Cachexia measured by bioelectrical impedance vector analysis and risk of infection in women with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients have a higher frequency of infections than the healthy population. The reason has yet to be explained but involves several factors, of which body composition and rheumatoid cachexia are often overlooked. This study aimed to evaluate whether patients with cachexia, measured by bioelectrical impedance vector analysis, are at an increased risk of developing infections compared with patients without cachexia. A secondary analysis of 186 women with RA enrolled in a randomized trial (ClinicalTrials.gov ID: NCT02900898, September 14, 2016) was completed. Medical records and phone calls were used to record infectious events diagnosed and treated during follow-up. Hazard ratios were calculated using Cox proportional hazard regression analysis, and a predictive model of infection was created. After 36 months of follow-up, 62 patients (26.7% non-cachectic and 44.3% cachectic, p < 0.01) developed at least one infectious event. The most common site of was the urinary tract, followed by the lungs and respiratory tract. The presence of cachexia (HR 1.90, 95% CI 1.15-3.13) and the use of glucocorticoids (HR 1.77, 95% CI 1.01-3.09) were associated with infection in univariate and multivariate models. Body mass index (BMI), smoking, and methotrexate use were not associated with a higher frequency of infections. The presence of cachexia and the use of glucocorticoids were identified as predictors of infections in a cohort of female RA patients. More extensive measurements of body composition should be performed beyond BMI in RA patients to better understand its impact and to prevent additional comorbidities and complications. Key Points • The presence of cachexia measured by bioelectrical impedance vector analysis was associated with infectious events in women with rheumatoid arthritis, whereas body mass index did not show an association. • Glucocorticoids were the only drug associated with a higher frequency of infection. None of the disease-modifying antirheumatic drugs, including methotrexate, showed an association.

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. METHODS: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. RESULTS: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI - 5.58, 5.82), BMI 0.08 kg/m2 (95% CI - 1.76, 1.92), FM - 0.08 kg (95% IC - 5.31, 5.14), and FFM - 2.08 kg (95% CI - 7.37, 3.21). CONCLUSION: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. TRIAL REGISTRATION: PROSPERO code: CRD42020206949.

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Cachexia in patients with rheumatoid arthritis: a cohort study.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that leads to altered body composition. The loss of lean mass with a preservation or increase in fat mass has been termed rheumatoid cachexia (RC), to contrast with classic cachexia, which is characterized by severe weight loss. There are limited data on the prevalence and progression of cachexia in RA over time, as well as on associated factors. Our aim was to determine the prevalence of cachexia and to determine associations with potential factors. METHODS: This prospective cohort study recruited consecutively patients diagnosed with RA and followed for 1 year. The assessments were performed: clinical features, body composition, and physical function. RC and classic cachexia were assessed by several established diagnostic criteria. The pairwise Student's t test, Chi-square test, and GEE were performed (accepted at p ≤ 0.05). RESULTS: Of 90 patients recruited, 81 completed the study. Most patients were women (88.9%), and the mean age was 56.5 ± 7.3 years. At baseline, the median DAS28-CRP was 3.0 (IQR, 1.0-3.0), 13.3-30.0% of the included patients had RC, while none met criteria for classic cachexia. The prevalence of cachexia did not change after 12 months. Disease activity status and treatment with biologic disease-modifying antirheumatic drugs were significantly associated with changes on body composition and physical function (p < 0.05). CONCLUSIONS: In this cohort, RC was common, while classic cachexia was absent. Disease activity and use of biologic therapies were associated with changes on body composition and physical function, underscoring the importance of aiming for remission when treating RA.

Fatty acids uptake and oxidation are increased in the liver of rats with adjuvant-induced arthritis.

