In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

/pdf/eular-recommendations-for-the-management-of-rheumatoid-4fujp4paik.pdf

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Objective
To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA).

Methods
We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences.

Results
The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional.

Conclusion
This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1002/art.39480

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.23721

American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

https://ard.bmj.com/content/annrheumdis/69/6/964.full.pdf

Background: Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect. Objective: To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years. Design: Double blind placebo controlled trial. Methods: Patients with rheumatoid arthritis, duration Results: 90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years. Conclusions: Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs.

https://ard.bmj.com/content/annrheumdis/63/7/797.full.pdf

Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial

OBJECTIVE—To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years.
METHODS—440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1= 0-2 years n=106, group 2 = >2-5 years n=93, and group 3= >5 years n=235).
RESULTS—There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n=44 (42%), group 2 n=37 (40%), and group 3 n=79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p<0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p<0.05) in each group apart from pain in group 2.
CONCLUSION—Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.

Keywords: gold; rheumatoid arthritis; function; HAQ

https://ard.bmj.com/content/annrheumdis/57/2/88.full.pdf

Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study

Objective—Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the eVect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. Methods—814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. Results—The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to diVerences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. Conclusion—RA patients from deprived areas have poorer function, which is associated with greater need—medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation. (Ann Rheum Dis 1997;56:410‐413) The eVect of socioeconomic disadvantage on mortality patterns is well documented and has important implications for health care strategies. 12 The eVect of deprivation on the course and outcome of a chronic disease such as rheumatoid arthritis (RA) may also be important and may influence patient welfare over many years or indeed decades. Formal education may be regarded as a surrogate marker of socioeconomic status although there are many confounding factors. Pincus et al have shown that outcome of RA in terms of laboratory and functional measurements of disease activity is inversely related to the number of years of formal education in the USA. 3

https://ard.bmj.com/content/annrheumdis/56/7/410.full.pdf

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

Aims: To ascertain if attending a specialist nurse, in addition to routine medical care, would increase the success in dealing with lifestyle variables in a cohort of patients with RA. 

Methods: Twenty two consecutive patients starting treatment with the disease modifying antirheumatic drug (DMARD) sulfasalazine were invited to attend an additional clinic dealing with lifestyle factors every 12 weeks over a 48 week follow up. Smoking and alcohol history, baseline demographic and metrology assessments were determined for all patients. Body mass index (BMI) was calculated, blood pressure recorded, function assessed by the Health Assessment Questionnaire (HAQ), and social deprivation determined by the Carstairs Index. Patients were advised on exercise and diet, and serum cholesterol was measured. 

Results: Twenty women and two men, with a mean age of 52 years and mean disease duration of five years, were enrolled. Eight patients smoked and, unfortunately, none were persuaded to discontinue. Fifteen of the cohort were already taking regular exercise; one additional patient began swimming regularly. At baseline, 10 patients were found to have a high cholesterol, with a mean of 6.8 mmol/l. A 14% reduction in mean cholesterol was achieved by dietary modification, and three patients merited statin treatment. Obesity is a major problem in our population and 15 of the patients had grade I obesity with a mean BMI of 30.6; five of these gained a further 4.5 kg. Six patients with previously untreated hypertension were identified, but unfortunately five remained hypertensive and only two had received anti-hypertensive drugs. 

Conclusions: Educating patients in order to change lifestyle habits and influence outcome is a long term challenge facing all healthcare workers. In our cohort, most adverse lifestyle factors had already been recognised and discussed by the general practitioner or at prior clinic visits. Additional advice and input led to only modest improvement.

https://ard.bmj.com/content/annrheumdis/61/1/66.full.pdf

Can intervention modify adverse lifestyle variables in a rheumatoid population? Results of a pilot study

BACKGROUND—Socioeconomic deprivation is associated with increased mortality from cardiovascular causes and malignancy. The influence of disadvantage in patients with rheumatoid arthritis (RA), who are known to have premature mortality, has not been ascertained.
AIM—To assess the relation between the level of patient deprivation and mortality in RA patients.
METHODS—200 RA patients, enrolled in a study comparing sulfasalazine and penicillamine in 1984-85, have been followed up prospectively for 12 years. Subjects were categorised into Carstairs groups with deprivation scores ranging from 1 (most affluent) to 7 (most deprived). Information about deaths was obtained from the Registrar General in Scotland, death certificates and GP/hospital records.
RESULTS—There were more RA patients in the deprived areas then expected compared with the West of Scotland and England and Wales. Some 47.5% of the RA patients had died by 12 years—the majority of cardiorespiratory causes or malignancy. There were no differences in the median age or disease duration in the various Carstairs groups at study entry, but the percentage of deaths was higher in the more deprived groups after 12 years (36% dead in most affluent area compared with 61% in the most deprived, that is, in groups 6 and 7).
CONCLUSION—In patients with RA increasing deprivation was associated with premature mortality. If confirmed elsewhere these findings have implications for rheumatological management strategies, for researchers involved in collaborative studies of patients from different socioeconomic backgrounds and for resource allocation.

https://ard.bmj.com/content/annrheumdis/58/9/525.full.pdf

E A Thomson

Papers

Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial

Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

Can intervention modify adverse lifestyle variables in a rheumatoid population? Results of a pilot study

Does social disadvantage contribute to the excess mortality in rheumatoid arthritis patients