Muscle loss following a single high-dose intramuscular injection of corticosteroids to treat disease flare in patients with rheumatoid arthritis.

OBJECTIVE: Adverse changes in body composition, specifically decreased muscle mass (MM) and increased fat mass, characterize rheumatoid arthritis (RA). These changes, termed rheumatoid cachexia (RC), are important contributors to the disability and elevated co-morbidity risk of RA. Recently, we observed substantial muscle loss (~2 kg) in a patient with RA following a single intramuscular (IM) corticosteroid (CS) injection to treat a disease flare. The aim of the current study is to determine whether this apparent iatrogenic effect of IM CS is typical, i.e., does this routine, recommended treatment contribute to RC? METHODS: Body composition was assessed by dual-energy X-ray absorptiometry (DXA) in eight patients with established RA who received a 120 mg IM methylprednisolone injection to treat a disease flare. DXA scans estimated appendicular lean mass (ALM; a surrogate measure of MM), total lean mass (LM), and total and regional adiposity at baseline (injection day) and 4 weeks and 6-9 months post-injection. Statistical analysis was performed using one-way ANOVA. RESULTS: There was significant loss of ALM (-0.93 kg, p=0.001, 95% CI [-0.49, -1.36]) and a trend toward reduced LM (-1.10 kg, p=0.165, 95% CI [0.58, -2.79]) at 4 weeks relative to baseline. At 6-9 months despite control of inflammation and disease activity, these losses remained. CONCLUSION: Substantial muscle loss occurred in patients with RA following IM CS injection to treat a disease flare. Thus, this recommended treatment appears to exacerbate RC, thereby potentially increasing disability and co-morbidity risk. If this effect is confirmed by larger studies, the role of one-off high-dose CS in the treatment of RA should be reviewed.

The 8-foot up and go test is the best way to assess physical function in the rheumatoid arthritis clinic.

OBJECTIVES: RA is characterized by poor physical function, which compromises patients' quality of life and outcome. Clinical assessment of function is usually performed using self-reported questionnaires, such as the Multi-Dimensional HAQ (MDHAQ) and the Short Form-36 (physical component) (SF36-PC). However, such subjective measures may not accurately reflect real functional status. This study aimed to determine: (i) which clinically practicable objective test best represents overall physical function; and (ii) the extent to which self-reported subjective functional measures reflect objectively assessed function. METHODS: Objective [isometric knee extensor strength, handgrip strength, sit-to-stands in 30 s, 8-foot up and go (8'UG), 50-foot walk (50'W) and estimated aerobic capacity (V̇O2max)] and subjective (MDHAQ and SF36-PC) measures of function were correlated with one another to determine the best overall test of functional status in 82 well-controlled RA patients (DAS28 (s.d.) = 2.8 (1.0)). RESULTS: In rank order of size, averaged correlations (r) to the other outcome measures were as follows: 8'UG: 0.650; 50'W: 0.636; isometric knee extensor strength: 0.502; handgrip strength: 0.449; sit-to-stands in 30 s: 0.432; and estimated V̇O2max: 0.358. The MDHAQ was weakly (0.361) and the SF36-PC moderately correlated (0.415) with objective measures. CONCLUSION: Our results show that the most appropriate measure of objective physical function in RA patients is the 8'UG, followed by the 50'W. We found discordance between objectively and subjectively measured function. In clinical practice, an objective measure that is simple and quick to perform, such as the 8'UG, is advocated for assessing real functional status.

Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients.

OBJECTIVE: RA typically features rheumatoid cachexia [loss of muscle mass (MM) and excessive total fat mass (TFM), especially trunk FM], which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as treat-to-target (T2T), in attenuating inflammation would benefit body composition and physical function. This aim of this cross-sectional study was to assess the impact of T2T on body composition and objectively assessed function in RA patients. METHODS: A total of 82 RA patients exclusively treated by T2T, were compared with 85 matched sedentary healthy controls (HCs). Body composition was estimated by DXA, with appendicular lean mass the surrogate measure of total MM. Physical function was assessed by knee extensor strength, handgrip strength, 30 s sit-to-stands, 8' up and go, and 50' walk (tests which reflect the ability to perform activities of daily living). RESULTS: Although generally well treated (mean DAS28 = 2.8, with 49% in remission), RA patients had ∼10% proportionally less appendicular lean mass and were considerably fatter (by ∼27%), particularly in the trunk (∼32%), than HCs. All measures of function were 24-34% poorer in the RA patients relative to HC. CONCLUSIONS: Despite marked improvements in disease control (most patients achieving or approaching remission), the relative loss of MM and increased adiposity in RA patients compared with matched HCs was similar to that observed pre-T2T. Additionally, performance of objective function tests was unchanged from that reported by our group for pre-T2T RA patients. Thus T2T, even in responsive RA patients, did not attenuate rheumatoid cachexia or improve objectively assessed function.

