Mean Prednisolone Dose Research Articles

Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy.

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24-102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68-0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Efficacy and safety of an early response-based tapering regimen of tocilizumab in children with systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.

Rituximab treatment for refractory and moderate-to-severe pemphigus patients in the pandemic era: A single-center retrospective study

Abstract Background: The management of refractory pemphigus in the pandemic conditions is challenging. There are limited data comparing the safety of rituximab and other immunosuppressive therapies during the COVID-19 pandemic. Objectives: We evaluated the safety and efficacy of rituximab and conventional treatments in patients with pemphigus who received treatment during the COVID-19 pandemic period. Methods: The patients with pemphigus treated with immunosuppressive treatments in a university hospital between September 2020 and May 2023 were retrospectively evaluated. All patients initially received conventional treatments. Fifteen of them who were refractory to prior treatments or could not use prednisolone due to adverse effects received rituximab. Eighteen patients were treated with only conventional treatments. Results: Thirty-three patients with a mean age of 50 ± 15 years were included in the study. Twenty-two of the patients (66.7%) were female. The baseline mean pemphigus disease area index (PDAI) score of the patients was 37 ± 34 (range: 4–168). The mean follow-up time was 13.8 ± 6.8 months. The mean PDAI scores were significantly lower after treatment in both rituximab and conventional treatment groups (P: 0.001, P &lt; 0.001; respectively). In the rituximab group, the monthly mean prednisolone dose was statistically reduced after rituximab treatment compared to before treatment (P &lt; 0.001). There was no statistically significant difference in the relative odds of COVID-19 positivity or death between the groups (3.06 (95% [confidence interval (CI): 0.68–13.79]; 0.57 [95% CI: 0.05–7.00], respectively). Of 11 patients diagnosed with COVID-19, one patient (1/7, 14.3%) in the rituximab group and two patients (2/4, 50%) in the conventional treatment group died from SARS-CoV-2. Conclusion: We observed that rituximab treatment was effective and safe for treatment-resistant moderate-to-severe pemphigus patients during the COVID-19 pandemic.

The role of infliximab in treating refractory cardiac sarcoidosis

Abstract Introduction Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents. Purpose To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis. Methods We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded. Results Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan. Conclusion This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.

Severe COVID-19 with persistent respiratory failure-A retrospective cohort study in a tertiary centre in Malaysia.

Management of severe COVID-19 patients with persistent respiratory failure after acute phase treatment is not only challenging, but evidence for treatment is scarce, despite some authors reporting favourable clinical responses to corticosteroid therapy in histologically proven secondary organising pneumonia (OP). This study aimed to report the course of the disease, radiological pattern and clinical outcomes of severe COVID-19 patients with persistent respiratory failure. This was a retrospective cohort study of severe COVID-19 patients who were admitted to a single tertiary centre from 1 January 2021 to 30 June 2021. The clinical data of the patients during admission and clinic follow-up, including radiological images, were traced using electronic medical records. In our cohort, the mortality rate for those with severe COVID-19 was 23.1% (173/749). Among the survivors, 46.2% (266/576) had persistent respiratory failure (PRF) after 14 days of illness. Of them, 70.3% (187/266) were followed up, and 68% (128/187) received oral corticosteroid (prednisolone) maintenance treatment. OP pattern made up the majority (81%) of the radiological pattern with a mean severity CT score of 10 (SD±3). The mean prednisolone dose was 0.68mg/kg/day with a mean treatment duration of 47 days (SD±18). About one-third of patients (67/187) had respiratory symptoms at 4 weeks (SD±3). Among 78.1% (146/187) who had a repeated CXR during follow-up, only 12 patients (8.2%, SD±3) had radiological improvement of less than 50% at 6 weeks (SD±3), with 2 of them later diagnosed as pulmonary tuberculosis. Functional assessments, such as the 6-minute walk test and the spirometry, were only performed in 52.4% and 15.5% of the patients, respectively. Almost half of the patients with severe COVID-19 had PRF, with a predominant radiological OP pattern. More than two-thirds of the PRF patients required prolonged oral corticosteroid treatment. Familiarising clinicians with the disease course, radiological patterns, and potential outcomes of this group of patients may better equip them to manage their patients.

