Navigating Giant Cell Arteritis (Gca) Service during and Post Covid-19 Pandemic: An Audit of Gca Care at North Bristol Nhs Trust against the Bsr Quality Standards

Background/Aims GCA is a systemic vasculitis predominantly affecting the large vessels that requires prompt diagnosis and management. This clinical audit aims to study the impacts of COVID-19 pandemic on our GCA service and to identify areas for improvement to ensure good and safe practice amid healthcare crisis. Methods We audited referrals for suspected GCA from February 2021 until September 2022 and measured our patient care against the BSR quality standards. We performed retrospective data collection from digital care record systems and analysed our data using the IBM SPSS Statistics version 29. Results 106 patients with suspected GCA were included, 73% were female and the mean age was 70 years. 75% of the referrals were from primary care. Main presenting symptoms were headaches (95.7%), scalp tenderness (69.6%), tongue/jaw claudication (52.2%), visual symptoms (47.8%), constitutional symptoms (43.5%) and polymyalgic symptoms (21.7%). 33% of patients were diagnosed and treated as GCA. Mean CRP was 23.9mg/L and mean plasma viscosity was 1.89mPA. The mean referral-to-specialist review time has reduced to 1.6 days, compared with 2.7 days pre-pandemic. All patients had vascular ultrasound but only 7.5% had a temporal artery biopsy (TAB), compared with 41% pre-pandemic. Table 1 compares expected and achieved BSR quality standards. Conclusion Changes in work pattern during the pandemic meant that the time from referral to specialist review was significantly reduced, by implementing twice weekly registrar-led 'Hot' clinics and reserving ad hoc slot(s) in on-call consultant's clinics for GCA referrals. We have ramped up our vascular imaging capacity for vascular ultrasound during the pandemic in response to reduced surgical operating capacity for TAB. Strategies to address areas for improvement identified in this audit include: (1) clear and timely communication with referrer about steroid initiation and dosage, at the time of referral;(2) improving communication with primary care, emphasising need for urgent Ophthalmology input in patients with suspected GCA-related visual symptoms, through updating our regional GCA guideline for primary care;(3) standardising and implementing a GCA review proforma or checklist in our department to ensure that the BSR GCA care bundle is being implemented and addressed at the earliest opportunity. (Table Presented).

Challenges in the Diagnosis and Investigation of Giant Cell Arteritis during Covid- 19 Pandemic Restrictions: Does the Southend Pretest Probability Score Help to Guide Clinical Diagnosis?

Background/Aims During 2020-2021 many usual hospital services were affected as focus turned towards managing COVID-19. Elective outpatient surgery ceased and rheumatology staff were redeployed to covid wards. This reduced the availability of temporal artery biopsy (TAB) and temporal artery ultrasound (TAUS) to aid in diagnosing giant cell arteritis (GCA). The rheumatology team making diagnoses of GCA or not-GCA were doing so often based entirely on clinical and laboratory findings. We aimed to determine referral patterns and investigations for suspected GCA during the covid pandemic, compare diagnoses at 6 months after initial assessment and retrospectively apply the Southend Pretest Probability Score (PTPS) and correlate with the diagnosis of GCA or not-GCA. Methods We reviewed all electronic referrals for suspected GCA from July 2020 - June 2021. Clinical details and investigations reviewed. PTPS applied giving a result of low, intermediate or high probability of GCA. Results 84 referrals for suspected GCA over 12 months. 20 diagnosed GCA/ large vessel vasculitis (LVV), 64 not-GCA. Peak referral months Nov 2020 and April 2021 with 13 and 16 referrals. Lowest in October 2020 with 1 referral. 57 female, 27 male. Mean age 70.1 years. 19% male referrals diagnosed GCA, 26% female diagnosed GCA. All LVV and PMR diagnoses were female. 27 TAUS, 6 TAB, 7 PET, 13 CT, 3 MRI performed. 30 patients had no additional investigations. Of 20 GCA;14 had supporting investigations, 6 were clinical diagnoses. All GCA diagnoses were consistent at 6 months. One not-GCA case was subsequently diagnosed with LVV on CTPET. All other not-GCA diagnoses were consistent at 6 months. The PTPS was retrospectively applied based on available clinical information in all except 2 cases, and compared to GCA/not-GCA diagnosis and investigations undertaken. Conclusion Referral numbers for suspected GCA were higher than previous years however the number of actual GCA diagnoses was similar. With limitations on diagnostic investigations due to covid, diagnoses of GCA with and without additional tests were accurate at 6 months, and correlated with a high probability score. The PTPS is a therefore valuable clinical tool in the assessment of GCA. (Table Presented).