Can Creatine Supplementation Improve Body Composition and Objective Physical Function in Rheumatoid Arthritis Patients? A Randomized Controlled Trial.

OBJECTIVE: Rheumatoid cachexia (muscle wasting) in rheumatoid arthritis (RA) patients contributes to substantial reductions in strength and impaired physical function. The objective of this randomized controlled trial was to investigate the effectiveness of oral creatine (Cr) supplementation in increasing lean mass and improving strength and physical function in RA patients. METHODS: In a double-blind design, 40 RA patients were randomized to either 12 weeks' supplementation of Cr or placebo. Body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy [BIS]), strength, and objectively assessed physical function were measured at baseline, day 6, week 12, and week 24. Data analysis was performed by analysis of covariance. RESULTS: Cr supplementation increased appendicular lean mass (ALM; a surrogate measure of muscle mass) by mean ± SE 0.52 ± 0.13 kg (P = 0.004 versus placebo), and total LM by 0.60 ± 0.37 kg (P = 0.158). The change in LM concurred with the gain in intracellular water (0.64 ± 0.22 liters; P = 0.035) measured by BIS. Despite increasing ALM, Cr supplementation, relative to placebo, failed to improve isometric knee extensor strength (P = 0.408), handgrip strength (P = 0.833), or objectively assessed physical function (P = 0.335-0.764). CONCLUSION: In patients with RA, Cr supplementation increased muscle mass, but not strength or objective physical function. No treatment-related adverse effects were reported, suggesting that Cr supplementation may offer a safe and acceptable adjunct treatment for attenuating muscle loss; this treatment may be beneficial for patients experiencing severe rheumatoid cachexia.

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture [ISRCTN22464643].

BACKGROUND: Proximal femoral fracture is a common, major health problem in old age resulting in loss of functional independence and a high-cost burden on society, with estimated health and social care costs of £2.3 billion per year in the UK. Rehabilitation has the potential to maximise functional recovery and maintain independent living, but evidence of effectiveness is lacking. Usual rehabilitation care is delivered by a multi-disciplinary team in the hospital and in the community. An 'enhanced rehabilitation' intervention has been developed consisting of a workbook, goal-setting diary and extra therapy sessions, designed to improve self-efficacy and increase the amount and quality of the practice of physical exercise and activities of daily living. METHODS/DESIGN: This paper describes the design of a phase II study comprising an anonymous cohort of all proximal femoral fracture patients admitted to the three acute hospitals in Betsi Cadwaladr University Health Board over a 6-month period with a randomised feasibility study comparing the enhanced rehabilitation intervention with usual care. These will assess the feasibility of a future definitive randomised controlled trial and concurrent economic evaluation in terms of recruitment, retention, outcome measure completion, compliance with the intervention and fidelity of delivery, health service use data, willingness to be randomised and effect size for a future sample size calculation. Focus groups will provide qualitative data to contribute to the assessment of the acceptability of the intervention amongst patients, carers and rehabilitation professionals and the feasibility of delivering the planned intervention. The primary outcome measure is function assessed by the Barthel Index. Secondary outcomes measure the ability to perform activities of daily living, anxiety and depression, potential mediators of outcomes such as hip pain, self-efficacy and fear of falling, health utility, health service use, objectively assessed physical function and adverse events. Participants' preference for rehabilitation services will be assessed in a discrete choice experiment. DISCUSSION: Phase II studies are an opportunity to not only assess the feasibility of trial methods but also to compare different methods of outcome measurement and novel methods of obtaining health service use data from routinely collected patient information. TRIAL REGISTRATION: Current Controlled Trials ISRCTN22464643, UKCRN16677.

Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function.

Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin-6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r = 0.9, P = 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments.

Patellar tendon properties and lower limb function in rheumatoid arthritis and ankylosing spondylitis versus healthy controls: a cross-sectional study.