Abstract 14627: Angiotensin-Neprilysin Inhibition in Cardiac Sarcoidosis

Introduction: Sacubitril/Valsartan is an established treatment for heart failure patients with reduced ejection fraction (HFrEF). However, there is a paucity of data on its use in patients with cardiac sarcoidosis (CS). Hypothesis To establish the beneficial role of Sacubitril/Valsartan in cardiac sarcoidosis. Methods All consecutive CS patients taking Sacubitril/Valsartan were identified from our database from 2016 to 2022. They were followed up for at least 6 months with serial echocardiography. Data regarding symptoms and echocardiographic parameters were compared using Wilcoxon signed rank test. Results A total of 30 CS patients taking Sacubitril/Valsartan were identified (mean age: 56.73±11.63 years old). The diagnosis of CS was determined in all patients by a multi-disciplinary team. Patients were male predominant (73.3%). The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 20%, 10%, 10% and 3.3% respectively. Beta-blockers, mineralocorticoid receptor antagonists, prednisolone, implantable cardioverter defibrillator and cardiac resynchronisation therapy (defibrillator) were present in 93.3%, 96.7%, 53.3%, 16.7% and 56.7% patients respectively. At the time of diagnosis, 24 (80%) patients were found to have active cardiac sarcoidosis on cardiac PET. At 6-months following the commencement of Sacubitril/Valsartan, there was a significant improvement in LV ejection fraction (38.77±10.26% vs 32.87±9.30%, p&lt;0.001), LV end-systolic diameter (4.89±1.06cm vs 5.14±1.07cm, p=0.013) and New York Heart Association class (1.6±0.55 vs 2.0±0.52, p=0.001). During the median follow up of 24.9 months, the composite end-point of death and cardiac transplantation was reached in 3 (10%) patients (3 deaths and 0 cardiac transplantation). The patients experiencing at least one sustained ventricular arrhythmia (or aborted sudden cardiac death) decreased from 9 to 7 (p=0.21), the mean prednisolone dose was also comparable (11.56±4.42 vs 10.28±3.71, p=0.50) and none of the patients stopped Sacubitril/Valsartan. Conclusions Sacubitril/Valsartan in cardiac sarcoidosis patients with HFrEF is associated with at least short-term improvements in LV remodelling and functional status.

Concomitant septic arthritis of the hip joint and femoral head avascular necrosis in patients with recent COVID-19 infection: a cautionary report

PurposeAt present, concomitant avascular necrosis (AVN) of femoral head and septic arthritis (SA) as a sequel of COVID-19 infection has yet not been documented. By large-scale use of life-saving corticosteroids (CS) in COVID-19 cases, our aim is to warn of the occurrence of hip joint infection in these patients.MethodsWe report a series of five cases in which patients developed septic arthritis concomitant with AVN after being treated for COVID-19 infection. The mean dose of prednisolone used in these cases was 1695.2 mg. The time period of onset of hip symptoms in our cases from the beginning of the COVID-19 infection was 56 days in the first case, 43 days in the second case, 30 days in the third case, 29 days in the fourth case and 50 days in the last case, with an average time of 41.6 days. All patients underwent surgery depending on the extent of articular cartilage damage by direct anterior approach.ResultsClinical and laboratory symptoms improved significantly in all patients. The mean visual analogue pain score of the patients decreased from 9.4 (9–10) before surgery to 2.8 (1–4) after 1 week of operation.ConclusionIn any patient with the history of COVID-19 infection specially those who have been treated with corticosteroid as one of the medications prescribed during the disease, any joint symptom specially in the hips should draw our attention to the joint infection, and with timely diagnosis and surgery, their hip joint can be saved.

Effects of anti-TNF biologic drugs on uveitis severity in Behçet patients: systematic review and Meta-analysis.

To investigate effects of anti-TNF biologic drugs on uveitis severity (comparing visual acuity logMAR levels) in Behçet patients. Three databases PubMed, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behçet's disease (BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted. The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis (with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies (28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity logMAR levels (MD=-1.5 IU/L, 95%CI: -2.1, -0.01). Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values.