Trends in California ophthalmology surgical volume during the COVID pandemic

Purpose : Pandemic era restrictions on non-essential travel, redistribution of healthcare resources, and nursing shortages have impacted the ability of ophthalmologists to deliver care. California had among the strictest 2020 restrictions during the pandemic with reallocation of non-essential surgical resources. This study assesses changes in surgical volume of common ophthalmic procedures in California since the COVID-pandemic. Methods : The California Health and Human Services Agency (Office of Statewide Health Planning & Development) maintains ambulatory and emergency room procedural databases. Common ophthalmic procedures and surgical volumes were extracted for 29 CPT codes from 2014-2020. Procedures with fewer than 100 cases were excluded. Results : Overall, ophthalmology surgical volume decreased by 19% from 2019 to 2020. Greatest declines were for anterior lamellar corneal transplant (39%) and pterygium with graft (38%). Simple cataract surgeries declined by 29% in 2020, compared to an average annual decline of 3% from 2014-2019. Volume increased only for two surgeries: aqueous shunt with graft (2%) and complex retinal detachment (0.2%). Temporal artery biopsies, historically stable with 0.2% average change from 2014-2019, declined by 28% in 2020. Retinal detachment repairs declined by 20% and 17% (with and without vitrectomy, respectively). In comparison, laparoscopic appendectomy only declined by 2% in 2020. Limitations of this study include role of population changes and changes in annual coding practices. Conclusions : COVID era declines were noted across almost all ophthalmic surgeries with steep drops in perceived non-urgent procedures such as pterygium and cataract. However, delays in cataracts and other conditions can result in increased disease burden and morbidity for patients. Uniquely, tube shunt procedures increased, perhaps due to progression of glaucoma from delayed routine care. For vision-preserving surgeries such as retinal detachment repair, lack of accessible care during the pandemic is especially concerning.

TOCILIZUMAB for GIANT CELL ARTERITIS: BASELINE and TWELVE MONTH AUDIT DATA from the UK BRISTOL and BATH MULTIDISCIPLINARY MEETING

