Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

OBJECTIVES: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. METHODS: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. RESULTS: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. CONCLUSION: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.

Incidence of primary large vessel vasculitis in Norfolk, UK from 2011 to 2020.

OBJECTIVES: To report the annual incidence of primary large vessel vasculitis (LVV) in the adult population of Norfolk County, UK, including giant cell arteritis (GCA) (in those ≥50 years) and Takayasu arteritis (TAK). METHODS: Individuals diagnosed by histology or imaging who lived in NR1-NR30 postcode districts were included. Validated criteria from 1990 and 2022 were applied for final classification. Population data were available from the Office of National Statistics, UK. RESULTS: 270 individuals were diagnosed with primary LVV over 4.7 million person-years. The annual incidence (95% CI) of primary LVV was 57.5 (50.8, 64.7)/million person-years in the adult population. 227 and 244 individuals were diagnosed with GCA over ~2.5 million person-years using 1990 and 2022 criteria, respectively. The annual incidence (95% CI) of GCA was 91.6 (80.0, 104.3)/million person-years aged ≥50 years using 1990 criteria and 98.4 (86.4, 111.6)/million person-years aged ≥50 years using 2022 criteria. 13 and 2 individuals were diagnosed with TAK over 4.7 million person-years. The annual incidence (95% CI) of TAK was 2.8 (1.5, 4.7)/million person-years using 1990 criteria and 0.4 (0.0, 1.4)/million person-years using 2022 criteria, in the adult population. The incidence of GCA rose sharply in 2017 coincident with the introduction of a fast-track pathway and fell during the pandemic when the pathway was disrupted. CONCLUSIONS: This is the first study that reports the incidence of objectively verified primary LVV in the adult population. The incidence of GCA may be affected by the availability of diagnostic pathways. The use of the 2022 classification criteria results in a rise in the classification of GCA and fall in that of TAK.

Disease stratification in GCA and PMR: state of the art and future perspectives.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related conditions characterized by systemic inflammation, a predominant IL-6 signature, an excellent response to glucocorticoids, a tendency to a chronic and relapsing course, and older age of the affected population. This Review highlights the emerging view that these diseases should be approached as linked conditions, unified under the term GCA-PMR spectrum disease (GPSD). In addition, GCA and PMR should be seen as non-monolithic conditions, with different risks of developing acute ischaemic complications and chronic vascular and tissue damage, different responses to available therapies and disparate relapse rates. A comprehensive stratification strategy for GPSD, guided by clinical findings, imaging and laboratory data, facilitates appropriate therapy and cost-effective use of health-economic resources. Patients presenting with predominant cranial symptoms and vascular involvement, who usually have a borderline elevation of inflammatory markers, are at an increased risk of sight loss in early disease but have fewer relapses in the long term, whereas the opposite is observed in patients with predominant large-vessel vasculitis. How the involvement of peripheral joint structures affects disease outcomes remains uncertain and understudied. In the future, all cases of new-onset GPSD should undergo early disease stratification, with their management adapted accordingly.

Remitting Seronegative Symmetrical Synovitis with Pitting Oedema Following Administration of the Chadox1-S/NCOV-19 Coronavirus Vaccine.

Introduction: We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome following administration of the ChAdOx1-S/nCoV-19 [recombinant] vaccine, suggesting a possible causal link. Case Description: A 72-year-old man presented to his general practitioner with swollen, oedematous hands and legs 2 weeks after receiving a coronavirus vaccine. He had raised inflammatory markers but remained systemically well. He was initially presumed to have cellulitis, but his symptoms persisted despite several courses of antibiotics. Deep vein thromboses, cardiac failure, renal failure and hypoalbuminaemia were ruled out. Upon Rheumatology review, he was diagnosed as having RS3PE syndrome with the Covid vaccine suspected of being an immunogenic trigger. Following initiation of steroid therapy, his symptoms improved dramatically, as is characteristic of RS3PE syndrome. Discussion: The pathophysiology of RS3PE is unclear. It is known to have various triggers and associations including infections, certain vaccines and malignancy. This case highlights that a coronavirus vaccine (ChAdOx1-S/nCoV-19 [recombinant] vaccine) is also a possible trigger. Factors that make the diagnosis likely include an acute onset of symptoms including pitting oedema in a typical distribution, age above 50, and unremarkable autoimmune serology. Other learning points from this case include the importance of antibiotic stewardship and the need to explore non-infectious causes of illness when antibiotics do not improve symptoms. Conclusion: The ChAdOx1-S/nCoV-19 [recombinant] vaccine is a possible trigger of RS3PE. However, the benefits of vaccines against coronavirus outweigh the risks in the majority of patients. LEARNING POINTS: This case demonstrates a possible link between the ChAdOx1-S/nCoV-19 [recombinant] vaccine and autoimmune conditions such as RS3PE.It is important to consider alternative diagnoses when antibiotic regimes fail to work.A barrier to accurate diagnosis includes an episodic approach, where a patient presents to multiple clinicians acutely rather than having a long-term, continuous relationship with a single multi-disciplinary team, where response to treatment can be monitored.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

