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Objectives: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients., Methods: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates., Results: 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59)., Conclusions: Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.

Objectives: Counting the number of tender and swollen joints is an important aspect of assessing patients with an inflammatory arthritis. We provide a comprehensive overview of joint counts in inflammatory arthritis. This spans how they are undertaken, their use in clinical and research settings, their limitations and standardisation and who can perform them., Methods: We reviewed the literature surrounding joint counts in inflammatory arthropathies, with a specific focus on rheumatoid arthritis (RA)., Results: The current widely used joint count assesses 28 peripheral joints. In RA these are usually incorporated in a composite score of disease activity, termed the disease activity score on a 28-joint count (DAS28). Assessing 28 joints has a strong 'floor-effect' with most patients in routine practice having low swollen and tender joint counts. Marked between-observer variation exists in joint count scores; although the variation in tender joint counts can be reduced by standardised training its impact on swollen joint counts is uncertain. Fibromyalgia can have a marked impact on tender joint count scores, resulting in a disproportionately high tender joint count to swollen joint count ratio. Although there is evidence that patient-assessed tender joint counts correlate well with those undertaken by physicians, patients are limited assessors of synovitis., Conclusions: Although joint counts provide an important objective measure of disease activity in clinical practice, they have a number of limitations. Future research may provide a more robust clinical assessment for disease activity in inflammatory arthropathies, which overcomes these issues.

Objectives: When rheumatoid arthritis (RA) patients have achieved sustained good clinical responses can their disease-modifying anti-rheumatic drugs (DMARDs) be reduced or discontinued? This review addresses this question by summarising the clinical evidence about DMARD withdrawal. It includes an assessment of predictive factors for sustained DMARD-free remissions., Methods: We evaluated the evidence for discontinuing DMARDs in stable RA in both randomised controlled trials (RCTs) and observational studies., Results: Six RCTs evaluated DMARD monotherapy withdrawal in 501 RA patients with good clinical responses. Flares occurred in 43/248 (17%) patients who continued DMARD monotherapy and in 117/253 (46%) patients who discontinued DMARDs. Individuals in whom DMARDs were withdrawn were three times more likely to have flares. Restarting DMARDs post-flare was usually successful. Four RCTs evaluated step-down DMARD combinations in comparison to DMARD monotherapy. Patients achieved good clinical responses with combination DMARDs, which were maintained after treatment was tapered to DMARD monotherapy. Four observational studies of tapering or stopping DMARDs in patients with sustained low disease activity states provided supportive evidence for discontinuing DMARDs in some patients. Flares during drug-free remissions were predicted by rheumatoid factor and anti-citrullinated protein antibody status., Conclusions: Drug-free remission is achievable in some RA patients. Discontinuation of DMARDs after patients achieve sustained remissions results in flares in many patients, which can usually be reversed by restarting DMARDs. Step-down DMARD combinations are effective and achieve sustained responses. Further research is required to establish predictors of drug-free remission; these will identify individuals most likely to benefit or experience disease flares after discontinuing DMARDs.

Objectives: Delivering treat-to-target strategies in rheumatoid arthritis (RA) involves commitments from both providers and payers for healthcare. We have summarised the perspectives of payers from England, where the National Health Service (NHS) provides universal care that is without cost for patients., Methods: We reviewed the literature - including that from the NHS and National Institute for Health and Clinical Excellence (NICE) - concerning payers views on the clinical effectiveness and cost-effectiveness of treat-to-target strategies for RA., Results: Commissioners pay for government-funded English healthcare and providers (divided between General Practitioners (GPs) and Hospital Consultants) and deliver it according to NICE guidance. Treat-to-target using intensive disease-modifying drug (DMARD) combinations with glucocorticoids are recommended for early active RA. Treatment tapering is recommended when disease control is achieved. Some aspects of treat-to-target are recommended in established RA, including the early management of flares and the use of biologics in persistently active RA that is non-responsive to DMARDs. However, treat-to-target is not widely recommended in established RA, mainly because the evidence base is incomplete. English healthcare is moving towards quality care becoming the main driver and is adopting 'integrated care' involving both GPs and consultants for most long-term disorders; RA is likely to be included within these approaches, which are unlikely to focus specifically on treat-to-target., Conclusions: Payers strongly support treat-to-target in early RA. In established disease there is limited enthusiasm; without stronger evidence for efficacy and cost-effectiveness this is unlikely to change.

Objectives: Rheumatoid arthritis (RA) is associated with excess cardiovascular (CV) disease. Many studies have shown subclinical atherosclerosis in RA is associated with CV risk factors and inflammation. Their relationship with CV events has however received less attention. Furthermore, except for hypertension CV risk factor management has not been examined in a UK RA population. We therefore evaluated the contribution of RA specific and CV risk factors to CV events alongside the management of CV risk factors in RA patients., Methods: We assessed the prevalence, screening and treatment of CV risk factors in a cross-sectional survey of RA patients consecutively attending specialist clinics. We used binary logistic regression to examine relationships between CV events and RA and CV risk factors., Results: We enrolled 309 patients (81% female; median age 60 years; median disease duration 8 years). 27 (9%) had previous CV events. 56% had hypertension, 42% hyperlipidaemia, 11% diabetes, 52% were ex/current smokers and 26% obese. Lipid status was unknown in one third. 47% of patients on anti-hypertensive agents were undertreated. CV events were associated with hyperlipidaemia (OR 13.5; 95% CI 3.9, 45.9), hypertension (OR 6.4; 95% CI 1.9, 21.9), having ever smoked (OR 2.7; 95% CI 1.1, 6.5), RA duration (OR 1.09; 95% CI 1.06, 1.13) and erosions (OR 2.9; 95% CI 1.1, 8.2)., Conclusions: CV events are prevalent in RA. They are associated with CV risks and RA factors. Despite this burden we found CV risk factors were inadequately managed. A robust system to identify and treat CV risks in RA is required.