OBJECTIVE: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) lead to inflammation in tendons and peritendinous tissues, but effects on biomechanical tendon function are unknown. This study investigated patellar tendon (PT) properties in stable, established RA and AS patients. METHODS: We compared 18 RA patients (13 women, 59.0 ± 2.8 years, mean ± SEM) with 18 age- and sex-matched healthy controls (58.2 ± 3.2 years), and 12 AS patients (4 women, 52.9 ± 3.4 years) with 12 matched controls (54.5 ± 4.7 years). Assessments with electromyography, isokinetic dynamometry, and ultrasound included quadriceps muscle force and cross-sectional area (CSA), PT stiffness, and PT CSA. Additionally, measures of physical function and disease activity were performed. RESULTS: PT stiffness and physical function were lower in RA and AS patients compared to healthy controls, without a significant difference in force production. PT CSA was significantly larger leading to reduction in Young's modulus (YM) in AS, but not in RA. CONCLUSION: The adverse changes in PT properties in RA and AS may contribute to their impaired physical function. AS, but not RA, leads to PT thickening without increasing PT stiffness, suggesting that PT thickening in AS is a disorganised repair process. Longitudinal studies need to investigate the time course of these changes and their response to exercise training.

A simple step test to estimate cardio-respiratory fitness levels of rheumatoid arthritis patients in a clinical setting.

Purpose. Exercise tests represent an important clinical tool to evaluate cardio-respiratory fitness and to predict future adverse cardiovascular events. However, use of such tests in patients with rheumatoid arthritis (RA) is relatively uncommon despite well-established evidence that low exercise capacity and high CVD mortality are features of this disease. Therefore, this study examined the validity and reliability of a sub-maximal step test for use in RA patients. Methods. Thirty patients (24 females) (mean ± SD age 53 ± 10 years) performed a sub-maximal step test on two occasions to estimate the criterion measure of cardio-respiratory fitness ([Formula: see text]). A further maximal cycling test provided a direct fitness measurement ([Formula: see text]). Pearson correlation coefficient, intraclass correlation coefficient (ICC), Bland and Altman plots, and 95% limits of agreement (LOA) were used to determine the validity and reliability of the sub-maximal test. Results. Estimated [Formula: see text] correlated well with directly measured [Formula: see text] (r = 0.79, LoA ±5.7 mL·kg(-1) ·min(-1)). Test-retest reproducibility for estimated [Formula: see text] was excellent (ICC = 0.97, LoA ±2.2 mL·kg(-1) ·min(-1)). Conclusion. The sub-maximal step test studied here represents a valid and reproducible method to estimate cardio-respiratory fitness in RA patients. This test may be useful for the assessment and management of CVD risk in a clinical setting.

Does proteinuria-inducing physical activity increase biomarkers of acute kidney injury?

AIM: We sought to determine if an acute kidney injury biomarker, neutrophil gelatinaseassociated lipocalin (NGAL), would be up-regulated by high-intensity proteinuria-inducing exercise. METHODS: A prospective cohort design was utilised. 100 healthy, active adults (mean age 24 ± 4 (SD) years) were screened for post-exercise proteinuria (PeP); 10 PeP positive and 10 PeP negative participants then completed a high-intensity exercise protocol involving an 800 meter sprint. Plasma and urinary NGAL, urinary creatinine, urinary albumin and urine volume were obtained at the following time points: pre-run, immediately post-, 25 minutes, one hour and two hours post-run. RESULTS: Following high-intensity exercise, 64% of participants had urinary NGAL concentrations above the normal range, particularly at 25 minutes post (P = 0.002). However, there was no difference in NGAL response between PeP positive and negative groups and plasma NGAL was decreased, not elevated, following exercise (P = 0.002). In some individuals normalizing urinary NGAL for urinary creatinine attenuated elevations. Urinary NGAL was also negatively correlated with urine volume (r = -0.701, P = 0.005). CONCLUSION: Proteinuria susceptibility did not influence an acute injury biomarker response to exercise. Nevertheless, urinary NGAL was elevated by exercise, possibly due to increased production by the proximal tubule, increased plasma clearance (given the decrease in plasma NGAL) and/or a concentrating effect of exercise-induced oliguria. Until correct normalisation of urinary biomarkers is determined, NGAL should be interpreted cautiously in exercise and acute kidney injury-induced oliguria. The inter-individual NGAL response to exercise also warrants further investigation.

