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Vasculitis assessments—what do patients think?Paul A. Bacon and Tessa Sanderson

Takayasu arteritis is an understudied disease but a recent article emphasizes the heavy burden it imposes on patients. New assessments devised to improve disease understanding are based on physicians’ concepts of disease severity. However, wide differences exist between patient and physician priorities and more work is now needed to improve patient quality-of-life.Bacon, P. A. & Sanderson, T. Nat. Rev. Rheumatol. advance online publication 8 October 2013; doi:10.1038/nrrheum.2013.150

Major advances in therapeutic options and understanding of disease mechanisms that have occurred in small-vessel vasculitis (SVV) have not yet extended to large-vessel vasculitis (LVV). Takayasu arteritis in par-ticular, which is rare outside the Eastern world, remains the orphan of systemic vasculitides. Indeed, we remain ignorant of many aspects of Takayasu ar teritis, a condition that—as a study of q uality-of-life (QoL) impairment now reminds us1—imposes a heavy burden on patients. The aetiopathology of Takayasu arteritis is poorly understood and the evidence-base for selecting therapy is lamentably slim. Glucocorticoids remain the first-line choice, despite the high relapse rate, and a recommendation from EULAR to consider adding immunosuppressive agents lacks evidence.2 In these circumstances, is our failure to reach a patient-acceptable state of disease control surprising? Substantial case series of patients with Takayasu arteritis are now being amassed by national groups in Turkey, India, and China, as well as in Western Europe. Coupled with the develop-ment of validated disease-assessment tools that can standardize data collection across such series, the time is now ripe to advance our understanding of this disease and seek ways to materially improve patient QoL.

Earlier this year, initial validation of the first tool for assessing clinical disease activ-ity in patients with Takayasu arteritis was published.3 The existing Disease Extent Index was used to capture the clinical profile of Takayasu arteritis in a range of

Indian patients and the data were analysed to develop a specific index of clinical disease activity that can be used to monitor response to therapy.3 Currently, treatment decisions in Takayasu arteritis also take account of acute-phase response and vascular imaging data. Angiography, the gold standard of imaging, provides information on the lumen only (Figure 1). Vessel-wall involvement is detected using MRI for wall thickening or as linear streaks, indicating inflamma-tion, on PET scans. Neither sign, however, relates closely to the clinical disease state of Takayasu arteritis, and both features require further research to elucidate the underlying mechanisms. An alternative and cheaper way to image vessels (at least more super-ficial vessels) is ultra sonography, which is widely used in the temporal ar teritis form of LVV. A paper describing a new standard-ized colour Doppler ultrasonography score of 19 vessels that are commonly involved in Takayasu arteritis has been accepted for publication.4 This new index has real poten-tial as another way to quantitate patient responses to therapy, alongside the clinical activity score.3 Notably missing from these developments are patient-reported outcome measures (PROMs).

Physicians tend to picture Takayasu ar teritis as vessel blockage that results in

ischaemia. Patients, however, view Takayasu arteritis through the lens of a chronic dis-ease that interferes with general health and lifestyle, and that includes the financial burden imposed by long-term medication and costly interventions. In developing countries in particular, an impaired ability to do housework, and fears of infertility, seriously affect the lives of young women —the most frequent demographic of patients with Takayasu arteritis. OMERACT (Outcome Measures in Rheumatology) has stressed the need to include QoL measures in vasculitis assessments.5 Generic QoL indices, such as the 36-item Short Form Health Survey (SF-36®), show that patients with SVV perceive marked reductions in QoL, which correlate poorly with vasculitis-associated damage and persist after appar-ently successful therapy.6 Thus, although the new Turkish report1 is the first to document impaired QoL and mental status in a large-scale study in patients with Takayasu arteri-tis, the overall conclusion is not surprising. The priority now is to pinpoint the cause of this impairment, to facilitate alleviation of the symptoms.

Active disease is the obvious first thought, but only a quarter of patients in the study by Yilmaz et al. had active disease as scored by the Kerr criteria.1 The 43% of patients with disease rated active by physician global assessment might represent the influence of

Figure 1 | Arch aortogram in a patient with Takayasu arteritis. The image shows multiple stenotic lesions and reduced blood flow in major arteries supplying the head typical of Takaysu arteritis. Courtesy of P. A. Bacon.

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patients’ accounts on physicians. Indeed, no correlation between disease activity and patient-reported QoL has been found in previous studies in Takayasu arteri tis. In the study by Yilmaz et al.,1 anxiety and depression were found in patients with both active and inactive disease. Functional disability scores related to all SF-36 sub-group parameters, and no specific disease symptom was associated with impaired function or QoL. Factors unrelated to disease, such as age, had an effect on QoL, but financial burden (which is important in the QoL of patients with SVV) was not studied. The authors make the positive sug-gestion that disease-specific instruments could be developed from patient focus groups and used to clarify the real-world impact of their findings.1 Another option would be to use an instrument such as the Measure Yourself Medical Outcome Profile (MYMOP),7 which could be used to clarify which factors are most important from the patient perspective.

