of gender, systemic rheumatic disease, and biologic agents. A further analysis using AS patients as the reference category, adjusting again for age, sex and use of biologic agents showed that patients with SSc had increased mortality (OR: 6.90, 95% CI: 1.41 to 33.72), followed by SLE (OR: 4.05 95% CI: 0.96 to 17.12) and RA patients (OR: 3.65, 95% CI: 1.06 to 12.54), whereas PsA patients had comparable mortality risk with AS patients. Conclusion: Comparing to the general population, Covid-19 may have a more severe impact in real-world patients with systemic rheumatic disease. Covid-19 related mortality is increased in subgroups of patients with specific rheumatic diseases, especially in older ones, underscoring the need for priority vaccination policies and access to targeted treatments.

https://doi.org/10.1101/2022.03.11.22271887

Different COVID-19 outcomes among systemic rheumatic diseases: a nation-wide cohort study

OBJECTIVES
Patients with rheumatoid arthritis (RA) were at increased risk for COVID-19-associated hospitalization and death during the first year of pandemic in Greece. We aimed to examine their outcomes after SARS-Cov-2 Omicron, a more contagious but with milder clinical impacts variant prevailed.


METHODS
A retrospective, nationwide study was conducted between 1-January-2022 and 30-June-2022 in all RA patients under treatment and matched (1:5) on age, sex, and region of domicile random general population comparators. Confirmed SARS-CoV-2 infections, hospitalizations and deaths, anti-rheumatic medications, prior COVID-19, vaccinations and anti-viral medications were recorded.


RESULTS
Among 34 182 RA patients, infections (n = 5,569, 16.29%), hospitalizations (n = 489, 1.43%) and deaths (n = 106, 0.31%) were more frequent than comparators. Incidence rates per 1000 person/years of infection [IRR (95%CI):1.19 (1.16-1.23)], hospitalization [IRR (95%CI):2.0 (1.82-2.24)], and death [IRR (95%CI):1.81 (1.44-2.27)] were increased in RA despite better vaccination coverage (89% vs 84%) and more frequent use of anti-viral medications (2.37% vs 1.08). Logistic regression analysis after correcting for age, sex, vaccinations, prior COVID-19, anti-viral and anti-rheumatic medications in SARS-CoV-2 infected RA patients and comparators revealed increased risk of hospitalization (OR : 2.02, 95%CI : 1.79- 2.27) and death [OR : 1.73, (95%CI : 1.36-2.20)] in RA. Among infected RA patients rituximab treatment conferred increased risks for hospitalization [OR: 6.12, (95%CI : 2.89-12.92)] and death [OR : 12.06 (95%CI : 3.90-37.31)], while JAK inhibitors increased only hospitalization risk [OR : 2.18 (95%CI : 1.56-3.06)].


CONCLUSION
RA remains a risk factor for hospitalization and death in an era of a relatively low COVID-19 fatality rate, pointing to the need of perseverance in vaccination programs and wider use of anti-viral medications.

Konstantinos Mathioudakis

Papers

All-cause mortality in systemic rheumatic diseases under treatment compared with the general population, 2015-2019.

Introduction and switching of biologic agents are associated with antidepressant and anxiolytic medication use: data on 42 815 real-world patients with inflammatory rheumatic disease

Different COVID-19 outcomes among systemic rheumatic diseases: a nation-wide cohort study

Outcomes of COVID-19 Omicron variant in patients with rheumatoid arthritis: a nationwide Greek cohort study.