Marieke Scholte-Voshaar

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

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.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update

Objective A systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations. Methods Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014. Results Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care. Conclusions The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care.

Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis

Objectives To assess the efficacy and safety of synthetic disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA)—a first step in a European League Against Rheumatism (EULAR) initiative to produce recommendations for the management of RA. Methods A systematic review of the literature using PubMed, Embase and the Cochrane library was performed up to January 2009. All randomised controlled trials (RCTs) reporting the efficacy of synthetic DMARDs (vs placebo or other synthetic DMARDs) on signs and symptoms, disability and/or radiographic structural damage in patients with RA were selected. Studies of biological agents or glucocorticoids were excluded. A pooled effect size (ES) was calculated by meta-analysis. Safety and the occurrence of infections and neoplasia was also assessed. Results 97 RCTs (14 159 patients) were analysed for efficacy. The pooled analysis indicated that methotrexate (MTX) was more efficacious in reducing signs and symptoms, disability and radiographic structural damage than other synthetic DMARDs pooled: ES for swollen joint count (SJC) versus pooled DMARDs=1.42 (95% CI 0.65 to 2.18). Leflunomide appeared to be as effective as MTX. Sulfasalazine and injectable gold were efficacious in reducing signs and symptoms and structural damage. Ciclosporin, minocycline, tacrolimus and hydroxychloroquine showed some efficacy in reducing SJC. Auranofin and D-penicillamine showed no significant superiority over placebo. The risks of cancer and of infection were increased with cyclophosphamide and azathioprine. Conclusions MTX was well-tolerated and effective in reducing signs and symptoms, disability and structural damage. A comparison with other synthetic DMARDs was in favour of MTX, though at the tested doses MTX and leflunomide were equally effective.

Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative

Background: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. Objective: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. Methods: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to “distribute 100 points” among the seven domains. The average ranks of importance of these domains were then computed. Results: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. Conclusion: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

European League Against Rheumatism recommendations for the inclusion of patient representatives in scientific projects

Objective To develop recommendations to enable successful inclusion of the patient perspective in European League Against Rheumatism (EULAR)-funded scientific research projects. Methods The EULAR standardised operational procedures for guideline development were followed. A systematic literature review was presented during a first task force meeting, including 3 rheumatologists, 1 rheumatologist/epidemiologist, 2 allied health professionals, 2 representatives of arthritis research organisations and 7 patient representatives, resulting in 38 statements. A Delphi method was carried out to reduce and refine the statements and agree on a set of eight. Next, a survey among a wider group of experts, professionals and patient representatives (n=42), was completed. Feedback from this wider group was discussed at the second meeting and integrated in the final wording of the recommendations. Subsequently, the level of agreement of the group of experts (n=81) was re-evaluated. Results The project resulted in a definition of patient research partner and agreement on a set of eight recommendations for their involvement in research projects. These recommendations provide practical guidance for organising patient participation, capturing (1) the role of patient research partners, (2) phase of involvement, (3) the recommended number, (4) recruitment, (5) selection, (6) support, (7) training and (8) acknowledgement. Conclusion Collaboration between patients and professionals in research is relatively new. Trials or effectiveness studies are not yet available. Nevertheless, it is possible to define recommendations for the inclusion of patients in research following a solid expert opinion based consensus process.

EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis

Objectives The authors aim to develop European League Against Rheumatism recommendations for the role of the nurse in the management of patients with chronic inflammatory arthritis, to identify a research agenda and to determine an educational agenda. Methods A task force made up of a multidisciplinary expert panel including nurses, rheumatologists, occupational therapist, physiotherapist, psychologist, epidemiologist and patient representatives, representing 14 European countries, carried out the development of the recommendations, following the European League Against Rheumatism standardised operating procedures. The task force met twice. In the first meeting, the aims of the task force were defined, and eight research questions were developed. This was followed by a comprehensive, systematic literature search. In the second meeting, the results from the literature review were presented to the task force that subsequently formulated the recommendations, research agenda and educational agenda. Results In total, 10 recommendations were formulated. Seven recommendations covered the contribution of nurses to care and management: education, satisfaction with care, access to care, disease management, psychosocial support, self-management and efficiency of care. Three recommendations focused on professional support for nurses: availability of guidelines or protocols, access to education and encouragement to undertake extended roles. The strength of the recommendations varied from A to C, dependent on the category of evidence (1A–3), and a high level of agreement was achieved. Additionally, the task force agreed upon 10 topics for future research and an educational agenda. Conclusion 10 recommendations for the role of the nurse in the management of chronic inflammatory arthritis were developed using a combination of evidence-based and expert consensus approach.

Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions

Background Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. Methods Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. Results The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. Conclusions The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.

The patient perspective on remission in rheumatoid arthritis: ‘You've got limits, but you're back to being you again’

OBJECTIVES The aim of rheumatoid arthritis (RA) treatment is remission. As treatment should be targeted at outcomes relevant to patients, it is important to understand how patients perceive remission, and to assess whether the current definition of remission adequately reflects these perceptions. The objective of this study is to explore the patient perspective on remission in RA. METHODS Nine focus-group discussions in Austria, The Netherlands and UK were conducted, including patients in American College of Rheumatology (ACR)/ European League of Rheumatology (EULAR) remission, self-declared remission and in moderate/high disease activity. Moderators employed a prespecified interview guide helped to engage patients in a discussion on their experience with remission. Inductive thematic analysis was performed within each country, and identified themes were discussed across countries. RESULTS 47 RA patients (66% women, disease duration 9 years) participated. Three major themes of patient-perceived remission emerged: (1) symptoms would either be absent or strongly reduced, (2) impact of the disease on daily life would diminish by increased independence, ability to do valued activities, improved mood and ability to cope; (3) leading to a return to normality, including work, family role and perception of others. Patients felt the concept of remission was influenced by ageing, side effects of medication, comorbidities, accrued damage to joints and disease duration. Opinions on duration of state, the role of medication and measurement instruments varied widely. CONCLUSIONS Patients characterise remission by the absence or reduction of symptoms, but more directly by decreased daily impact of their condition and the feeling of a return to normality. The next step is to study whether an additional patient-perceived measure of remission may add value to the ACR/EULAR definition of remission.

The Impact of Coping Strategies on Mental and Physical Well-Being in Patients with Rheumatoid Arthritis

OBJECTIVE To investigate the relation of coping strategies to coping effectiveness, helplessness, and mental as well as physical well-being as indicators of quality of life. METHODS Cross-sectional international study. Coping strategies were assessed by a validated 18-item questionnaire, while coping effectiveness and helplessness were measured by numerical rating scales. The predictability of both and quality of life (SF-36) was evaluated by multiple linear regression including demographic and disease-related factors. RESULTS Four hundred thirty-four rheumatoid arthritis (RA) patients (77% female; mean age 55.96 ± 13.34 years) were included. Distancing was the coping strategy used most frequently in RA patients (mean ± SD 1.89 ± 0.78 on a scale ranging from 0 to 3). Female RA patients used coping strategies significantly more often than males, whereas age and duration of disease did not seem to influence the use of coping strategies. Cognitive reframing and active problem-solving contributed to coping effectiveness while emotional expression was related to helplessness. Coping effectiveness was positively related to general health perception, suggesting certain coping strategies to be effective in influencing the quality of life of RA patients. CONCLUSIONS Coping strategies used in RA are dependent on gender, but not on age. The use of problem-focused coping strategies may allow for an improved coping effectiveness in patients with RA, while also influencing mental and physical well-being as indicators of quality of life. Coping should therefore be considered as an important factor in determining the overall health state of patients with RA.