Development of outcome measures for giant cell arteritis for use in clinical trials and standard practice.

BACKGROUND: Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Giant cell arteritis (GCA) is a multifaceted disorder and, therefore, measurement of multiple outcomes is relevant to this illness. It is a privilege to analyze and monitor/transfer long-term patients' management outcomes particularly if the same outcomes are used in practice and in trials. OBJECTIVE: To classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy. METHODS: This study was composed of two steps, instrument design (item generation) and judgmental evidence. A panel of 13 experts was used to validate the instrument through quantitative (content validity) and qualitative (cognitive interviewing) methods. Content validity index was used to assess content validity quantitatively. RESULTS: Five items achieved high content validity where item-content validity index score was >0.79, and in the meantime achieved high content validity response score reflecting greater agreement among panel members. Through qualitative methods, items were improved until saturation was achieved. This agreed with the expert panel ranking of the items included in GCA disease outcome measures set. CONCLUSION: For daily clinical practice, outcome measures should reflect the patients' disease activity status and have to be easily assessed and recorded. The study identified composite outcome measures for GCA able to assess the disease state and monitor response to therapy. Key Points • Despite the cohort studies published in giant cell arteritis (GCA), there are no fully validated outcome measures for use in standard practice or clinical trials. • There is a gap in international standards for assessing GCA disease activity. • Identifying disease specific outcome measures is vital for monitoring response to therapy, treatment case series and therapeutic clinical trials in GCA. • This study was carried out aiming to classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy.

Patient perceptions of health-related quality of life in giant cell arteritis: international development of a disease-specific patient-reported outcome measure.

OBJECTIVES: GCA is a large vessel vasculitis (LVV) presenting with headache, jaw claudication, musculoskeletal and visual involvement. Current treatment is glucocorticoids and anti-IL-6 tocilizumab in refractory disease. The objective of this study was to explore the impact of GCA and its treatment on people's health-related quality of life (HRQoL), to inform the development of a disease-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Participants from the UK and Australia, with biopsy- or imaging-confirmed GCA, were interviewed to identify salient aspects of HRQoL in relation to GCA and its treatment. Purposive sampling included a range of demographic and disease features (cranial, LVV-GCA and visual involvement). Inductive analysis identified individual themes of importance, then domains. Candidate questionnaire items were developed from the individual themes, refined by piloting, cognitive interviews and a linguistic translatability assessment. RESULTS: Thirty-six interviews were conducted to saturation with participants with GCA from the UK (25) and Australia (11). Mean age was 74 years, 23 (63.9%) were female, 13 (36.1%) had visual loss and 5 (13.9%) had LVV-GCA. Thirty-nine individual themes within five domains were identified: physical symptoms; activity of daily living and function; participation; psychological impact; and impact on sense of self and perception of health. Sixty-nine candidate items were developed from individual themes; piloting and refinement resulted in a 40-item draft questionnaire. CONCLUSION: This international qualitative study underpins the development of candidate items for a disease-specific PROM for GCA. The draft questionnaire is now ready for psychometric testing.

The prevalence and impact of depression in primary systemic vasculitis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of depression among patients with primary systemic vasculitides (PSV); compare prevalence according to vasculitis type and against controls; and examine the impact of depression on PSV outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with PRISMA guidelines. We included all studies that reported the prevalence or impact of depression in PSV. We also included polymyalgia rheumatica (PMR) given its association with giant cell arteritis (GCA). Meta-analyses of prevalence estimates were performed using random-effects models and reported as percentages (95% confidence interval). RESULTS: We reviewed a total of 15 studies that described the prevalence of depression, categorised into small (n = 10) and large vessel vasculitis (n = 7). Pooled prevalence estimate for depression in a small vessel (predominantly ANCA-associated) vasculitis was 28% (95% CI 20-38%) with significant heterogeneity (I2 = 93%). Depression prevalence in large-vessel vasculitis (Takayasu and GCA/PMR) was 24% (95% CI 17-34%), again with significant heterogeneity (I2 = 96%). One study reported 56% prevalence of depression in medium vessel disease. The prevalence of depression in small vessel vasculitis was higher than healthy controls. In these patients, depression and depressive symptoms were associated with poorer quality of life, adherence, and work disability, but not disease activity or damage. CONCLUSION: Depression is highly prevalent among patients with primary systemic vasculitis and associated with poorer outcomes across a range of measures in studies of small vessel disease. Further studies are needed for depression in medium and large vessel vasculitides.

Cognitive deficits in vasculitis of the nervous system: a cross-sectional study.