Diagnostic delay is common for patients with axial spondyloarthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Updated guidelines for patients with axial SpA (axSpA) have sought to reduce diagnostic delay by raising awareness among clinicians. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe baseline characteristics and time to diagnosis for newly referred patients with axSpA in England and Wales. METHODS: Analyses were performed on sociodemographic and clinical metrics, including time to referral and assessment, for axSpA patients (n = 784) recruited to the NEIAA between May 2018 and March 2020. Comparators were patients recruited to the NEIAA with RA (n = 9270) or mechanical back pain (MBP; n = 370) in the same period. RESULTS: Symptom duration prior to initial rheumatology assessment was longer in axSpA than RA patients (P < 0.001) and non-significantly longer in axSpA than MBP patients (P = 0.062): 79.7% of axSpA patients had symptom durations of >6 months, compared with 33.7% of RA patients and 76.0% of MBP patients. Following referral, the median time to initial rheumatology assessment was longer for axSpA than RA patients (36 vs 24 days; P < 0.001) and similar to MBP patients (39 days; P = 0.30). Of the subset of patients deemed eligible for early inflammatory arthritis pathway follow-up, fewer axSpA than RA patients had disease education provided (77.5% vs 97.8%) and RA patients reported a better understanding of their condition and treatment. CONCLUSION: Diagnostic delay in axSpA remains a major challenge despite improved disease understanding and updated referral guidelines. Disease education is provided to fewer axSpA than RA patients, highlighting the need for specialist clinics and support programmes for axSpA patients.

Maxillary artery involvement in giant cell arteritis demonstrated by ultrasonography.

We describe two cases of giant cell arteritis where involvement of the superficial temporal artery and maxillary artery were demonstrated using colour doppler ultrasonography. Maxillary artery involvement is responsible for the symptoms of jaw claudication and toothache, and even headaches might be due to the involvement of the middle meningeal artery which is a branch of the maxillary artery. The maxillary artery has been difficult to visualise until now. There are international consensus definitions of ultrasonographic abnormalities seen in the superficial temporal artery affected by giant cell arteritis. We have used those definitions to demonstrate hypoechoic changes in the maxillary artery affected by giant cell arteritis. The maxillary artery can be visualised in the infratemporal fossa from an echo window between the condylar and coronoid processes of the mandible. This is the first proof of concept evidence that maxillary arteries can be visualised using bedside ultrasonography in giant cell arteritis.

Role of the halo sign in the assessment of giant cell arteritis: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA. METHODS: A systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model. RESULTS: The initial search yielded 4023 studies. Twenty-three studies (patients n = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95). CONCLUSION: The US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice. REGISTRATION: PROSPERO 2020 CRD42020202179.

Inflammatory back pain: a concept, not a diagnosis.

PURPOSE OF REVIEW: The concept of inflammatory back pain (IBP) describes a cohort of patients with chronic back pain (CBP) who have distinct clinical characteristics, rather than being a diagnosis in and of itself. IBP is a common and important feature of axial spondyloarthritis (axSpA) but this is not the only differential. This review examines the utility of IBP in both primary and secondary care settings. RECENT FINDINGS: There are a number of suggested referral strategies for patients with suspected axSpA that include IBP. These strategies attempt to strike a balance between ensuring potential axSpA patients are not overlooked, whilst simultaneously not overwhelming secondary care services. Their success relies on the clinicians who first encounter these patients being familiar with IBP as a concept; however, it is still poorly recognized by many healthcare professionals. IBP may be helpful as part of a referral strategy; however, other clinical features, laboratory investigations and radiology must be incorporated for the final diagnostic outcome in axSpA. SUMMARY: Delayed diagnosis is a major clinical problem in axSpA and is associated with worse clinical outcomes. When recognized and utilized correctly, IBP can be a useful tool to promote prompt referral to rheumatology services.

