ABSTRACT
Polymyalgia rheumatica is an inflammatory disease producing pain and stiffness, mainly in the shoulders and pelvic girdle, in people older than 50 years. Elevation of acute phase reactants is common due to the inflammatory nature of the disease. Since there are no specific diagnostic tests, diagnosis requires the exclusion of other diseases with similar presentations. Imaging has helped to identify the pathological substrate of polymyalgia rheumatica and it is increasingly used to support clinical diagnosis or to detect coexistent giant cell arteritis. Although polymyalgia rheumatica does not clearly impair survival or organ function, it can have a detrimental effect on quality of life. Glucocorticoids at 12·5-25·0 mg prednisone per day are effective in inducing remission in most individuals but, when tapered, relapses occur in 40-60% of those affected and side-effects are common. Assessment of disease activity can be difficult because pain related to common comorbidities such as osteoarthritis and tendinopathies, can return when glucocorticoids are reduced, and acute phase reactants are increased less during flares in individuals undergoing treatment or might increase for other reasons. The role of imaging in assessing disease activity is not yet completely defined. In the search for more efficient and safer therapies, tocilizumab and sarilumab have shown efficacy in randomised controlled trials and additional targeted therapies are emerging. However, judicious risk-benefit balance is essential in applying therapeutic innovations to people with polymyalgia rheumatica.
Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/drug therapy , Quality of Life , Diagnosis, Differential , Glucocorticoids/therapeutic use , Pain/drug therapy , Acute-Phase Proteins/therapeutic useABSTRACT
OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Giant Cell Arteritis/complications , Polymyalgia Rheumatica/epidemiology , Quality of Life , ComorbidityABSTRACT
OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.
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OBJECTIVES: To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA. METHODS: A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators. RESULTS: Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each). CONCLUSIONS: This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.
Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Giant Cell Arteritis/drug therapy , Polymyalgia Rheumatica/drug therapy , Glucocorticoids/therapeutic useABSTRACT
OBJECTIVE: To perform a systematic literature review on definitions and instruments used to measure remission, relapse, and disease activity in polymyalgia rheumatica (PMR), to inform an OMERACT project to endorse instruments for these outcomes. METHODS: A search of Pubmed/MEDLINE, EMBASE, CINAHL, Cochrane, and Epistemonikos was performed May 2021 and updated August 2023. Qualitative and quantitative studies published in English were included if they recruited people with isolated PMR regardless of treatment. Study selection and data extraction was performed independently by two investigators and disagreement was resolved through discussion. Data extracted encompassed definitions of disease activity, remission and relapse, and details regarding the instruments used to measure these outcomes. RESULTS: From the 5,718 records, we included 26 articles on disease activity, 36 on remission, and 53 on relapse; 64 studies were observational and 15interventional, and none used qualitative methods. Some heterogeneity was found regarding definitions and instruments encompassing the domains pain, stiffness, fatigue, laboratory markers (mainly acute phase reactants), and patient and physician global assessment of disease activity. However, instruments for clinical signs were often poorly described. Whilst measurement properties of the polymyalgia rheumatica activity score (PMR-AS) have been assessed, data to support its use for measurement of remission and relapse is limited. CONCLUSION: Remission, relapse, and disease activity have been defined heterogeneously in clinical studies. Instruments to measure these disease states still need to be validated. Qualitative research is needed to better understand the concepts of remission and relapse in PMR. REVIEW REGISTRATION: PROSPERO identification: CRD42021255925.
ABSTRACT
Glucocorticoids (GCs) are the gold standard for treatment of giant cell arteritis (GCA); however, there is a need for studies on GC-sparing agents, given that up to 85% of patients receiving GC only develop adverse events. Previous randomised controlled trials (RCTs) have applied different primary endpoints, limiting the comparison of treatment effects in meta-analyses and creating an undesired heterogeneity of outcomes. The harmonisation of response assessment is therefore an important unmet need in GCA research. In this viewpoint article, we discuss the challenges and opportunities with the development of new, internationally accepted response criteria. A change of disease activity is a fundamental component of response; however, it is debatable whether the ability to taper GC and/or the maintenance of a disease state for a specific time period, as applied in recent RCTs, should be part of response assessment. The role of imaging and novel laboratory biomarkers as possible objective markers of disease activity needs further investigation but might be a possibility when drugs directly or indirectly influence the levels of traditional acute-phase reactants such as erythrocyte sedimentation rate and C reactive protein. Futures response criteria might be constructed as a multidomain set, but the questions about which domains will be included and what their relative weights will be still need to be answered.