An appraisal of rehabilitation regimes used for improving functional outcome after total hip replacement surgery.

This study aimed to systematically review the literature with regards to studies of rehabilitation programmes that have tried to improve function after total hip replacement (THR) surgery. 15 randomised controlled trials were identified of which 11 were centre-based, 2 were home based and 2 were trials comparing home and centre based interventions. The use of a progressive resistance training (PRT) programme led to significant improvement in muscle strength and function if the intervention was carried out early (< 1 month following surgery) in a centre (6/11 centre-based studies used PRT), or late (> 1 month following surgery) in a home based setting (2/2 home based studies used PRT). In direct comparison, there was no difference in functional measures between home and centre based programmes (2 studies), with PRT not included in the regimes prescribed. A limitation of the majority of these intervention studies was the short period of follow up. Centre based program delivery is expensive as high costs are associated with supervision, facility provision, and transport of patients. Early interventions are important to counteract the deficit in muscle strength in the affected limb, as well as persistent atrophy that exists around the affected hip at 2 years post-operatively. Studies of early home-based regimes featuring PRT with long term follow up are needed to address the problems currently associated with rehabilitation following THR.

Are the benefits of a high-intensity progressive resistance training program sustained in rheumatoid arthritis patients? A 3-year followup study.

OBJECTIVE: Rheumatoid arthritis (RA) patients were reassessed for body composition and physical function mean ± SD 39 ± 6 months after commencing a randomized controlled trial involving 24 weeks of either high-intensity progressive resistance training (PRT) or low-intensity range of movement exercise (control) to determine whether the benefits of PRT (i.e., reduced fat mass [FM], increased lean mass [LM], and improved function) were retained. METHODS: Nine PRT and 9 control subjects were reassessed for body composition (dual x-ray absorptiometry) and function (knee extensor strength, chair test, arm curl test, 50-foot walk) approximately 3 years after resuming normal activity following the exercise intervention. RESULTS: At followup, PRT subjects remained significantly leaner than control subjects (P = 0.03), who conversely had accumulated considerable FM during the study period (approximately -1.0 kg versus +2.4 kg, PRT versus controls). PRT subjects also retained most of the improvement in walking speed gained from training (P = 0.03 versus controls at followup). In contrast, the PRT-induced gains in LM and strength-related function were completely lost. Data from the controls suggest that established and stable RA patients have similar rates of LM loss but elevated rates of FM accretion relative to age-matched sedentary non-RA controls. CONCLUSION: We found that long-term resumption of normal activity resulted in loss of PRT-induced improvements in LM and strength-related function, but substantial retention of the benefits in FM reduction and walking ability. The relatively long-term benefit of reduced adiposity, in particular, is likely to be clinically significant, as obesity is very prevalent among RA patients and is associated with their disability and exacerbated cardiovascular disease risk.

Benefits of exercise in rheumatoid arthritis.

This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, "rheumatoid cachexia". These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training.

Skeletal muscle properties in rheumatoid arthritis patients.

PURPOSE: Disability in patients with rheumatoid arthritis (RA) is a multifactorial process involving various unaccounted factors. Loss of lean body mass plays an important role in impaired physical function, and exercise studies in RA have shown promising results in restoring muscle mass, strength, and function. However, no comprehensive assessment of the muscle characteristics has been undertaken to determine whether qualitative changes in muscle also contribute to RA disability. This study explores the physiological muscle properties of a community-based population with stable RA. METHODS: Vastus lateralis (VL) force and physiological cross-sectional area (PCSA), voluntary muscle activation capacity, and contractile properties were assessed in 23 patients with stable RA (age = 60 ± 2 yr (mean ± SEM); 16 women) and age- and sex-matched healthy controls (age = 60 ± 3 yr). Measurements with EMG were obtained during maximal isometric knee extension contractions, with resting and superimposed electrical stimulations. Concentric knee extension contractions were also assessed. Pennation angle and VL volume were measured with ultrasound to determine fiber fascicle length and PCSA. Muscle-specific force was calculated (VL force/VL PCSA). Body composition using dual-energy x-ray absorptiometry and objective physical function were also measured. RESULTS: The patients displayed typical features of RA with reduced physical function (P = 0.001-0.09), a trend toward lower appendicular lean mass (P = 0.09) and increased total body fat (P < 0.05) relative to controls. However, there were no differences in specific force, contractile properties, voluntary activation capacity, and contraction velocity (P = 0.41-0.99). VL PCSA was reduced (P < 0.05) with minor architectural changes in patients with RA. CONCLUSIONS: Physiological properties of muscle that determine specific force are not compromised in patients with stable RA despite deficits in physical function.