Objectives: To identify the cognitive and functional deficits in a well-characterized group of patients with vasculitis of the nervous system. Methods: Sixty-seven patients diagnosed with Central Nervous System (CNS) or Peripheral nervous System (PNS) vasculitis over a 14-year period were retrospectively identified. Data on clinical presentation, laboratory, radiographic and tissue biopsy investigations, and treatment were collated. Cognitive, functional and quality of life evaluation assessments were performed in 31 patients who agreed to participate and included Addenbrooke's Cognitive Examination-revised (ACE-R), Nottingham Extended Activities of Daily Living (NEADL) and EQ-5D-3L quality of life questionnaires. Results: CNS vasculitis patients exhibited cognitive impairment, with a mean ACE-R score of 74/100 (standard deviation (SD) 16). NEADL and EQ-5D-3L scores were in the impaired range at 41/66 (SD 21) and 57/81 (SD 22), respectively. Patients with just PNS vasculitis exhibited fewer cognitive deficits with ACE-R and NEADL scores of 87 (SD 8) and 46 (SD 16) respectively. EQ-5D-3L score was in the impaired range of 65 (SD 22). Conclusions: Vasculitis of the nervous system and, in particular, CNS vasculitis causes cognitive impairment and deficits in functional ability. Such patients should be targeted for cognitive rehabilitation.

Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial.

BACKGROUND: Patients with giant cell arteritis (GCA) treated with tocilizumab (TCZ) every week or every other week and prednisone tapering achieved superior rates of sustained remission to patients treated with placebo and prednisone tapering in a randomised controlled trial. Health-related quality of life (HRQOL) in patients from this trial is now reported. METHODS: Exploratory analyses of SF-36 PCS and MCS and domain scores, PtGA and FACIT-Fatigue were performed in patients treated with weekly subcutaneous TCZ 162 mg plus 26-week prednisone taper (TCZ-QW + Pred-26) or placebo plus 26-week or 52-week prednisone tapers (PBO + Pred-26 or PBO + Pred-52). These analyses were performed on responder and non-responder patients, including those who achieved the primary outcome and those who experienced flare and received escape prednisone doses. RESULTS: Baseline SF-36 PCS, MCS and domain scores were low, indicating impaired HRQOL related to GCA. At week 52, least squares mean (LSM) changes in PCS scores improved with TCZ-QW + Pred-26 but worsened in both PBO + Pred groups (p <  0.001). LSM changes in MCS scores increased with TCZ-QW + Pred-26 versus PBO + Pred-52 (p < 0.001). Treatment with TCZ-QW + Pred-26 resulted in significantly greater improvement in four of eight SF-36 domains compared with PBO + Pred-26 and six of eight domains compared with PBO + Pred-52 (p < 0.01). Improvement with TCZ-QW + Pred-26 met or exceeded minimum clinically important differences (MCID) in all eight domains compared with five domains with PBO + Pred-26 and none with PBO + Pred-52. Domain scores in the TCZ-QW + Pred-26 group at week 52 met or exceeded age- and gender-matched normative values (A/G norms). LSM changes from baseline in FACIT-Fatigue scores increased significantly with TCZ-QW + Pred-26, exceeding MCID and A/G norms (p < 0.001). CONCLUSIONS: Patients with GCA receiving TCZ-QW + Pred-26 reported statistically significant and clinically meaningful improvement in SF-36 and FACIT-Fatigue scores compared with those receiving prednisone only. Improvements in the TCZ-QW + Pred-26 group led to recovery of HRQOL to levels at least comparable to those of A/G-matched normative values at week 52 and exceeded normative values in five of eight domains. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01791153. Date of registration: February 13, 2013.

Support available for and perceived priorities of people with polymyalgia rheumatica and giant cell arteritis: results of the PMRGCAuk members' survey 2017.

Polymyalgia rheumatica and giant cell arteritis are relatively common, but under research inflammatory rheumatological conditions. This survey aimed to ascertain the matters in which patients feel they need support with these conditions and appraise how the Charity PMRGCAuk currently supports these needs and could do so in the future. PMRGCAuk members (n = 910) were invited to complete an on-line survey. The survey requested the respondent's history of PMR and or GCA, their perceived priorities for support for people with PMR and or GCA and views on the services already provided by the Charity. A total of 209 people completed the survey. Less than 24% had heard of either PMR or GCA before their diagnosis. Priorities in supporting people with PMR and or GCA included: being on and tapering off glucocorticoids (76.6%), specifically, length of treatment and the risks versus benefits and managing side effects. Respondents generally reported satisfaction with the services currently provided by PMRGCAuk. The support provided by PMRGCAuk is very helpful to members and fills an important gap in provision for people with PMR and or GCA. The areas in which the greatest proportions of participants requested support do not have an evidence base to underpin them. It is incumbent on the research community to address patients' concerns and provide an evidence base where it is required by those affected.

Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016.

OBJECTIVE: Among the challenges in conducting clinical trials in large-vessel vasculitis (LVV), including both giant cell arteritis (GCA) and Takayasu arteritis (TA), is the lack of standardized and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group initiated an international effort to develop and validate data-driven outcome tools for clinical investigation in LVV. METHODS: An international Delphi exercise was completed to gather opinions from clinical experts on LVV-related domains considered important to measure in trials. Patient interviews and focus groups were completed to identify outcomes of importance to patients. The results of these activities were presented and discussed in a "Virtual Special Interest Group" using telephone- and Internet-based conferences, discussions through electronic mail, and an in-person session at the 2016 OMERACT meeting. A preliminary core set of domains common for all forms of LVV with disease-specific elements was proposed. RESULTS: The majority of experts agree with using common outcome measures for GCA and TA, with the option of supplementation with disease-specific items. Following interviews and focus groups, pain, fatigue, and emotional effect emerged as health-related quality of life domains important to patients. Current disease assessment tools, including the Birmingham Vasculitis Activity Score, were found to be inadequate to assess disease activity in GCA and standardized assessment of imaging tests were felt crucial to study LVV, especially TA. CONCLUSION: Initial data from a clinician Delphi exercise and structured patient interviews have provided themes toward an OMERACT-endorsed core set of domains and outcome measures.

What is the impact of giant cell arteritis on patients' lives? A UK qualitative study.

OBJECTIVES: Clinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients' lives. METHODS: UK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed. RESULTS: 24 participants were recruited (age: 65-92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and 'life-changing' impacts. The overall impact of GCA on patients' lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision. CONCLUSIONS: The impact of GCA in patients' everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients' experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives.

[Effect of stressful life events on clinical development of temporal arteritis and/or polymyalgia rheumatica]. / Influence des événements stressants de la vie sur l'émergence clinique de l'artérite temporale et/ou de la pseudopolyarthrite rhizomélique.

OBJECTIVES: To test the hypothesis of an epidemiological relationship between stressful events and the date of emergence of temporal arteritis and/or polymyalgia rheumatica. METHODS: Thirteen patients identified with anatomo-clinical criteria and whose mental state permitted prolonged questioning where included in the survey. A list of 65 events, covering the 2-year period preceding the onset of temporal arteritis and/or polymyalgia rheumatica, was used. Each event was assessed using an emotional scale with positive (1 to 10) or negative scores (-1 to -10). Zero corresponded to an event without impact. An event score was drawn-up for each patient. The results were compared with those of a control group of 26 paired (age and gender) controls, 2 controls for each patient were included. RESULTS: In the group of patients, 12/13 (92.3%) had suffered from negative events 2 years before diagnosis of their disease, with a total of 35 negative events and a score of -271. In the control group, only 10/26 (38.8%) had suffered from negative events with a total of 21 negative events and a score of -132. The comparison (chi 2 test) of the total of recent negative events (2 years before diagnosis) for both groups, i.e., 35/112 versus 21/232, revealed a highly significant difference (chi 2 = 27.3; p < 0.00001). Conversely, there was no significant difference between the two groups regarding the total events having occurred throughout their lifetime. CONCLUSION: This result suggests the influence of stressful events in the clinical emergence of temporal arteritis and/or polymyalgia rheumatica.

Visual function and quality of life among patients with giant cell (temporal) arteritis.

OBJECTIVE: To investigate patient perception of visual and systemic disability associated with giant cell arteritis (GCA) and whether the perceived disability can be correlated with visual performance measures. METHODS: We prospectively evaluated and compared the visual performance and quality of life survey for 20 patients with GCA after 4 to 5 weeks of corticosteroid therapy and after one year of therapy. We measured visual acuity, contrast sensitivity, and threshold perimetry and patients completed the Activities of Daily Vision Scale (ADVS) and the short-form of the Health Survey (SF-36). The results were grouped by GCA affected or unaffected eye or by better or worse eye and reported as a decimal and percent impairment for acuity, log units for contrast, mean deviation and the Advanced Glaucoma Intervention Study (AGIS) score for perimetry. The results for patients with and without visual loss were compared. Correlation analyses between ADVS categories and visual performance measures, SF-36 categories and the presence of visual loss, total corticosteroid dose, systemic symptoms, secondary hypertension or diabetes mellitus, the presence of vertebral fracture, and visual performance were performed. RESULTS: Day driving was the only ADVS category significantly reduced at baseline in patients with visual loss (62.5) compared with those without visual loss (96.3, P = 0.04). Modest to moderate correlations between ADVS categories were most frequent for percent binocular acuity impairment with day driving (r = -0.62, P = 0.017), with distance vision (r = -0.5, P = 0.02), and with glare (r = -0.59, P = 0.006); and the AGIS score of the worse eye with day driving (r = -0.66, P = 0.01), with near vision (r = -0.49, P = 0.03), and with glare (r = -0.48, P = 0.04). The baseline SF-36 scores did not correlate with the presence of vision loss at baseline or systemic complications. The ADVS and SF-36 scores were similar at one year. The total dose of corticosteroids only had a modest correlation with the one-year mental health score (r = -0.45, P = 0.05), but there was no correlation between SF-36 scores and other systemic side effects of steroid therapy. CONCLUSION: Except for the day driving score, the ADVS did not differ between patients with and without visual loss. The SF-36 did not distinguish between patients with and without visual loss and did not reveal significant trends. The ADVS and SF-36 did not reveal significant disability in GCA patients and there were no strong correlations with any visual performance or systemic measures.