Subject(s)
Giant Cell Arteritis , Humans , Giant Cell Arteritis/drug therapy , Treatment Outcome , Glucocorticoids/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). METHODS: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. RESULTS: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. CONCLUSIONS: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.
ABSTRACT
OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.
ABSTRACT
OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.
Subject(s)
Giant Cell Arteritis , Humans , Giant Cell Arteritis/diagnostic imaging , Carotid Intima-Media Thickness , Reproducibility of Results , Prospective Studies , Temporal Arteries/diagnostic imaging , Ultrasonography/methodsABSTRACT
BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.
Subject(s)
Inflammation , Receptors, Interleukin-6 , Adult , Humans , Arthritis, Rheumatoid/drug therapy , COVID-19 , Interleukin-6 , Receptors, Interleukin-6/antagonists & inhibitors , Still's Disease, Adult-Onset/drug therapy , Inflammation/drug therapyABSTRACT
Telemedicine is increasingly used in rheumatology. While telemedicine guaranteed care of patients during the COVID-19 pandemic, it is now increasingly used to facilitate triage of patients, monitoring of disease activity, and patients' education. In addition, tele-visits as well as remote physio- and psychotherapy are replacing traditional face-to-face contacts between patients and their healthcare provider. While this may save resources in a world in which the gap between the demand and the provision of healthcare increases, there is also a danger of losing essential information, for example by non-verbal communication, that can only be retrieved during face-to-face contact in the office. In addition, it may be challenging to build a trusting relationship between patients and healthcare professionals by virtual means only. Globally acting companies that see market opportunities already amply offer 'simple' technical solutions for telemedicine. While such solutions may seem (economically) interesting at first glance, there is a risk of monopolization, leaving the most valuable parts of healthcare to a small number of profit-seeking companies. In this article, the opportunities and threats of telemedicine in rheumatology are debated. A possible way forward is to complement traditional face-to-face visits with information gained by telemedicine, in order to render these consultations more efficient rather than replacing personal contact by technology.
Subject(s)
COVID-19 , Rheumatology , Telemedicine , Humans , COVID-19/epidemiology , Pandemics , Delivery of Health CareABSTRACT
OBJECTIVES: The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. METHODS: A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). RESULTS: Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19-1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: -0.23; -0.43 to -0.03), function (HAQ -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. CONCLUSION: There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.
Subject(s)
Arthritis, Rheumatoid , Glucocorticoids , Humans , Glucocorticoids/adverse effects , Arthritis, Rheumatoid/drug therapy , Prednisone/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To investigate the clinical manifestations and outcome of COVID-19 in patients with inflammatory rheumatic and musculoskeletal disease (iRMD) as compared with the general population. METHODS: This is a case-control study of patients selected from the South-Tyrol public health service-Italy with and without iRMD affected by COVID-19. We included patients ≥18 years and with a positive SARS-CoV-2 PCR test between 1.10.2020 and 01.03.2021. Cases were identified by linking the diagnosis of a rheumatic disease with PCR test positivity; these were matched in a 1:1.8 (planned 1:2) ratio for age, sex, and date of COVID-19 diagnosis with people from the general population. The outcomes of primary interest were hospitalization and severe course (intensive care unit, mechanical ventilation/extracorporeal membrane oxygenation, death). RESULTS: The study population consisted of 561 COVID-19 patients, of which 201 (mean age 60.4 years; 65.2% female) were patients with iRMD and 360 were controls from the general population (59.8 years; 64.7% female). The majority of iRMD patients (88.6%) received an immunosuppressive drug at time of COVID-19 diagnosis, 36.3% were under glucocorticoids. COVID-19 related hospitalization (12.4% vs 10.6%, p= 0.49), severe course (5.0% vs 5.3%, p= 1.00), and mortality (3.5% vs 4.4%, p= 0.66) were similar between groups. Among hospitalized patients, mechanic ventilation was more common in iRMD patients than in controls [n = 5 (20.0%) vs n = 1 (2.6%), p= 0.035]. CONCLUSIONS: Our study indicates similar rates for admission, severe course and mortality between patients with iRMD and controls affected by COVID-19. Among hospitalized patients, mechanical ventilation was more frequently required in the iRMD group.