OA42 Evaluating the effects on a clinical service of introducing ultrasound for diagnosis of giant cell arteritis using Lean methodology

Abstract Background/Aims In our trust, patients with suspected giant cell arteritis (GCA) were promptly started on high-dose prednisolone. However, until 2019, patients were waiting on average 28.5 days (median) for confirmation of diagnostic decision, which was mostly due to the time taken for temporal artery biopsy (TAB) to be performed and reported. We have made two major changes to our pathway: firstly (Jan 2019) adding temporal artery ultrasound (TAUS), and secondly (Mar 2020), routing GP referrals through our Primary Care Access Line (PCAL) to an allocated rheumatology registrar based at the same site as the TAUS. We used Lean methodology to pre-specify metrics to evaluate our pathway. Aim and Purpose: To assess changes over time across our five prespecified domains: delivery, quality, service, morale and cost. Methods We defined lead time as median time between entry to pathway and diagnostic confirmation. This was our delivery domain. We defined treatment for GCA as clinical diagnosis plus at least 6 months of treatment with “GCA-dose” steroids. Quality was measured for patients treated as GCA as the percentage with a positive confirmatory test; and for patients not treated as GCA as the cumulative prednisolone dose received for suspected GCA. Service and morale were assessed from patient and staff feedback, respectively. Cost was assessed via the patient-level costings team using standard NHS tariffs. We plotted a run chart by month and significant shift in delivery or quality was defined as six consecutive monthly values below the baseline median. Results TAUS was performed a median of 2.5 days from referral. Agreement between TAB and TAUS results was good. The run chart showed a significant shift in our delivery. Lead time fell from 28.7 days to 19.2 days after introduction of ultrasound, and further down to 7.7 days after the utilisation of PCAL. A significant shift was also seen in quality metrics. Proportion of GCA with positive TAB/TAUS increased from 29% to 56.3% following the introduction of TAUS, and further to 75% on the utilisation of PCAL. The total mean prednisolone dose for patient without GCA fell from 1.335g to 0.439g after introducing TAUS, and down to 0.139g after introduction of PCAL. Within costs, average per-patient costs of TAB/TAUS declined from £1004/patient to £718/patient to £378/patient. However, total GCA pathway referrals increased from 6/month to 10/month to 24/month, increasing overall costs. Staff and patient feedback (service, morale) were overall positive, but revealed the need for further improvements to manage the additional complexity and volume. Conclusion Lean methodology identified multiple metrics for evaluating the impact of TAUS and PCAL on our service. We have seen an improvement in delivery and quality. Measuring costs, morale and service helped identify unintended consequences and target further improvement. Disclosure T. Rajeswaran: None. A. Barr: None. V. Bassi: None. A. Chakrabarty: None. A. Cracknell: None. R. Darwood: None. S. Dass: None. S. Farrell: None. J. Hunter: None. T. Mitchell: None. J. Parvin: None. B. Sarker: None. I. Simmons: None. K. Sinclair: None. K. Smith: None. A. Sweeting: None. R. Tue: None. M. Troxler: None. R. Wakefield: None. S.L. Mackie: Consultancies; consultancy for Roche, Sanofi, AstraZeneca, Abbvie on behalf of her institution. Other; support from Roche to attend EULAR2019.

Low pre-pregnant body mass index is a risk factor for the decrease of postpartum bone mineral density in systemic lupus erythematosus patients received glucocorticoid therapy.

