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.

The frequency and outcome of lupus nephritis: results from an international inception cohort study.

OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. RESULTS: There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. CONCLUSION: LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN.

Does an early home-based progressive resistance training program improve function following total hip replacement? Results of a randomized controlled study.

BACKGROUND: In-hospital progressive resistance training (PRT) has been shown to be an effective method of rehabilitation following hip surgery. The aim of this study was to assess whether a home-based PRT program would be beneficial in improving patients' muscle strength and physical function compared to standard rehabilitation. METHODS: Subjects (n = 49) either received home-based PRT rehabilitation (n = 25) or standard rehabilitation (n = 24) in a prospective single blinded randomized trial carried out over a two-year period. The primary outcome measure was the maximal voluntary contraction of the operated leg quadriceps (MVCOLQ) with secondary measures of outcome being the sit to stand score (ST), timed up and go (TUG), stair climb performance (SCP), the 6 min walk test (6MWT), and lean mass of the operated leg (LM). RESULTS: Twenty-six patients completed follow up at 1 year (n = 13 per group) for the final comparative analysis. All the outcome measures showed marked progressive improvements from the baseline measures at 9-12 months post op (Estimated effect (std error); p value)- MVCOLQ 26.50 (8.71) N p = 0.001; ST 1.37 (0.33) p = 0.0001; TUG -1.44 (0.45) s p =0.0001; SCP -3.41(0.80)s p = 0.0001; 6MWT 45.61 (6.10)m p = 0.0001; LM 20 (204)g p = 0.326) following surgery for both groups. Overall, there was no significant effect for participation in the exercise regime compared with standard care for all outcomes assessed. CONCLUSIONS: Overall, this study demonstrated that there is no significant difference between the two groups for participation in the home-based PRT exercise programme when compared to standard care for all outcomes. TRIAL REGISTRATION: ISRCTN 1309951. Registered February 2011.

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. METHODS: The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. RESULTS: Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). CONCLUSION: The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies.

What does standard rehabilitation practice after total hip replacement in the UK entail? Results of a mixed methods study.

BACKGROUND: There is evidence of prolonged poor function in patients following total hip replacement (THR). Studies of progressive resistance training (PRT) interventions to improve function are often compared to 'standard' practice which is not well defined. This study aimed to investigate 'standard' rehabilitation care in the UK after total hip replacement (THR) as well as determine whether PRT was part of 'standard' care. METHODS: After ethical approval, questionnaire item development about rehabilitation practice was guided by a focus group interview (after informed consent) with physiotherapists (n = 4; >5 years post-qualification) who regularly treated THR patients. An online questionnaire investigating the exercises prescribed and rehabilitation practice following THR was developed and sent to physiotherapists working in hospitals in the UK. The survey was performed from January to May 2011. The survey results were analysed (frequency (%) of responses) focusing on the exercises the physiotherapists considered important, as well as their use of PRT in prescribed regimes. RESULTS: 106 responses were obtained from physiotherapists in the UK. The survey respondents considered that the most important muscles to target in all phases of rehabilitation were the hip abductors (62.2%), followed by the quadriceps (16.9%), and other muscles (21%). Exercise type prescribed revealed no consensus, with weight bearing (42%), functional (45%) and Bed-based/Bridging/Postural exercises (13%) favoured. 83.7% were able to define the basis of progressive resistance training (PRT), but only 33% prescribed it. CONCLUSIONS: Standard physiotherapy rehabilitation in the UK after THR is variable, and appears to rarely include PRT. This may be a factor in prolonged poor function in some patients after this common operation.

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.

Baseline vWF factor predicts the development of elevated pulmonary artery pressure in systemic sclerosis.

OBJECTIVES: This study aims to examine the utility of von Willebrand factor (vWF) as a biomarker in lcSSc, in particular the ability of vWF to predict the future development of disease manifestations in this disease. METHODS: vWFAg concentrations were measured in the serum of patients with lcSSc at baseline and at 3 years, during the QUINs trial [Prevention of Vascular Damage in Scleroderma with Angiotensin-Converting Enzyme (ACE) Inhibition]. %DL(CO), %KCO, %FVC, pulmonary artery pressure (PAP) estimation by echocardiography, Raynaud's attack frequency, Raynaud's severity, digital ulcer frequency, urinary protein excretion, estimated glomerular filtration rate (eGFR), modified Rodnan skin score and Medsger disease activity score were also measured at baseline and 3 years. RESULTS: Baseline serum vWF concentrations were related to concurrent Medsger disease activity score, %DL(CO), %FVC, urinary protein excretion, eGFR and PAP >30 mmHg. In logistic regression models, baseline serum vWF concentrations were able to predict the future development of elevated PAP by echocardiography (PAP >40 mmHg, P = 0.001). CONCLUSIONS: Pulmonary artery hypertension is a life-threatening complication of lcSSc. vWF is a marker of endothelial cell activation. Raised serum concentrations of vWF in lcSSc increase the risk of developing subsequent elevation in PAP. Therefore screening patients with lcSSc for vWF may identify a group at risk of developing PAH. These patients could potentially be targeted with agents that stabilize the endothelium, e.g. statins.