Background: Giant Cell Arteritis (GCA) is a systemic vasculitis involving large and medium-sized blood vessels. Treatment is with high dose glucocorticoids. Steroid-sparing agents and Tocilizumab (TCZ) are used for refractory or relapsing cases. NHS England requires all GCA patients to be discussed in a regional multidisciplinary team meeting (MDT) prior to commencing TCZ. TCZ has only been permitted for a maximum of one year;this time limitation was extended during the Covid-19 pandemic (1). The monthly virtual Bristol and Bath regional MDT started in November 2018. Objectives: We aimed to review: 1) Baseline data on all patients referred to the Bristol and Bath TCZ for GCA MDT, including demographics, clinical presentation and previous steroid-sparing agents used and 2) 12 month follow up data including number of completions, adverse effects, and fares on treatment. Methods: The TCZ MDT referral proforma, adapted from the NHS England Blueteq approval form, was reviewed for all patients referred. 12 month follow up data was obtained from clinic letters. Results: Baseline data Thirty-eight cases were referred between November 2018 and September 2021. Of these, 31 were approved for TCZ usage;100% fulflled the criteria for either refractory (n=11) or relapsing (n=20) disease. Mean age was 74 years and 74.2% were female. Average disease duration was 161.5 days for the refractory and 827.3 days for the relapsing group. 77.4% had cranial GCA, 48.4% had large vessel involvement, 45.2% had visual symptoms and 25.8% had ischaemic visual loss. The positive investigations were PET-CT (48.4%), temporal artery ultrasound (41.9%) and temporal artery biopsy (32.3%). 64.5% had trialled a steroid-sparing agent at time of referral (61.3 % metho-trexate, 9.7% azathioprine, 6.5% lefunomide), 35.5% had received intravenous methylprednisolone and 58% were receiving greater than 40mg prednisolone at the time of referral. Glucocorticoid adverse effects of osteoporosis, weight gain, cataracts and hypertension were each seen in 19.4%;whilst diabetes, neuropsychiatric symptoms and sleep disturbance were each reported in 16.1%. Those with ocular involvement tended to be referred earlier than those without (478.2 days vs 648.1 days), were referred on higher doses of glucocorticoids (71.4% vs 47.1% on ≥ 40mg) and had less steroid-sparing agents prior to referral. Follow up data In December 2021, a follow-up audit revealed 14/31 patients had completed at least 12 months of tocilizumab;5 of these had had an extension under Covid-19 exceptional guidance (mean duration of 5.2 months). Of the remaining 17: 3 patients had stopped early (1 death, 1 moved away, 1 due to adverse effects of headache and gastro-intestinal side effects), 4 had not started tocilizumab and 10 had not completed 12 months of treatment at that point. Adverse events in the 14 patients at 12 months included: liver abnormalities (2/14;14.3%), neutropenia (2/14;14.3%), thrombocytopaenia (1/14;7.1%), soft tissue infections (3/14;21.4%), urinary tract infection (1/14;7.1%) and lipid derangement (4/14 28.6%). One case of GCA relapse occurred on TCZ (mild headache and raised infammatory markers settled on small increase in prednisolone). After 12 months, mean prednisolone dose was 3mg (range 0-15mg). Conclusion: All patients approved for Tocilizumab in the GCA MDT fulflled NHS England criteria for either relapsing or refractory disease. The majority of cases had cranial disease, but almost half had either ocular or large vessel involvement, refecting a severe spectrum of disease. Cases showed a high burden of glucocorticoid toxicity. Follow up data suggests that TCZ was effective in allowing glucocorticoid weaning and disease control, but with some adverse effects. Future work to follow up patients after stopping Tocilizumab would be informative, as the twelve month limitation on treatment is likely to be re-instated.