This study investigated postpartum bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) receiving long-term glucocorticoid (GC) therapy, assessed risk factors for decreased postpartum BMD, and evaluated change of BMD after postpartum initiation or restarting of osteoporosis drugs. We retrospectively examined 30 SLE patients who gave birth and 31 non-pregnant SLE patients. In the postpartum SLE patients, BMD was measured after delivery and 1year later. Multivariate analyses were performed to assess risk factors for decreased BMD in postpartum SLE patients. Patient age at pregnancy was 34.5 ± 4.5years, and SLE duration was 9.7 ± 6.0years. The mean prednisolone dose was 9.7 ± 3.2mg/day. Body mass index (BMI) was 21.6 ± 2.2kg/m2, with 13 women (43%) experiencing their first delivery. Postpartum BMD was 1.080 ± 0.120g/cm2 in the lumbar spine and 0.834 ± 0.109g/cm2 in the total hip. Bone loss occurred in six patients (21%) in the lumbar spine and 11 patients (37%) in the total hip. Postpartum lumbar spine BMD was significantly reduced compared to that in the non-pregnant group (1.143 ± 0.120g/cm2, p = 0.048). Multivariate analysis identified gestational age and low BMI before pregnancy as risk factors for hip bone loss. Postpartum BMD significantly decrease in SLE patients receiving long-term GC, and low BMI before pregnancy was a risk factor for the decrease. Preconception care to prevent osteoporosis and that regularly monitors BMD after delivery are needed.

Pemphigus patients with initial negative levels of anti-desmoglein: A subtype with different profile?

Pemphigus is a blistering autoimmune disease that is characterized by autoantibodies against desmogleins (Dsg), including anti-Dsg1 and anti-Dsg3. Despite the diagnosis of diseases, the anti-Dsg test by enzyme-linked immunosorbent assay (ELISA) is negative in a small group of pemphigus patients. The aim of this study was to evaluate the clinical course, clinical symptoms, and response to treatment in pemphigus patients with negative levels of anti-Dsg1 and anti-Dsg3. In this study, the data of pemphigus patients referred to Razi Hospital were retrospectively collected from the medical records from 2016 to 2020. Eight patients, whose initial anti-Dsg1/anti-Dsg3 was negative by the ELISA test, were enrolled and their clinical course, clinical signs, and response to treatment were evaluated. The mean age of the subjects (8 females) was 38.75 ± 12.09. The most common phenotype of the subjects was pemphigus vulgaris (PV) with mucosal involvement. Additionally, the common site of blister inception was mouth of the patients. The mean prednisolone dose received by the patients at the initiation was 32.5± 13.62 mg/day. According to Pemphigus disease area index (PDAI), six patients had mild severity, while two cases had moderate severity. Among the patients, six subjects received rituximab (RTX). Also, five patients experienced remission after 6.2± 5.21 months. PV is the most common phenotype of the disease and mucosal involvement is more common in patients with negative anti-Dsg-1/3 results. The severity of the lesions in most of the patients is mild at baseline and most patients seems to respond to RTX therapy and reach remission.

A multicenter, open-label, uncontrolled, single-arm phase 2 study of tirabrutinib, an oral Bruton’s tyrosine kinase inhibitor, in pemphigus

BackgroundThe treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton’s tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling. ObjectiveWe investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus. MethodsThis was a multicenter, open-label, single-arm phase 2 study of Japanese patients with refractory pemphigus receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent. ResultsIn total, 16 patients were evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 6.6 %–43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A relationship with tirabrutinib was ruled out for all serious AEs and Grade ≥3 AEs. ConclusionTreatment with tirabrutinib enabled remission and reduced oral corticosteroid exposure over time and did not result in any major safety concerns in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new treatment option for patients with refractory pemphigus.

P205 The contemporary presentation and management of giant cell arteritis with large vessel vasculitis