A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.

OBJECTIVE: MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA. METHODS: A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores). RESULTS: Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events. CONCLUSIONS: This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA. Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151.

Perceptions of the effects of exercise on joint health in rheumatoid arthritis patients.

OBJECTIVES: Exercise is important in RA management. However, RA patients are less active than the general population. This qualitative study explores the perceptions of patients regarding the effects of exercise on joint health. METHODS: A purposive sample of 12 female and 6 male RA outpatients [age: 23-76 years; disease duration: 2.5 months to 33 years; HAQ score: 0-2.13] participated in four moderated focus groups. The main questions addressed were: (i) How do you feel exercise affects your joints?; and (ii) What affects your exercise behaviour? Transcriptions were independently analysed with 455 meaning units identified. An inductive, thematic analysis was conducted using established techniques. Discussion with a third analyst contributed to consensus validation. RESULTS: Sixteen constructs emerged, clustering into five themes, reflecting the issues relating to exercise and joint health in RA patients. Emergent themes were: 'health professionals showing a lack of exercise knowledge', 'not knowing what exercise should be done', 'worry about causing harm to joints', 'not wanting to exercise as joints hurt' and 'having to exercise because it is helpful'. CONCLUSIONS: RA patients demonstrated awareness of the advantages of exercise for their joints, both experientially and through education. However, they perceived that health professionals lacked certainty and clarity regarding specific exercise recommendations and the occurrence of joint damage. Thus, to enhance patient-centred exercise prescription in the RA population, uncertainties surrounding joint health, pain symptoms and exercise specificity need to be addressed, alongside continual emphasis of exercise benefits.

The BILAG multi-centre open randomized controlled trial comparing ciclosporin vs azathioprine in patients with severe SLE.

OBJECTIVE: To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE. METHODS: Patients with SLE requiring a change or initiation of a corticosteroid-sparing agent and who were taking > or =15 mg of prednisolone/day were randomized to receive either ciclosporin or AZA during this 12-month open-label multi-centre trial. There were strict guidelines for the reduction of prednisolone. The primary outcome was the absolute mean change in prednisolone. RESULTS: Eighty-nine patients were randomized. Using an intention-to-treat analysis, the absolute mean change in prednisolone dose between baseline and 12 months, adjusted for baseline prednisolone dose, was 9.0 mg for ciclosporin (95% CI 7.2, 10.8) and 10.7 mg for AZA (95% CI 8.8, 12.7). The difference in the change between treatment groups was -1.7 mg (95% CI -4.4, 0.9; P = 0.2). No significant differences were detected for the secondary outcomes: change in disease activity [classic British Isles Lupus Assessment Group (BILAG) index], number of flares, development of new damage or change in quality of life. A similar number of patients in each arm stopped the study drugs due to adverse events and ineffectiveness. No patient developed severe hypertension or a persistent rise in creatinine. One patient in the ciclosporin arm developed a significant increase in proteinuria due to disease activity. CONCLUSIONS: Both drugs were effective corticosteroid-sparing agents. Ciclosporin was not a more effective corticosteroid-sparing agent. Ciclosporin may be considered in patients who are unable to tolerate AZA. Patients on ciclosporin require close monitoring of blood pressure and creatinine. TRIAL REGISTRATION: Current Controlled Trials, http://www.controlled-trials.com/, ISRCTN35919612.

Impact of primary Sjogren's syndrome on smell and taste: effect on quality of life.

OBJECTIVES: To assess the prevalence of abnormal smell and taste perception in people with primary SS and the effect on quality of life (QoL). METHODS: Twenty-eight participants with SS and 37 controls were enrolled in a cohort-matched, prospective, cross-sectional study. Smell and taste thresholds were measured using standardized, validated tests. QoL was assessed by the Short Form 12 (SF-12). RESULTS: Smell threshold was reduced by 1 point (P = 0.002; 95% CI 0.35, 1.54) and taste threshold was reduced by 3.5 points (P < 0.001; 95% CI 1.80, 5.22) in the SS group compared with controls. The physical and mental components of SF-12 were reduced by 14.2 points (P < 0.001; 95% CI 9.47, 19.02) and 7.5 points (P = 0.002; 95% CI 2.97, 12.02), respectively, in the SS group compared with controls. Taste threshold was significantly correlated with both the physical (r = 0.48; P < 0.001) and the mental (r = 0.30; P = 0.015) components of SF-12. Smell threshold correlated with the physical (r = 0.457; P < 0.001), but not the mental component (r = 0.154; P = 0.222) of SF-12. CONCLUSIONS: Clinically important impairment of chemosensory perception occurred in the SS group compared with age- and gender-matched controls. Assessment using SF-12 suggests that this impairment contributed to the reduced health-related QoL that characterized these individuals.