TOCILIZUMAB in COMBINATION with 8 WEEKS of PREDNISONE for GIANT CELL ARTERITIS

Background: Even with the use of tocilizumab (TCZ), signifcant glucocorticoid exposure (usually ≥ 6 months) continues to be an important problem in giant cell arteritis (GCA). Objectives: We aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in combination with 2 months of prednisone in a group of patients with GCA. Methods: We conducted a prospective, single arm, open-label study of TCZ in combination with 2 months of prednisone for new-onset and relapsing GCA patients with active disease (ClinicalTrials.gov Identifer NCT03726749). GCA diagnosis required confrmation by temporal artery biopsy or vascular imaging. Active disease was defned as presence of cranial or polymyalgia rheumat-ica symptoms necessitating treatment within 6 weeks of baseline. All patients received TCZ 162 mg subcutaneously every week for 12 months and an 8-week prednisone taper starting between 20 mg and 60 mg daily (Figure 1). The primary endpoint, sustained prednisone-free remission, was defned as absence of relapse from induction of remission up to week 52 while adhering to the prednisone taper. Relapse was defned as the recurrence of symptoms of GCA requiring treatment intensifcation regardless of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Safety was also evaluated. 8-week prednisone taper starting between 20 mg and 60 mg Primary endpoint Prednisone-free remission at week 52 Figure 1. Clinical Trial Schema Results: Between 11/2018 and 11/2020 we enrolled 30 patients (mean age 74 years, 60% females, 50% new-onset disease, 77% temporal artery biopsy-proven, 47% imaging-proven). The mean ESR and CRP at screening were 45 mm/hour and 48 mg/L, respectively. The initial prednisone dose was 60 mg (n = 7), 50 mg (n = 1), 40 mg (n = 7), 30 mg (n = 6) and 20 mg (n = 9). All patients entered remission within 4 weeks of baseline. The primary endpoint was achieved by 23 (77%) patients (Table 1). The mean (SD) cumulative prednisone dose in these 23 patients was 1052 (390) mg. After a mean period of 16 weeks, 7 (23%) patients relapsed (Table 1). All relapses but one occurred after the completion of the study prednisone taper. Overall, 6 of the 7 patients with relapse received a second prednisone taper over 8 weeks. Of these 6 patients, 4 achieved and maintained remission for the remainder of the trial period, and 2 withdrew from the study after having a second relapse. One patient with relapse received a second prednisone taper over 26 weeks and stayed in remission until the end of the study. The mean (SD) cumulative prednisone dose in the 7 patients with relapse was 1883 (699) mg (Table 1). Overall, 4 (13%) participants developed a serious adverse event (Table 1). No cases of ischemia-related visual symptoms including permanent vision loss occurred during the study. Table 1. Efficacy and Safety Outcomes GCA patients (n = 30) Efficacy Sustained, prednisone-free remission by week 52 23.0 (76.7) Cumulative prednisone dose (mg) at week 52, mean (SD) 1051.5 (390.3) Relapse 70 (23.3) Time to relapse, weeks: mean (SD) 15.8 (14.7) Prednisone dose (mg/day) at relapse, mean (SD) 2.1 (5.2) Cumulative prednisone dose (mg), mean (SD) 1883.1 (699.2) Clinical manifestations at relapse Cranial symptoms 4 out of 7 patients schemic visual symptoms 0 out of 7 patients PMR symptoms 4 out of 7 patients Safety Serious adverse events 4.0 (13.3) Cellulitis 1 COVID-19 1 Fragility fracture 1 Cholecystitis 1 Values represent number and (%) unless otherwise specifed. SD, standard deviation;PMR, polymyalgia rheumatica Conclusion: These results suggest that 12 months of TCZ in combination with 8 weeks of prednisone could be efficacious for inducing and maintaining disease remission in patients with GCA. Confrmation of these fndings in a randomized controlled trial is required.