Ultrasonography in the diagnosis and follow-up of giant cell arteritis.

Colour Doppler ultrasonography is the first measure to allow objective bedside assessment of GCA. This article discusses the evidence using the OMERACT filter. Consensus definitions for ultrasonographic changes were agreed upon by a Delphi process, with the 'halo' and 'compression' signs being characteristic. The halo is sensitive to change, disappearing within 2-4 weeks of starting glucocorticoids. Ultrasonography has moderate convergent validity with temporal artery biopsy in a pooled analysis of 12 studies including 965 participants [κ = 0.44 (95% CI 0.38, 0.50)]. The interobserver and intra-observer reliabilities are good (κ = 0.6 and κ = 0.76-0.78, respectively) in live exercises and excellent when assessing acquired images and videos (κ = 0.83-0.87 and κ = 0.88, respectively). Discriminant validity has been tested against stroke and diabetes mellitus (κ=-0.16 for diabetes). Machine familiarity and adequate examination time improves performance. Ultrasonography in follow-up is not yet adequately defined. Some patients have persistent changes in the larger arteries but these do not necessarily imply treatment failure or predict relapses.

Halo score (temporal artery, its branches and axillary artery) as a diagnostic, prognostic and disease monitoring tool for Giant Cell Arteritis (GCA).

BACKGROUND: Giant cell arteritis (GCA) is a common large vessel vasculitis of the elderly, often associated with sight loss. Glucocorticoids (GC remain the mainstay of treatment, although biologic treatments have been approved. Biomarkers predicting disease severity, relapse rates and damage are lacking in GCA.EULAR recommends ultrasound (US) as the first investigation for suspected GCA. The cardinal US finding, a non-compressible halo, is currently categorised as either negative or positive. However, the extent and severity of this finding may vary.In this study, we hypothesise whether the extent and severity of the halo sign [calculated as a single composite Halo score (HS)] of temporal and axillary arteries may be of diagnostic, prognostic and monitoring importance; whether baseline HS is linked to disease outcomes, relapses and damage; whether HS can stratify GCA patients for individual treatment needs; whether HS can function as an objective monitoring tool during follow up. METHODS: This is a prospective, observational study. Suspected GCA Participants will be selected from the GCA FTC at the participating centres in the UK. Informed consent will be obtained, and patients managed as part of standard care. Patients with GCA will have HS (temporal and axillary arteries) measured at baseline and months 1,3,6 and 12 long with routine clinical assessments, blood sampling and patient-reported outcomes (EQ5D). Non-GCA patients will be discharged back to the referral team and will have a telephone interview in 6 months.We aim to recruit 272 suspected GCA referrals which should yield 68 patients (25% of referrals) with confirmed GCA. The recruitment will be completed in 1 year with an estimated total study period of 24 months. DISCUSSION: The identification of prognostic factors in GCA is both timely and needed. A prognostic marker, such as the HS, could help to stratify GCA patients for an appropriate treatment regimen. Tocilizumab, an IL-6R blocking agent, switches off the acute phase response (C-Reactive Protein), making it difficult to measure the disease activity. Therefore, an independent HS, and changes in that score during treatment and follow-up, maybe a more objective measure of response compare to patient-reported symptoms and clinical assessment alone.

A probability score to aid the diagnosis of suspected giant cell arteritis.

OBJECTIVES: We propose a GCA probability score intended to help to risk-stratify patients referred by general practitioners with suspected GCA into those with high probability of GCA versus low probability of GCA. In this pilot study we evaluated the diagnostic accuracy of this proposed scoring system. METHODS: A scoring system was proposed based on clinical experience. Retrospective analysis was conducted from clinical notes of consecutive patients presenting to a Fast Track Pathway clinic between August 2016 and August 2017. The GCA Probability Score was calculated for each patient and receiver operating characteristic (ROC) curve plotted. RESULTS: Of 122 consecutive patients, full data were available for calculation of GCA probability score in all patients except one (excluded from this analysis). The area under the ROC curve was 0.953 (95% confidence interval: 0.911, 0.994). The ROC curve showed an optimal cut point of 9.5 out of a possible score of 32. At this cut-point there was a sensitivity of 95.7% and specificity 86.7%, and 88.4% of cases were correctly classified. CONCLUSIONS: The GCA Probability Score is a promising and feasible tool for risk stratification of patients referred by general practitioners with suspected GCA. In a fast track clinic setting this aids exclusion of GCA in low probability cases and confirmation of disease in high probability disease. Refinement and subsequent external validation of this score is required.