Reporting Disease Activity in Clinical Trials of Patients With Rheumatoid Arthritis: EULAR/ACR Collaborative Recommendations

Medical University of Vienna, Vienna, Austria.
Arthritis & Rheumatology (Impact Factor: 7.76). 10/2008; 59(10):1371-7. DOI: 10.1002/art.24123
Source: PubMed


To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007).
Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue.
These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

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    • "Rheumatoid arthritis patients generally report higher levels of severe fatigue that can exacerbate other symptoms of the disease, worsen physical and emotional well-being and interfere with employment, social and family opportunities and obligations [20,21]. Fatigue is a common and debilitating symptom in RA patients and both the American College of Rheumatology and European League Against Rheumatism have highlighted the need for more information on fatigue from clinical trials, using validated fatigue scales [22]. Both arms in this study reported a lessening of fatigue symptoms as measured using the FACIT-Fatigue instrument, however, the ETN + MTX arm showed a significantly larger reduction of fatigue symptoms after 16 weeks (8 points or 28% improvement) compared to the DMARD + MTX arm (3 points or 10.4% improvement). "
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    ABSTRACT: Patient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied. Patients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used. Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores. Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region. Trial registration # NCT00422227
    BMC Musculoskeletal Disorders 01/2013; 14(1):13. DOI:10.1186/1471-2474-14-13 · 1.72 Impact Factor
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    • "There are few references to how modern imaging techniques could or should be used to determine if a patient is in remission in these recommendations. However, the EULAR/ACR collaborative recommendations on how to report disease activity in clinical trials include an extensive research agenda highlighting the potential role of imaging modalities in the definition of remission and the role of MRI and ultrasound in measuring synovitis [93]. "
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    ABSTRACT: With recent improvements in the treatment of rheumatoid arthritis (RA), remission has become an achievable goal for a large proportion of RA patients, and remission is now a defined target in current RA guidelines. However, studies have shown that progression of radiographic joint damage may occur in clinical remission, regardless of the choice of remission definition. Sub-clinical inflammation detected by modern imaging techniques such as ultrasonography and magnetic resonance imaging is present in the majority of patients in clinical remission, and is associated with progressive joint damage and disease activity flare in these patients. This chapter aims to assess the importance of imaging findings in RA patients in clinical remission and to discuss the possible role of modern imaging in future remission criteria.
    Best practice & research. Clinical rheumatology 12/2012; 26(6):767-85. DOI:10.1016/j.berh.2012.10.004 · 2.60 Impact Factor
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    • "The various scores that are explored in this study have been evaluated in longitudinal studies and are found to detect improvement during biological medication. So far, most evaluations of response to treatment have been performed by use of the patient's evaluations, clinical examinations and laboratory assessments, and with presentation of composite scores that reflect inflammatory activity [12,26-28], in accordance with the published EULAR/ACR recommendations [29]. US has in previous studies been found to be a valid and reliable examination for assessment of synovitis as well as the degree of vascularization (by use of PD activity) [2-5]. "
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    ABSTRACT: The primary objectives were to explore the associations between a comprehensive ultrasonographic (US) assessment of joints, tendons and bursae and previously described reduced joint counts (7-, 12-, 28- and 44-joint score) as well as to assess the sensitivity to change of these different US joint combinations during biological treatment. Twenty patients with rheumatoid arthritis (RA) were examined by US (B-mode (BM) and power Doppler (PD)) with use of a semi-quantitative (0 to 3) score of 78 joints, 36 tendons/tendon groups and two bursae (hereafter described as the 78-joint score) at baseline and 1, 3, 6 and 12 months after initiating treatment with adalimumab. BM and PD scores for the different joint combinations were generated. The reduced joint scores had high correlation coefficients with the 78-joint score at all examinations (range 0.79 to 0.99 for BM and 0.77 to 0.99 for PD, each P < 0.001) and sum BM and PD scores of all the different joint combinations improved significantly during follow-up (P ≤ 0.05 to 0.001). The reduced joint combinations were highly associated to the 78-joint score. Furthermore, all the joint combinations presently explored responded well to biological treatment. This indicates that an approach focusing on few joints and tendons gives equivalent information about the inflammatory activity in RA patients as a comprehensive US examination. The optimal combination of joints and tendons for a valid, reliable and feasible US measurement should be further explored to define a US score for follow-up of RA patients on biological treatment.
    Arthritis research & therapy 05/2011; 13(3):R78. DOI:10.1186/ar3341 · 3.75 Impact Factor
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