GIANT CELL ARTERITIS-RELATED STROKE in A MAN with ELDERLY-ONSET RHEUMATOID ARTHRITIS

Background: Giant cell arteritis-related stroke is rare, with high early mortality and major morbidity in survivors. Objectives: To increase the awareness of coexistence of giant cell arteritis-re-lated stroke and rheumatoid arthritis. Methods: A case report and discussion. Results: A 73 year-old man with seronegative elderly-onset rheumatoid arthritis (EORA) presented to the emergency department (ED) with a one week history of frontal headache, vomiting and dizziness. He had multiple cardiovascular comor-bidities and took multiple medications, including methotrexate and sulfasalazine. He also had long-standing history of thrombocytopenia without requiring any treatment. Neurological examination performed in the ED was unremarkable. His C-reactive protein (CRP) was 69mg/L and erythrocyte sedimentation rate (ESR) 82mm/hour. Computed tomography (CT) of the brain was normal. The headache settled with analgesia. A diagnosis of probable tension-type headache, with underlying active EORA, was made. One month later, he presented to an ophthalmologist with recurrence of headache associated with visual disturbance and was diagnosed with giant cell arteritis (GCA). Both CRP (77mg/L) and ESR (85mm/hour) remained raised. Neither temporal artery biopsy nor temporal artery ultrasound were possible due to the coronavirus disease 2019 (COVID-19) pandemic. The headache and visual symptoms resolved completely a week after prednisolone 60mg daily was prescribed. In parallel, the CRP dropped to 2mg/L and ESR 16mm/hour. The patient's glucocorticoid dose was then tapered. While on prednisolone 20mg daily, about 3 weeks later, he developed slurred speech and generalized weakness. Examination showed cerebellar signs and MRI brain showed acute cerebellar infarct. He was treated pragmatically as an atherosclerotic stroke with clopidogrel, and the steroid was rapidly tapered in view of absence of headache and normalization of infammatory markers. Four weeks later, he was noted to have persistent confusion and unsteadiness of gait. CRP was elevated at 92mg/L. An urgent positron emission tomography-CT (PET-CT) scan showed infammation in the vertebral arteries [Figure 1] and cerebellar stroke. Prednisolone 40mg daily was restarted which led to a rapid improvement in his symptoms and normalization of infammatory markers. The glucocorticoids were tapered in a slower manner this time. A diagnosis of GCA-related cerebellar stroke with vertebral vasculitis was made and, with glucocorticoids, the patient made a good clinical recovery. His infam-matory joints pain also improved in parallel. Conclusion: Stroke or transient ischemic stroke are rare complications, reported in 2.8-16% of patients with active GCA. Most studies report strokes as occurring between the onset of GCA symptoms and 4 weeks after commencement of glucocorticoids1-3. Vertebrobasilar territory is involved in 60-88% of cases of GCA-related stroke1-3. In contrast, the vertebrobasilar territory is affected only in 15-20% of atherosclerotic strokes1,2. One study reported fatal outcomes in 11 out of 40 patients (28%) with GCA-related stroke, 7 within 2-13 days of stroke2. To conclude, this case demonstrates that high-dose glucocorticoids with slower tapering were able to control GCA-related stroke due to vertebral vasculitis in patient with EORA on background methotrexate and sulfasalazine.

Audit of temporal artery biopsies for giant cell arteritis performed at the new Royal Adelaide Hospital over a three year period

Background: Giant cell arteritis (GCA) is a sight-threatening disease requiring long-term immunosuppression, which carries inherent risk. Temporal artery biopsy (TAB) is the gold-standard investigation to confirm the diagnosis. Guidelines classically recommend a post-fixation sample length of 20 mm to achieve reliable histopathological results, but recent studies suggest sample lengths >6 mm are adequate. Benchmarking/Standard: Various papers report a minimum TAB length ranging from >6 mm to >20 mm to avoid false negative histology results. No reports examine the effect of COVID lockdowns on GCA presentations and TABs. Methods: All TABs in South Australia processed by the public state-wide pathology provider from September 2017 until June 2020. Histological diagnosis and sample lengths were extracted from reports. Clinical information and biochemistry for cases at the Royal Adelaide Hospital were derived from medical records. Results: A total of 362 temporal artery biopsies were conducted;156 conducted at Royal Adelaide Hospital, of which 41% were performed by Ophthalmology. Thirty-one percent of Ophthalmology TABs were <10 mm compared to 20% outside Ophthalmology (p = 0.018). TABs performed by Ophthalmology were twice as likely to be positive (34.4% vs 17.2%). Visual symptoms (p = 0.046), older age (p = 0.02), elevated ESR (p = 0.002) and elevated platelets (p = 0.003) were significant predictors of positive histology. Length was not significantly associated with positive histology after adjusting for above factors (p = 0.617). COVID-19 precautions and lockdown in April-May 2020 did not significantly alter the number of TABs. Recommendations: Given that most TABs were performed by Ophthalmology registrars, more direct supervision and techniques such as ultrasound marking may increase sample length. However, TAB lengths <20 mm are acceptable.