Severe rheumatoid cachexia is associated with pronounced loss of muscle and fat mass in patients with advanced rheumatoid arthritis. This condition is associated with dyslipidemia and predisposition to cardiovascular diseases. Circulating levels of triglycerides (TG) and free fatty acids (FFA) have not yet been consistently defined in severe arthritis. Similarly, the metabolism of these lipids in the arthritic liver has not yet been clarified. Aiming at filling these gaps this study presents a characterization of the circulating lipid profile and of the fatty acids uptake and metabolism in perfused livers of rats with adjuvant-induced arthritis. The levels of TG and total cholesterol were reduced in both serum (10-20%) and liver (20-35%) of arthritic rats. The levels of circulating FFA were 40% higher in arthritic rats, possibly in consequence of cytokine-induced adipose tissue lipolysis. Hepatic uptake and oxidation of palmitic and oleic acids was higher in arthritic livers. The phenomenon results possibly from a more oxidized state of the arthritic liver. Indeed, NADPH/NADP+ and NADH/NAD+ ratios were 30% lower in arthritic livers, which additionally presented higher activities of the citric acid cycle driven by both endogenous and exogenous FFA. The lower levels of circulating and hepatic TG possibly are caused by an increased oxidation associated to a reduced synthesis of fatty acids in arthritic livers. These results reveal that the lipid hepatic metabolism in arthritic rats presents a strong catabolic tendency, a condition that should contribute to the marked cachexia described for arthritic rats and possibly for the severe rheumatoid arthritis.

Prevalence of rheumatoid cachexia in rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: Low muscle mass occurs in patients with rheumatoid arthritis without weight loss; this condition is referred as rheumatoid cachexia. The aim of the current study was to perform a systematic review with meta-analysis to determine the rheumatoid cachexia prevalence. METHODS: A systematic review with meta-analysis of observational studies published in English, between 1994 and 2016, was conducted using MEDLINE (via PubMed) and other relevant sources. Search strategies were based on pre-defined keywords and medical subject headings. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was used to estimate the prevalence, and because studies reported different methods and criteria to estimate body composition and prevalence of rheumatoid cachexia, subgroup analyses were performed. Meta-regression adjusted for the 28-joint disease activity score and disease duration (years) was performed (significance level at P ≤ 0.05). RESULTS: Of 136 full articles (one duplicate publication) screened for inclusion in the study, eight were included. The estimated overall prevalence of rheumatoid cachexia was 19% [95% confidence interval (CI) 07-33%]. This prevalence was 29% (95% CI 15-46%) when body composition was measured by dual-energy X-ray absorptiometry. When the diagnostic criteria were fat-free mass index below the 10th percentile and fat mass index above the 25th percentile, rheumatoid cachexia prevalence was 32% (95% CI 14-52%). The 28-joint disease activity score and disease duration had no influence on the estimated prevalence of rheumatoid cachexia (P > 0.05). Most studies were rated as having moderate methodological quality. CONCLUSIONS: Meta-analysis showed a prevalence of rheumatoid cachexia of 15-32%, according to different criteria, demonstrating that this condition is a frequent comorbidity of rheumatoid arthritis. To better understand its clinical impact, more studies using standardized definitions and prospective evaluations are urgently needed.

Prevalence of rheumatoid cachexia assessed by bioelectrical impedance vector analysis and its relation with physical function.

Rheumatoid arthritis (RA) patients frequently have changes in their body composition, with a decrease in muscle mass and an increase in fat mass, a syndrome that is termed rheumatoid cachexia (RC). The prevalence of this nutritional alteration is not well known; there is as yet no consensus, seeing as it depends on the methods, techniques, and cutoff points that are used for its diagnosis. The main aim of this study was to identify RC through assessment by bioelectrical impedance vector analysis (BIVA) and its association with metabolic causes, physical function, and the main disease status, among others. The prevalence of RC was identified in those subjects who fell outside the right lower quadrant of the reference curve of RXc graph of BIVA. Clinical, anthropometric, biochemical and physical activity, emotional status, and diet markers were also evaluated. Ninety-four patients were included (92.55% women). The prevalence of RC assessed by BIVA was 21.28%. BIVA-cachexia patients had a lesser value of handgrip strength vs. patients without BIVA-cachexia 10.2 kg (7.2-13.4) vs. 14.7 kg (9.6-19), p = 0.0062. Disability and folic acid with methotrexate consumption are related to BIVA-cachexia ((OR 4.69, 95% CI 1.33, 16.54, p = 0.016) and (OR 0.19, 95%CI 0.058, 0.651, p = 0.008), respectively). BIVA could represent a valuable tool to assess presence of RC. It is important that RA patients have physical therapy to improve their nutritional status.