The BILAG-2004 index is sensitive to change for assessment of SLE disease activity.

OBJECTIVE: To determine if the BILAG-2004 index is sensitive to change for assessment of SLE disease activity. METHODS: This was a prospective multi-centre longitudinal study of SLE patients. At every assessment, data were collected on disease activity (BILAG-2004 index) and treatment. Analyses were performed using overall BILAG-2004 index score (as determined by the highest score achieved by any of the individual systems) and all the systems scores. Sensitivity to change was assessed by determining the relationship between change in disease activity and change in therapy between two consecutive visits. Statistical analyses were performed using multinomial logistic regression. RESULTS: There were 1761 assessments from 347 SLE patients that contributed 1414 observations for analysis. An increase in therapy between visits occurred in 22.7% observations, while 37.3% had a decrease in therapy and in 40.0% therapy was unchanged. Increase in overall BILAG-2004 index score was associated with increase in therapy and inversely associated with decrease in therapy. Decrease in overall BILAG-2004 index score was associated with decrease in therapy and was inversely associated with increase in therapy. Changes in overall BILAG-2004 index score were differentially related to change in therapy, with greater change in score having greater predictive power. Increase in the scores of most systems was independently associated with an increase in treatment and there was no significant association between decreases in the score of any system with an increase in therapy. CONCLUSIONS: The BILAG-2004 index is sensitive to change and is suitable for use in longitudinal studies of SLE.

Numerical scoring for the Classic BILAG index.

OBJECTIVE: To develop an additive numerical scoring scheme for the Classic BILAG index. METHODS: SLE patients were recruited into this multi-centre cross-sectional study. At every assessment, data were collected on disease activity and therapy. Logistic regression was used to model an increase in therapy, as an indicator of active disease, by the Classic BILAG score in eight systems. As both indicate inactivity, scores of D and E were set to 0 and used as the baseline in the fitted model. The coefficients from the fitted model were used to determine the numerical values for Grades A, B and C. Different scoring schemes were then compared using receiver operating characteristic (ROC) curves. Validation analysis was performed using assessments from a single centre. RESULTS: There were 1510 assessments from 369 SLE patients. The currently used coding scheme (A = 9, B = 3, C = 1 and D/E = 0) did not fit the data well. The regression model suggested three possible numerical scoring schemes: (i) A = 11, B = 6, C = 1 and D/E = 0; (ii) A = 12, B = 6, C = 1 and D/E = 0; and (iii) A = 11, B = 7, C = 1 and D/E = 0. These schemes produced comparable ROC curves. Based on this, A = 12, B = 6, C = 1 and D/E = 0 seemed a reasonable and practical choice. The validation analysis suggested that although the A = 12, B = 6, C = 1 and D/E = 0 coding is still reasonable, a scheme with slightly less weighting for B, such as A = 12, B = 5, C = 1 and D/E = 0, may be more appropriate. CONCLUSIONS: A reasonable additive numerical scoring scheme based on treatment decision for the Classic BILAG index is A = 12, B = 5, C = 1, D = 0 and E = 0.

Health Professionals' Perceptions of the Effects of Exercise on Joint Health in Rheumatoid Arthritis Patients.

OBJECTIVES: Although exercise is an important factor in the management of rheumatoid arthritis (RA), research indicates that patients perceive that health professionals (HPs) are uncertain about the place of exercise in treatment and its relationship with joint damage. The present study investigated the perceptions of HPs regarding the effects of exercise on joint health in RA patients. METHODS: A questionnaire investigating perceptions of exercise and joint health was distributed via professional networks and websites. Confirmatory factor analysis (CFA) was used to analyse questionnaire data and develop a focus group interview guide. Focus groups were conducted with multidisciplinary teams (MDTs) of rheumatology HPs and analysed using framework analysis. RESULTS: A total of 137 rheumatology HPs (95 female; 27-65 years of age) completed questionnaires. CFA showed that a four-factor model provided a marginally acceptable fit. Analysis of four focus groups (n = 24; 19 female; 30-60 years of age) identified five themes relating to HPs' perceptions of exercise and joint health in RA patients: 'Exercise is beneficial', 'Concerns about damage to joints', 'Patients have barriers to exercise', 'HP knowledge differs' and 'Patients may think service delivery is vague'. CONCLUSIONS: HPs were highly aware of the benefits and importance of exercise for RA patients. However, to remove the patient perception that HPs lack certainty and clarity regarding exercise it is important to ensure: (i) consistent promotion of exercise across the whole MDT; (ii) clear provision of information regarding rest, joint protection and exercise; (iii) HP education to ensure consistent, accurate knowledge, and understanding of the potential for conflicting advice when promoting exercise as part of an MDT. Copy © 2016 John Wiley & Sons, Ltd.