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OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.
Subject(s)
General Practitioners , Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/drug therapy , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Rheumatologists , Glucocorticoids/therapeutic use , Prednisolone/therapeutic use , Surveys and QuestionnairesABSTRACT
OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Lung Diseases, Interstitial , Microscopic Polyangiitis , Rheumatology , Humans , Microscopic Polyangiitis/complications , Microscopic Polyangiitis/diagnostic imaging , Microscopic Polyangiitis/epidemiology , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnostic imaging , Granulomatosis with Polyangiitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , Cross-Sectional Studies , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/epidemiology , Lung Diseases, Interstitial/etiology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Myeloblastin , Demography , PeroxidaseABSTRACT
Aortic dilatation (AD) occurs in up to 30% of patients with giant cell arteritis (GCA). Reliable biomarkers for AD development, however, are still absent. The aim of this exploratory study was to evaluate whether immunological parameters are associated with the occurrence of AD in GCA. Cross-sectional study on 20 GCA patients with AD, 20 GCA patients without AD, and 20 non-GCA controls without AD measuring leukocytes, neutrophils, lymphocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), interferon (IFN)-α, IFN-γ, IFN-γ-induced protein 10 (IP-10), interleukin (IL) 5, IL-8, IL-10, IL-17A, IL-18, IL-1 receptor antagonist, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF), L-selectin, P-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1). AD was measured by aortic contrast-enhanced computed tomography and defined by enlargement of the aorta above population-based aortic diameters adjusted by age, gender, and body surface area. No significant differences were observed between GCA patients with AD and GCA patients without AD concerning levels of leukocytes, neutrophils, lymphocytes, CRP, ESR, SAA, IL-8, IL-18, PDGF, IP-10, selectins, and sICAM-1. Values of IFN-α, IFN-γ, IL-5, IL-10, IL-17A, IL-1 receptor antagonist, and TNF-α were all below the detection limits in more than 70% of subjects. Lymphocytes and CRP revealed positive correlations with the diameter of the thoracic descending aorta. Immunological parameters were not useful to conclude on the presence of AD in GCA. Further studies are required to test if CRP and lymphocytes may be useful to predict future development of AD in GCA.
Subject(s)
Aortic Diseases , Giant Cell Arteritis , Humans , Giant Cell Arteritis/diagnosis , Interleukin-10 , Interleukin-18 , Interleukin-17 , Cross-Sectional Studies , Chemokine CXCL10 , Dilatation , Interleukin-8 , C-Reactive Protein/analysis , Tumor Necrosis Factor-alpha , Receptors, Interleukin-1ABSTRACT
The Arab League of Associations for Rheumatology (ArLAR) Research Group (ARCH) conducted this study to investigate the number of current practicing rheumatologists in the Arab countries, to estimate the projected number of rheumatologists in 10 years, and to evaluate the current workload, practice profile, consultation waiting time, and geographical mobilities of these rheumatologists. This cross-sectional survey study was conducted in 16 Arab countries in two parts. The first survey was addressed nominally to national societies to estimate the current and projected workforce. The second was an anonymous e-survey elaborated by the study steering committee on the Google Forms platform and distributed to Arab rheumatologists using social media, WhatsApp, and mass e-mails to evaluate their practice. The mean number of rheumatologists in Arab countries was 0.84 per 100,000 inhabitants (mean age 47.5 years, 55% females), ranging from 0.06 (Sudan) to 1.86 (Tunisia). The number of rheumatologists is expected to increase by 50% in 2032. Nevertheless, a 20% increase in population associated with an increase in demand is also expected. Data from 446 rheumatologists (mean age 43.9 years, 60.5% females) revealed that 72% worked full-time, and 53% were employed in the public sector only. The average waiting time for a rheumatology consultation was 19.9 days. Of 394 rheumatologists, 19% obtained their rheumatology diplomas from non-Arab countries, and 47% of Gulf rheumatologists were non-citizen physicians. Considering local demographic disparities, healthcare system differences, and geographical mobilities, national authorities are advised to implement effective intervention plans to optimize the rheumatology workforce.
