Summary Background Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have ...directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis. Methods This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score DAS28-ESR >3·2; rituximab group) or a TNF inhibitor—adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0·6 DAS28-ESR units. This study is registered with ClinicalTrials.gov , number NCT01021735. Findings Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was −2·6 (SD 1·4) and TNF inhibitor was −2·4 (SD 1·5), with a difference within the prespecified non-inferiority margin of −0·19 (95% CI −0·51 to 0·13; p=0·24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (£9405 vs £11 523 per patient, p<0·0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0·5462). One patient in each group died during the study. Interpretation Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months. Funding Arthritis Research UK, Roche.
There is no agreement among the rheumatology community in how to implement the musculoskeletal ultrasound (MSUS) technique in the Rheumatology Divisions. To test the perceived usefulness of the MSUS, ...under consensus indications, for referring colleagues for the clinical management of their patients with inflammatory arthritis (IA) and to score the satisfaction level of the patients with different aspects of the ultrasound (US) examination, after attend to the MSUS clinic. A written questionnaire-based survey regarding the usefulness and satisfaction with the implementation of a pilot MSUS clinic in a Rheumatology Unit. Over a 6-month period, 43 patients attended 10 MSUS clinics. Referral agreed indications were: US assisting in early/subclinical diagnosis (35 %), decision making with patient treatment (44 %), monitoring of disease activity/treatment response (39 %) and US-guided injection (11 %). Average scores of the referrers regarding usefulness of the information provided for the US for these indications were 8.0, 8.3, 8.7 and 8.6, respectively, with a high score of 9.0 regarding the valuable support of the US for the management of their patients with IA. Patient satisfaction scores in responders (44 %) were averaged 9.5 and higher for receiving an adequate explanation of the US procedure, indications, US findings and their significance, lack of discomfort and length of the appointment. The average score was slightly lower (8.5) for the waiting time frame for the appointment for the MSUS examination. The referrers expressed a perception of usefulness of our pilot US clinic, under previous consensus indications, for the clinical management of their patients with IA. In addition, this MSUS clinic seemed to show a good acceptability and a high satisfaction scores for the patients.
The aim of the study was to assess agreement between three-dimensional volumetric ultrasound (3D US) performed by inexperienced staff and real-time conventional ultrasound (2D US) performed by ...experienced rheumatologists in detecting and scoring rheumatoid arthritis (RA) lesions. Thirty-one RA patients underwent examination of seven joints by 2D and 3D US for synovitis and tenosynovitis in B and PD modes and erosions in B mode. A global score for synovitis and global counts for synovitis, tenosynovitis and erosions were also calculated for every patient. Agreement between 2D and 3D US was analysed for counts and scores at the patient level with the intraclass correlation coefficient (ICC) and for counts at the joint level with Cohen’s kappa coefficient. B-mode synovitis was detected at a median of five joints in each patient, frequently in wrists and hand joints but less frequently in foot joints. PD-mode synovitis, tenosynovitis and erosions were detected less frequently. All ICCs for agreement between 2D and 3D US findings were significant. All kappa coefficients were significant for B- and PD-mode synovitis and for erosions (except PIP3), while those for tenosynovitis were only significant for MCP2 (B and PD modes) and PIP2 (B mode). Although the 3D US volumes were acquired by inexperienced operators, agreement between 2D and 3D US was acceptable in detecting and scoring synovitis. A higher level of agreement was attained for patient-level global scores and counts than for individual joints.
Abstract
Objectives
Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally ...quantify, characterize and contextualize infection risk in AAV.
Methods
We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.
Results
A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9–5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio IRR 7.3 95% confidence interval (CI) 5.6, 9.6; severe infections: IRR 4.4 95% CI 3.3, 5.7; antibiotic prescriptions: IRR 2.2 95% CI 1.9, 2.6}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes IRR 12.5 (95% CI 3.7, 42.6) and Candida IRR 11.4 (95% CI 2.4, 55.4).
Conclusion
AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.
Abstract
Objectives
Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor ...apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response.
Methods
We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis. Cardiometabolic, anthropometric and disease activity assessments were performed at baseline (pre-apremilast) and at months 1, 3 and 6 of apremilast treatment in 60 patients. A subgroup underwent further assessment of endothelial function, body composition and adipocyte morphology.
Results
In patients (median age 54.5 years, 63% women, median BMI 33.2 kg/m2), apremilast was associated with a mean weight loss of 2.2 kg (95% CI 1.4, 3.0; P < 0.001) and a mean BMI decrease of 0.8 kg/m2 (95% CI 0.5, 1.2; P < 0.001) after 6 months of treatment. Body composition analysis demonstrated a reduction in total abdominal fat mean decrease 0.52 L (95% CI 0.08, 0.96), P = 0.022, principally subcutaneous adipose tissue mean decrease 0.37 L (95% CI 0.05, 0.68), P = 0.022. There was no change in adipocyte diameter, haemoglobin A1c, lipid, glucagon-like peptide-1 or vascular function. Psoriatic disease activity improved with apremilast, although this was not correlated with weight change.
Conclusion
Following apremilast treatment, we observed weight loss, principally abdominal subcutaneous fat, and improvement in psoriatic disease activity. The latter was independent of weight change, suggesting apremilast likely acts through direct immunological mechanisms.
Objective
To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support ...early patient education and decision‐making.
Methods
The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire HAQ score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool.
Results
Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio OR 2.67 95% confidence interval (95% CI) 1.98, 3.59), depression (OR 2.52 95% CI 1.18, 5.37), anxiety (OR 2.37 95% CI 1.33, 4.21), being in paid employment with absenteeism during the last week (OR 1.19 95% CI 0.63, 2.23), not being in paid employment (OR 2.36 95% CI 1.38, 4.03), and being overweight (OR 1.61 95% CI 1.04, 2.50). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31).
Conclusion
In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability.
Abstract
Objectives
The aim was to describe a modern National Health Service (NHS) Scotland cohort of patients with GCA over 12 months of care to include clinical presentation, practices relating to ...assessment and treatment, and specifically, the use of tocilizumab.
Methods
A multicentre audit of patients newly diagnosed with GCA between November 2019 and October 2021 was established on behalf of the Scottish Society for Rheumatology. Clinical data were collected retrospectively by rheumatology teams at participating NHS centres using electronic patient records. An extended cohort of patients from NHS Lothian was examined to investigate outcomes of tocilizumab use for >1 year.
Results
Sixty-three patients from three NHS Scotland health boards were included, with analysis of data from 216 clinic episodes. Mean follow-up was 371 days. Mean age was 71 years; 62% were female. The most common presenting features were headache (93.6%), scalp tenderness (82.5%) and ocular symptoms (24%). At baseline, 63% of patients had at least one existing risk factor for adverse outcomes from high-dose CS use, namely hypertension (57.1%), diabetes (24%) and osteoporosis (11%). Thirty per cent of all patients (19 of 63) received tocilizumab, with only 11% (7 of 63) receiving tocilizumab owing to glucocorticoid risk factors at baseline. One-quarter of all patients (16 of 63) experienced relapse of GCA during follow-up, of whom six were subsequently treated with tocilizumab.
Conclusion
This multicentre audit demonstrates that despite its availability for patients with risk factors for CS adversity and those who suffer relapse of GCA, tocilizumab is used in less than one-quarter of patients who might benefit. The reasons for this require further exploration.
PDF