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.

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.

Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial.

BACKGROUND & AIMS: Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of beta-hydroxy-beta-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia. METHODS: Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. RESULTS: Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (groupxtime interactions P>0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727+/-1186 g, P<0.01), total body protein (719+/-1703 g, P=0.02), arms (112+/-183 g, P<0.01) and legs (283+/-534 g, P<0.01) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. CONCLUSIONS: Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.

The Effects of Aerobic and Resistance Exercise on Markers of Large Joint Health in Stable Rheumatoid Arthritis Patients: A Pilot Study.

OBJECTIVE: Exercise is beneficial for people with rheumatoid arthritis (RA). However, patients and health professionals have expressed concern about the possible detrimental effects of exercise on joint health. The present study investigated the acute and chronic effects of high-intensity, low-impact aerobic and resistance exercise on markers of large joint health in RA. METHODS: Eight RA patients and eight healthy, matched control (CTL) participants performed 30 minutes' high-intensity, low-impact aerobic and lower-body resistance exercise, one week apart. Primary outcome measures assessing joint health were serum cartilage oligomeric matrix protein (sCOMP) and knee joint synovial inflammation (Doppler ultrasound colour fraction; CF). These measures were taken at baseline, immediately after and 0.5, one, two, six and 24 hours post-exercise. In a separate study, nine RA patients completed eight weeks of progressive exercise training. The same outcome measures were reassessed at baseline, and at one hour post-exercise of training weeks 0, 1, 4 and 8. RESULTS: RA patients showed higher overall sCOMP [RA: 1,347 ± 421, CTL: 1,189 ± 562 ng/mL; p < 0.05; effect size (ES) = 0.32] and CF when scanned longitudinally (RA: 0.489 ± 0.30 × 10(-3) , CTL: 0.101 ± 0.13 × 10(-3) ; p < 0.01; ES = 1.73) and transversely (RA: 0.938 ± 0.69 × 10(-3) , CTL: 0.199 ± 0.36 × 10(-3) ; p < 0.01; ES = 1.33) than CTL. However, no acute effects on joint health were observed post-exercise. Similarly, no chronic effects were observed over eight weeks of combined aerobic and resistance training in RA, with positive effects on physical fitness and function. CONCLUSIONS: RA patients on stable treatment with low disease activity were able to perform an individually prescribed high-intensity, low-impact aerobic and resistance exercise without changes in markers of large joint health. Copyright © 2015 John Wiley & Sons, Ltd.

Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

OBJECTIVE: To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. DESIGN: Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. SETTING: 24 rheumatology clinics in England. PARTICIPANTS: Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. INTERVENTIONS: Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. PRIMARY OUTCOME: reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. SECONDARY OUTCOMES: quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. RESULTS: 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was -0.14, and the 95% confidence interval (-0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (€4930, $5585) for months 0-6 and £1930 for months 6-12. CONCLUSIONS: In patients with active rheumatoid arthritis who meet English criteria for biologics an alternative strategy with combinations of intensive synthetic disease modifying drugs gives non-inferior outcomes to treatment with tumour necrosis factor inhibitors. Costs are reduced substantially.Trial Registration ISRCTN 37438295.

Is it SLE?

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease, as yet of unknown aetiology, with diverse clinical manifestations and a variable course and prognosis. The diagnosis is based on recognizing the overall pattern of clinical and laboratory abnormalities. However, even today, there is often a significant delay between onset of symptoms and diagnosis. Over the last two decades there has been great progress in identifying the profile of antinuclear antibodies that characterizes SLE, and in this chapter we describe how serological techniques can be important tools for the clinician in the early diagnosis of this disorder. Also described is the lupus band test, which has rather fallen out of favour as a diagnostic tool but which can still provide valuable evidence for the diagnosis in patients in whom the clinical and serological features are inconclusive. Nevertheless, because the presentation of lupus is protean, and the early manifestations are often non-specific, SLE can still be easily confused with a wide range of other conditions. Here, we describe some of the common clinical conundrums encountered in patients referred to the Lupus Clinic to 'rule out lupus', providing a framework for diagnosis. Finally, the chapter considers the major problem that clinicians who treat patients with SLE frequently face in distinguishing between a flare of lupus and infection. Diagnosis of SLE is still a great clinical challenge, and while it is important to recognize patients with potentially aggressive disease and treat them appropriately at an early stage it is also important to be able to recognize patients with potentially benign disease and avoid over-treatment.