ABSTRACT
Polymyalgia rheumatica (PMR) is the second most frequent inflammatory rheumatic disease in old age. Remission and recurrence are frequently used as endpoints in clinical trials; however, there is as yet no international consensus on the definition of these states, which limits the comparability of published studies. The PMR activity score (PMR-AS) is the only composite score specifically developed for PMR, which together with remission is used to define low, middle and high disease activity. In recent studies the PMR-AS was often used and low disease activity was established as endpoint. The most important limitation of the PMR-AS is the potential influence of the individual variables by comorbidities. The value of Creactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are of restricted value in studies using drugs that influence the interleukin 6 (IL-6) axis. In these cases, calprotectin and osteopontin are promising alternative biomarkers, as they have already been shown to reflect disease activity independently of CRP in rheumatoid arthritis. Furthermore, imaging modalities including sonography, magnetic resonance imaging and fluorodeoxyglucose (FDG) positron emission tomography could also be helpful in monitoring disease activity; however, these techniques must first be validated in further studies. The PMR impact scale (PMR-IS) is a composite score to assess the impact of PMR on the patients; however, it has not yet been used in clinical studies. The development of additional patient reported outcomes (PRO) for PMR and the definition of standardized criteria for documentation of remission and recurrence are important questions in the future research agenda for PMR.
Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Biomarkers , Blood Sedimentation , C-Reactive Protein/analysisABSTRACT
BACKGROUND: Polymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed. METHODS: In this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks.The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated. RESULTS: From 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721-842) mg and 935 (861-1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient. CONCLUSION: In patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose. TRIAL REGISTRATION NUMBER: NCT03263715.
Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Antibodies, Monoclonal, Humanized , Drug Administration Schedule , Giant Cell Arteritis/drug therapy , Glucocorticoids , Humans , Polymyalgia Rheumatica/chemically induced , Polymyalgia Rheumatica/drug therapy , Recurrence , Treatment OutcomeABSTRACT
OBJECTIVES: Inflammatory rheumatic and musculoskeletal diseases (iRMDs) are associated with increased systemic bone loss that is mediated by chronic inflammation, treatment with glucocorticoids (GCs) and other factors. Our objective was to analyse the impact of variables that influence osteoporosis (OP) in patients with iRMD treated with GC. METHODS: Rh-GIOP (acronyme) is a prospective observational cohort study investigating bone health in consecutive patients with iRMD and current or prior GC treatment. We present an analysis of the patients' baseline data here. Bone mineral density (BMD) measured by dual X-ray absorptiometry was the primary outcome. Multivariable linear regression models were performed to identify variables associated with BMD. RESULTS: Data from 1066 patients with iRMD were analysed. GC doses of <5 mg prednisone equivalent per day, cumulative dose and duration of GC therapy were not associated with negative effects on BMD. Dosages of ≥5 mg/day lost their negative association with BMD after adjustment for confounders. When subanalysing patients with exactly 5 mg/day, no negative effect was seen. For patients with rheumatoid arthritis (RA), GC doses of >7.5 mg/day showed a negative association with BMD overall, but this effect seemed to be specific only to patients with moderate or high disease activity (Disease Activity Score 28-C reactive protein >3.2). CONCLUSIONS: GCs of ≤5 mg/day did not seem to be associated with a reduction of BMD in patients with iRMD and current or prior exposure to GC. This is most likely due to the dampening of inflammation by GC, which exerts a mitigating effect on the risk of OP. In RA, current GC doses of >7.5 mg/day were negatively associated with BMD, but only in patients with moderate to high disease activity. TRIAL REGISTRATION NUMBER: NCT02719314.