Abstract Background/Aims Giant cell arteritis with large vessel vasculitis (LV-GCA) represents a distinct, less researched sub-category of giant cell arteritis (GCA). In comparison to cranial GCA, the patient’s diagnostic pathway is less well described and it is thought that LV-GCA is underdiagnosed, including in patients with polymyalgia rheumatica and cranial-GCA. Advances in imaging (e.g. PET-CT) and treatment (tocilizumab), have provided additional options in the diagnosis and management of LV-GCA. The aim was to describe the contemporary clinical journey for patients diagnosed with LV-GCA. Methods The electronic patient health record system in NHS Lothian (TrakCare) was used to collect relevant data. Patients with imaging-confirmed large vessel vasculitis, diagnosed with GCA after 1 January 2017 were included. Follow-up was until August 2020. Results Eighteen patients with LV-GCA were included. The mean age was 65 years and 66.7% were female. Two patients had known cranial-GCA but 89% of patients were diagnosed exclusively with large vessel involvement. The most common symptoms were malaise (55%), weight loss (55%), polymyalgia rheumatica (55%) and limb claudication (44%). Pyrexia of unknown origin was a feature in only 17% of patients. Two patients were asymptomatic and were investigated on the basis of raised inflammatory markers. Mean CRP at baseline was 99mg/L and ESR 85mm/hour. The mean time from symptom-onset to diagnosis was 6.8 months (range 1 to 15 months). Sixteen patients (89%) were reviewed by at least one other secondary care specialist. One third of patients were referred from General Medicine followed by Vascular Surgery (16%) and General Practice (16%). 7/18 patients were inpatients at the time of referral. 56% of patients required two modalities of imaging to confirm large vessel involvement. The most commonly used imaging techniques (in descending order) were CT-Chest/Abdomen/Pelvis, CT-angiogram, PET-CT and Vascular Ultrasound. 50% of patients underwent follow-up imaging, most commonly MR- or CT-angiography. Mean follow-up was for 1.6 years. The mean prednisolone dose at 3 months (n = 18) was 24mg daily and 8mg at 12 months (n = 12). 28% of patients relapsed during the follow-up period at 4, 5, 8, 9 and 24 months post-diagnosis. 7/18 patients were commenced on methotrexate for steroid-side effects or for relapse. 8/18 received subcutaneous tocilizumab in combination with methotrexate in two cases. Three patients were started on azathioprine but only one continued. Conclusion In modern-day clinical practice, patients with LV-GCA experience a longer time to diagnosis than those with cranial symptoms. Patients with LV-GCA can experience an array of constitutional symptoms. Frequently, more than one imaging modality is required to confirm LV-GCA and the majority of patients will have seen other hospital specialists or have been admitted to hospital before diagnosis. Methotrexate and tocilizumab are the most frequently-used and effective steroid-adjunct in this single-centre cohort. Disclosure O. Cronin: None. N.D. McKay: Consultancies; Gilead. Other; Has received support for conference attendance from Pfizer and Gilead, Has received educational support from UCB, Gilead, Celgene, Biogen, Sanofi, Abbvie, Novartis, Pfizer. H. Preston: None. H. Harris: None. B. Hauser: None.

P210 Tocilizumab versus prednisolone only treatment for giant cell arteritis: an observational study

Abstract Background/Aims Giant cell arteritis (GCA) is a medical emergency that requires prolonged high dose glucocorticoids (GC). Tocilizumab (TCZ) is currently approved for GCA in combination with GC tapering for those at high risk of glucocorticoid toxicity, who relapse or have refractory disease. The aim is to evaluate indications and characteristics of patients who were started on TCZ and to assess the rate of relapse and steroid tapering for patients on TCZ compared with an age matched prednisolone (PDN) only treated control group (CTRL). Methods Retrospective review of electronic patient health record data of patients who were diagnosed and treated for GCA in a single rheumatology centre from January 2017- July 2020. All patients were initially treated with high dose PDN (40-60 mg/day) with subsequent steroid tapering with or without TCZ (162 mg/week). Results We included 36 GCA patients who were treated with TCZ+PDN and 26 patients with PDN only. Mean age of patients started on TCZ was 69.3±6.8, 81% were female. There was no significant demographic difference to the CTRL group.The most common reason for starting TCZ (50%) was a GCA relapse requiring uptitration of PDN. 13 patients (36%) started TCZ as they had developed significant steroid side effects including steroid-induced diabetes, hypertension and osteoporosis related fragility fractures. Almost one fifth of patients (19.4%) who were started on TCZ had imaging evidence of large vessel involvement.The mean PDN dose of patients who started TCZ was 26.6±13.1 mg/day. Patients who started TCZ were able to approximately half the PDN dose every 3 months. The average daily PDN dose was 11.3±7.0 mg after 3 months, 6.0±4.3 mg after 6 months, and 3.3±4.7 mg after 12 months of starting TCZ. When compared with the CTRL group (4%), significantly more TCZ patients (41.7%) were able to reduce the PDN dose to a low dose (0-5 mg) after 6 months treatment (p = 0.001).During the course of treatment more CTRL patients (34.6%) relapsed than patients receiving TCZ (11.1% vs CTRL, p = 0.013). The majority of TCZ patients (88.9%) stayed in remission and 2 (5.6%) patients completed 12 months treatment and have ceased therapy. 4 (11.1%) patients stopped Tocilizumab due to side effects (diarrhoea, diverticulitis, scalp irritation) and 2 stopped due to concerns over long term risks. Conclusion Our real-world study shows that TCZ is predominantly initiated in those who relapse or develop GC related side effects. Patients who received TCZ were able to half their PDN dose every 3 months and had lower 6 and 12-month PDN requirements compared to those on PDN solely. The relapse rate was significantly higher in the PDN only treated group than in the TCZ group. TCZ is a good option as steroid sparing agent for the treatment of GCA. Disclosure H. Preston: None. O. Cronin: None. B. Kuske: None. N.D. McKay: None. B. Hauser: Honoraria; Dr Hauser has received speaker fees from Roche.

