Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly ...after rheumatoid arthritis. Glucocorticoids are the cornerstone of treatment for GCA and PMR, which are interrelated diseases. Glucocorticoids are effective, but adverse effects occur in a high proportion of patients. Careful use of glucocorticoids and the application of preventive strategies can minimize these adverse effects. Possible long-term complications of GCA include aneurysm and stenosis of vessels, even in patients with apparently clinically inactive disease; acute blindness is rare during glucocorticoid treatment. In PMR, whether subclinical chronic inflammation can lead to long-term damage is less clear. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states, such as low disease activity or vessel damage without active disease. In this Review, we outline current evidence on the monitoring and long-term management of patients with GCA and PMR, including the tapering of treatment.
To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
A systematic literature review was conducted to retrieve data on treatment targets and ...outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously.
Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment.
These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.
•More than a quarter of patients with PMR may have subclinical GCA at diagnosis.•Meta-analysis of a large patients’ data set could not identify a marker for subclinical GCA.•Classical inflammatory ...parameters such as ESR and CRP were not associated with subclinical GCA.•A paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed.
To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR).
PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT).
We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I2=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I2=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75).
More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed.
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To summarise evidence on therapeutic interventions and prognostic factors in polymyalgia rheumatica (PMR). A systematic literature review was conducted using Ovid Medline, Embase, PubMed, CINAHL, Web ...of Science and the Cochrane Library (1970 through April 2014). Quality of evidence (QoE) of identified studies was appraised by Grading of Recommendations Assessment, Development and Evaluation (GRADE) (interventions) and the Quality In Prognosis Studies (QUIPS) methodologies (prognostic factors). Out of 10 931 titles identified, 52 articles were finally selected. A single study indicated that an initial prednisone dose of 20 mg/day is associated with a lower short-term relapse rate than 10 mg/day but at the cost of a higher rate of adverse events. Another study suggested a comparable efficacy of intramuscular methylprednisolone and oral glucocorticoids (GCs) with lower cumulative GC doses and less weight gain in the former group. Moderate to high QoE (1-2 studies) indicated a benefit of methotrexate in remission rates and cumulative GC doses in early PMR. Anti-tumour necrosis factor α agents are ineffective for PMR treatment. Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk. Women and patients with high ESR also appeared to have a longer duration of treatment. Several studies of varying quality, however, failed to prove these associations. In PMR, evidence for initial GC doses and subsequent tapering regimens is limited. Intramuscular methylprednisolone and methotrexate may be effective GC sparing agents. Female sex, high ESR and peripheral arthritis at disease outset are potential risk factors for a worse prognosis.
Peripheral arthritis has been described in up to 50% of PMR patients, with knee involvement in the majority. This study was designed to evaluate by PET/CT the knees of patients with PMR and GCA and ...to identify the knee structures involved by inflammation.
Twenty-five consecutive patients with PMR (19) or GCA (6) were studied in comparison with 25 age- and sex-matched controls who underwent PET/CT for initial staging of cancer. Clinical features, ESR and CRP were evaluated. Simultaneous FDG-PET and CT imaging from the skull base to the knee was performed after injection of 4.8-5.2 MBq of (18)FFDG per kilogram body weight. The knee anatomical structures being evaluated included joints, fibrous capsule, synovial recesses and bursae.
At PET/CT, 21/25 patients (84%) showed bilateral diffuse uptake at the knees. The tracer clearly outlined the contour of the fibrous capsule. In 50 knees, 90% of capsular sites were involved by inflammation in comparison with 23% of intracapsular sites and 4.7% of extracapsular sites (P < 0.0001). No correlation was found between PET/CT results and ESR or CRP. FDG uptake, with a pattern similar to that observed in 96% of PMR/GCA patients, was seen in 20% of controls (P = 0.03).
Our findings suggest that bilateral capsulitis of the knee is detectable in most PMR/GCA patients if a sensitive imaging technique such as PET/CT is used.
To identify criteria and descriptors used to measure response to treatment and change in disease activity in giant cell arteritis (GCA).
A systematic literature review (SLR) to retrieve randomised ...controlled trials (RCTs) and longitudinal observational studies (LOS). Criteria and descriptors of active disease, remission, response, improvement, worsening and relapse were extracted. RCTs, LOS with >20 subjects, and qualitative research studies were included.
10 593 studies were retrieved, of which 116 were included (11 RCTs, 104 LOS, 1 qualitative study). No unified definition of response to therapy was found. Most RCTs used composite endpoints to assess treatment outcomes. Active disease was described in all RCTs and 19% of LOS; and was largely defined by a combination of clinical and laboratory components. Remission was reported in 73% of RCTs and 42% of LOS; It was predominantly defined as the combination of clinical and laboratory components. One LOS reported response with a definition resembling the definition of remission from other studies. Improvement was rarely used as an endpoint and it was mostly a surrogate of remission. No study specifically defined worsening. Relapse was reported in all RCTs and 86% of LOS. It was predominantly defined as the combination of clinical, laboratory and treatment components.
The results of this SLR demonstrate that definitions of response used in clinical studies of GCA are scant and heterogeneous. RCTs and LOS mainly used remission and relapse as treatment outcomes. The descriptors identified will inform the development of the future European Alliance of Associations for Rheumatology-American College of Rheumatology response criteria for GCA.
Abstract
PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and ...clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction.
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