The basic problem in improving QoL for patients seems to be that systemic vasculi-tis, both large and small vessel syndromes, is controlled rather than cured with current treatment, despite advances in therapy over the past decade. Patients, therefore, face the burden of chronic disease (and therapy thereof) together with the fear of relapse. Ideally, disease assessments should encom-pass the views of patients, as is standard research practice for patients with rheuma-toid arthritis (RA). Such PROMs have hardly been approached in vasculitis, although an important study in granulo matosis with polyangiitis showed that patients’ views of disease impact differed widely from phy-sicians’ assessments.8 For example, 95% of patients rated both fatigue and energy loss as more severe than organ manifestations such as renal failure. The lowered physical function noted by Yilmaz et al.1 suggests that similar opinions might be found in patients with Takayasu arteritis. A compar-ison of physician and patient views of the most severe features, such as that by Herlyn

and colleagues,8 should certainly be under-taken in Takayasu arteritis, but, as its clini-cal features differ widely from those of SVV, quite different clinical manifestations might receive high ratings. Thus, disease-specific PROMs for LVV such as Takayasu arteri-tis might now be required, just as specific clinic al disease activity indices were needed.

Although the use of PROMs has become standard in medical research, many ques-tions remain in the development and se lection of these measures, such as how best to incorporate the priorities of patients. Patients are usually involved in the process in many ways, contributing their perspec-tive through qualitative methods, including consensus techniques designed to select core domains to include in PROMs. Patients are also involved in steering committees to support the analysis of new clinical tools, but the most effective way of embedding patient priorities directly into such instruments has yet to be decided. Ought we use tools, such as MYMOP, in which individual patients write their own priorities, or take an Impact Triad approach (severity, importance and self-management) in which set outcomes are rated by patients for importance? 9

Time and context are also important considerations. In chronic progressive conditions, such as Takayasu arteritis, the priorities of patients will change over time. Should self-management and adaptation to the disabling condition also be measured? More over, given that the majority of core sets are currently developed in Western countries, how do we ensure that PROMs are culturally valid in diseases, such as Takayasu arteritis, that are more common in Eastern countries? It might not be suf-ficient to rely on translations of Western-validated instruments. Guidance on the development and selection of domains for PROMs is available from the Core Outcome Measures Effectiveness Trials (COMET) initiative10 and is forthcoming in the new OMERACT ‘Filter 2.0’. This guidance is continually updated, and anyone building on the work by Yilmaz et al.1 will need to implement the best current methodology.

What is clear is that although standardized assessments are essential tools to aid physi-cians’ decisions, they cannot be followed blindly. Old-fashioned d octoring—l istening to patients—enhances science-based medi-cal decisions. Our focus-group work on

patient views of choice in the UK National Health Service demonstrated patients’ strong desire to be listened to, including in the choice of therapy. Clinical practice has established the concept of an ‘accept-able level of disease’ that patients with RA will tolerate to minimize treatment-related problems. We can no longer increase therapy to suppress severe disease, as perceived by physicians, without taking the priorities of patients more seriously.

Department of Rheumatology, The University of Birmingham, Birmingham B15 2TT, UK (P. A. Bacon). Academic Rheumatology, Bristol Royal Infirmary, Bristol BS2 8HW, UK (T. Sanderson). Correspondence to: P. A. Bacon p.a.bacon@bham.ac.uk

AcknowledgementsThe authors would like to thank S. Hewlett for comments on the manuscript.

Competing interestsThe authors declare no competing interests.

1. Yilmaz, N. et al. Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatology (Oxford) http:// dx.doi.org/10.1093/rheumatology/ket238.

2. Mukhtya, C. et al. EULAR recommendations for the management of large vessel vasculitis. Ann. Rheum. Dis. 68, 318–323 (2009).

3. Misra, R. N. et al. Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatology (Oxford) http://dx.doi.org/10.1093/rheumatology/ket128.

4. Sinha, D., Mondal, S., Nag, A. & Ghosh, A. Development of colour Doppler ultrasound scoring system in patients of Takayasu’s arteritis and its correlation with clinical activity score (ITAS 2010). Rheumatology (Oxford) http://dx.doi.org/10.1093/rheumatology/ket289.

5. Merkel, P. A. et al. The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis. J. Rheumatol. 38, 1480–1486 (2011).

6. Walsh, M et al. Health related quality of life in patients with newly diagnosed anti-neutrophil cytoplasm antibody associated vasculitis. Arthritis Care Res. 63, 1055–1061 (2011).

7. Paterson, C. Measuring outcome in primary care: a patient-generated measure, MYMOP, compared to the SF-36 health survey. BMJ 312, 1016–1020 (1996).

8. Herlyn, K. et al. Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective. Arthritis Care Res. 62, 1639–1645 (2010).

9. Sanderson, T. et al. The impact triad (severity, importance and self-management) as a method of enhancing the measurement of the personal life impact of rheumatic diseases (Editorial). J. Rheumatol. 38, 191–194 (2011).

10. Williamson, P. R. et al. Developing core outcome sets for clinical trials: issues to consider. Trials 13, 132–140 (2012).

‘‘Patients … view Takayasu arteritis through the lens of a chronic disease that interferes with general health and lifestyle...’’

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