Muscle quality, architecture, and activation in cachectic patients with rheumatoid arthritis.

OBJECTIVE: To explore muscle-specific force (force per physiological cross-sectional area, or PCSA) and muscle activation in cachectic patients with rheumatoid arthritis (RA). METHODS: In 14 muscle-wasted patients with RA and age and sex matched healthy controls, vastus lateralis (VL) force and voluntary activation capacity were assessed during maximal isometric contractions with electromyography and superimposed electrical stimulations. VL PCSA was determined from ultrasound measures of fiber fascicle length (Lf), pennation angle, and volume, together with assessments of body composition by dual energy x-ray absorptiometry and objective physical function. RESULTS: Although patients with RA had reduced physical function, lower muscle mass, and VL volume relative to controls, there were no differences in muscle-specific force and activation. PCSA, force, and pennation angle tended to be lower in RA, with no differences in Lf. CONCLUSION: Muscle-specific force and activation are not compromised and thus are unlikely to contribute to reduced function in cachectic patients with RA.

Effects of high-intensity resistance training in patients with rheumatoid arthritis: a randomized controlled trial.

OBJECTIVE: To confirm, in a randomized controlled trial (RCT), the efficacy of high-intensity progressive resistance training (PRT) in restoring muscle mass and function in patients with rheumatoid arthritis (RA). Additionally, to investigate the role of the insulin-like growth factor (IGF) system in exercise-induced muscle hypertrophy in the context of RA. METHODS: Twenty-eight patients with established, controlled RA were randomized to either 24 weeks of twice-weekly PRT (n = 13) or a range of movement home exercise control group (n = 15). Dual x-ray absorptiometry-assessed body composition (including lean body mass [LBM], appendicular lean mass [ALM], and fat mass); objective physical function; disease activity; and muscle IGFs were assessed at weeks 0 and 24. RESULTS: Analyses of variance revealed that PRT increased LBM and ALM (P < 0.01); reduced trunk fat mass by 2.5 kg (not significant); and improved training-specific strength by 119%, chair stands by 30%, knee extensor strength by 25%, arm curls by 23%, and walk time by 17% (for objective function tests, P values ranged from 0.027 to 0.001 versus controls). In contrast, body composition and physical function remained unchanged in control patients. Changes in LBM and regional lean mass were associated with changes in objective function (P values ranged from 0.126 to <0.0001). Coinciding with muscle hypertrophy, previously diminished muscle levels of IGF-1 and IGF binding protein 3 both increased following PRT (P < 0.05). CONCLUSION: In an RCT, 24 weeks of PRT proved safe and effective in restoring lean mass and function in patients with RA. Muscle hypertrophy coincided with significant elevations of attenuated muscle IGF levels, revealing a possible contributory mechanism for rheumatoid cachexia. PRT should feature in disease management.

Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study.

BACKGROUND/AIMS: In patients with chronic kidney disease (CKD) receiving adequate erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance muscle mass is not known. METHODS: In this phase II dose-finding study, 54 patients with CKD stage 5 were randomized to either low, medium or high doses of ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in females), while 7 patients acted as non-randomized controls. The primary outcome measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry. Fluid overload (hydration of the fat-free mass) and indicators of physical functioning were secondary measures. Harms were also recorded. Data were analysed using Quade's (1967) non-parametric analysis of covariance. RESULTS: ND increased ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs. 1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups, respectively, p < 0.001) with no increases in fluid overload but no consistent effect on physical functioning. The highest dose of ND (100 mg/week) was intolerable in females because of virilizing effects. CONCLUSION: If goals of future studies are to improve body composition, dosing of ND up to 200 mg/week in males and 50 mg/week in females should be investigated. However, to realize improvements in physical functioning, future phase III trials of ND may require additional interventions such as exercise training.

Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis.

BACKGROUND: Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans. OBJECTIVE: The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA). DESIGN: Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study. RESULTS: Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function. CONCLUSIONS: Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.