Factors affecting the Apgar score of offsprings born to mothers suffering from systemic lupus erythematosus.

To reveal which disease activity parameters affect low Apgar scores of newborns, which is considered as a predictive parameter for neurological development.We examined retrospectively the data from 42 newborns who were delivered from systemic lupus erythematosus (SLE) mothers from 2006 to 2019. We evaluated whether the disease activity parameters, such as the achievement ratio of lupus low disease activity state (LLDAS), SLE disease activities index (SLEDAI), complement level, titer of anti-double stranded DNA (anti-dsDNA) antibody, therapeutic agents were related with low Apgar scores of newborns.In 42 newborns, adverse pregnancy outcomes, especially preterm birth (16.7%), low birth weight (31.0%) light-for-date (11.9%) were associated with disease activity parameters or prednisolone dose. Apgar scores at 1 minute were related with unachieved LLDAS and the titer of anti-dsDNA antibody at first and third trimester, SLEDAI score and complement level at third trimester, mean prednisolone dose. Apgar scores at 5 minutes were also associated with the titer of anti-dsDNA antibodies at first and third trimester and mean prednisolone dose. Multivariate analysis showed only high titer of anti-dsDNA antibody was significantly associated with low Apgar score at both one minute and 5 minutes.In our retrospective study, high titer of anti-dsDNA antibodies at first and third trimester was a risk factor for low Apgar scores of newborns born to SLE mothers. We considered that high titer of anti-dsDNA antibody influenced on childrens neurological development, therefore, there is a need for long-term follow-up study of SLE offsprings.

Stratified glucocorticoid monotherapy is safe and effective for most cases of giant cell arteritis.

ObjectivesHigh-dose glucocorticoids anchor standard care in GCA but are associated with significant toxicity. We aimed to evaluate the safety and effectiveness of a stratified approach to glucocorticoid tapering. The strategy aggressively reduced glucocorticoid doses in those manifesting an adequate early response to treatment, with a view to minimizing glucocorticoid complications.MethodsA retrospective, population-based study of GCA was performed. All cases were confirmed by temporal artery biopsy between November 2010 and November 2015. Baseline and outcome data were extracted from secondary and primary care records at diagnosis and 1 year follow-up. The primary outcome was loss of vision. Secondary outcomes included remission and relapse rates and CS-related complications.ResultsThe cohort consisted of 73 patients (76% female; mean age 73.5 years, s.d. 7.6 years). At presentation, a reduction in visual acuity was recorded in 17 patients (22.3%). The median CRP at diagnosis was 69.5 mg/l [interquartile range (IQR) 40.5–101 mg/l], with a median ESR of 80 mm/h (IQR 60–91 mm/h). At 1 year, remission was achieved in 64 patients (87.7%), whereas 10 patients (13.7%) relapsed. A single patient sustained visual loss after initiation of therapy. The median CRP at 1 year was 4 mg/l (IQR 4–9.5 mg/l) and the mean prednisolone dose was 5.4 mg (0–15 mg). CS-related complications were observed in 10 patients (13.7%).ConclusionA stratified approach to CS tapering appeared safe and effective in GCA. It was associated with a high rate of remission and promisingly low rates of relapse at 1 year follow-up. These real-world data indicate that glucocorticoid exposure can be minimized safely in some patients with GCA.