Giant cell (temporal) arteritis-polymyalgia rheumatica: a critical review.

Giant cell (temporal) arteritis G.C.(T) A. is common disorder and affects medium sized and large arteries in people over the age of fifty. Many series show that up to 50% of people with the clinical syndrome of polymyalgia rheumatica (PMR) go on to develop manifestations of G.C.(T) A. within a year; others may do so later. A critical review is offered of aspects of the subject which despite much study and research remain controversial or neglected. This includes epidemiology: statistics from routine autopsy suggests that the disease affects more people than are diagnosed clinically. The need to resolve uncertainty whether intracerebral vessels are involved or not, is now urgent, particularly in view of the wide spread use of short courses of Dexamethasone in the treatment of stroke. All clinicians should recognise the implications of the fact that they are dealing with a disease which may be active and yet symptomatically silent.

Mental status abnormalities in temporal arteritis: a treatable cause of dementia in the elderly.

Although temporal arteritis (TA) is a common vasculitis, mental status changes and higher cortical dysfunction have received limited attention in the literature. We report a case which illustrates the potential for TA to produce chronic fluctuating delirium, delusional thinking, and memory impairment in the absence of concomitant symptoms of headache and visual loss. In addition, TA may produce differing symptoms at different times in the same patient.

Pathological mourning: a key factor in the psychopathogenesis of autoimmune disorders. A special contribution.

Prolonged mourning has been recorded as a precipitant life event in RA and other autoimmune disorders, but other events such as retirement, redundancy and injury have also been identified. The author's submission is that pathological mourning is present in all patients with AI disease, and that other events such as those mentioned are only precipitant because they uncover mourning until then kept in check by occupation and use of work as a drug. When time for reflection and loneliness allows long suppressed ambivalent feelings, guilt and bitterness to surface, remorse over 'unfinished business' increasingly dominates the patient's thoughts. Children and young people rarely have the opportunity to mourn, thus early loss is often paramount and is awakened from the unconscious years later when further losses of key figures or surrogates, including pets, occur or are anticipated. Psychotherapy involves helping patients resolve their pathological mourning.

Coronary ischaemia and occlusion in giant cell (temporal) arteritis.

Reports of coronary artery involvement in giant cell (temporal) arteritis--polymyalgia rheumatica (GC(T)A--PMR) together with other large arteries arising from the aorta have been numerous over the past 40 years, but on this the specialist cardiac literature has been virtually silent. This article summarises that evidence, and records nine additional patients from a large group of cases with both GC(T)A--PMR and ischaemic heart disease (IHD) observed since a previous report in 1960. The case histories illustrate the benefit from corticosteroids and the hazards of non-diagnosis and premature cessation of such treatment. It seems that many patients with arteritic IHD (and claudication) are not being identified before or after death. Possible reasons for this oversight by clinicians and pathologists are offered, and suggestions are made with regard to points in history-taking and important physical signs which may help to alert the clinician. There is autopsy evidence from Malmö, Sweden, that the prevalence of GC(T)A--PMR is much higher than at present suspected on clinical grounds.

Reversible mental symptoms in temporal arteritis.

Mental symptoms are common in temporal arteritis. Reported here is a case in which a deficit in nonverbal memory documented with psychological testing resolved after a course of steroids. Besides the global confusional states commonly seen in temporal arteritis, focal intellectual impairment may be seen. It seems possible that some patients presenting with dementia as well as focal mental signs may have temporal arteritis. The diagnosis can easily be made by performing an erythrocyte sedimentation rate and temporal artery biopsy.