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach.

Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA. We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided. Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises. Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.

Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study.

Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5-3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9-8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01-1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02-1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0-5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03-1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03-1·23], p=0·0144), and age at enrolment (1·04 [1·01-1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43-2·06], p=0·8675). Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

Tacrolimus for ulcerative colitis in children: a multicenter survey in Japan.

Background/AimsTacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis. MethodsWe retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged < 17 years treated with tacrolimus between 2000 and 2012. Patients’ characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score < 10; treatment response was defined as a PUCAI score reduction of ≥ 20 points compared with baseline. ResultsPatients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11–15] years). Thirty-nine patients were steroid-dependent and 26 were steroidrefractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05–0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P< 0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy. ConclusionsTacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children.

Effect of rituximab on the manifestations of activity and pulmonary function in patients with systemic sclerosis: one-year follow-up evaluation

The choice of drugs for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SS) is currently very limited. Data from a number of studies show that rituximab (RTM) can improve lung function and reduce the severity of skin fibrosis in patients with SS.Objective: to evaluate the efficiency of RTM in a cohort of patients with SS-associated ILD after one-year follow-up. The indications for prescribing RTM were: 1) the inefficiency of standard therapy with glucocorticoids and immunosuppressants (ISs) or the impossibility of their use; 2) the early stage (first 3 years of the disease) with signs of poor prognosis, such as diffuse form, high skin scores (&gt;14), male gender, rapid progression with a significant initial decline in forced vital capacity (FVC) and/or diffusion lung capacity (DLC), and a high anti-Scl-70 antibody positivity.Subjects and methods. The investigators selected a group of patients who had at least two assessment points at a 12-to-18 month interval (the mean follow-up period of 13±2 months) and took at least 1 g of RTM during this period. The investigation included 71 patients with a valid diagnosis of SS. Multi-slice spiral computed tomography (MSCT) revealed ILD in 90% of patients. The disease duration was 5.6±4.4 years. The presence of anti-Scl-70 antibodies was detected in 73% of patients. The mean cumulative dose of RTM was 1.43±0.6 g; 48 patients in Group 1 received ≤2 g of RTM (the mean dose, 1.1±0.1 g) and 23 patients in Group 2 took ≥2 g of RTM (mean dose, 2±0.6 g). Before starting treatment with RTM, all the patients received concomitant therapy with prednisone and 45% - with immunosuppressants.Results and discussion. The results assessed by a physician showed that good and moderate effects of the therapy were observed in 52 (73.2%) and 16 (22.6%) patients, respectively; no effect was seen in 3 (4.2%) patients. Overall, 95.8% of patients reported various degrees of improvement. There were significant changes as reductions in the disease activity index, skin scores, C-reactive protein and IgG levels, the number of patients with a high antinuclear antibody level, and the mean dose of prednisolone as well as increases in an oral aperture size, left ventricular ejection fraction, and 6-minute walk test scores. There were no changes in pulmonary artery systolic pressure and the HAQ DI. FVC increased from 77.35±19.9 to 82.6±20.7% (p=0.001). A minimal clinically significant increase in FVC ≥5% was noted in 41 (57.7%) people. The overall improvement in FVC (ΔFVC) reached 5.24%, while the changes were more significant in Group 2 (ΔFVC 8.98%) than in Group 1 (ΔFVC 3.75%; p=0.01). DLC remained stable, but there were significant group differences: ΔDLC was 3.75% in Group 2 and, conversely, decreased in Group 1 (1.6%; p=0005). The safety profile of the therapy was regarded as good and quite comparable with both the safety profile of ISs and the use of RTM in other trials. Infectious complications were recorded to be most common in 11 (15%) people. Of these, upper respiratory tract infections developed in 7 patients; plantar phlegmon occurred in one case; urinary tract infection and herpes zoster were detected in two and one cases, respectively.The results of this study confirm data from other studies that have demonstrated that RTM exerts a positive effect on SS-associated ILD. We were the first to show the association of positive changes in the measures of pulmonary function tests with the dose of RTM.