Doses Of Oral Glucocorticoids Research Articles

7038 Continuous Subcutaneous Hydrocortisone Infusion Is Practical And Effective In Select Patients With Adrenal Insufficiency

Abstract Disclosure: J.E. Lee: None. O. Hamidi: None. S. Mirfakhraee: None. Continuous subcutaneous hydrocortisone infusion (CSHI) via insulin pump is an alternative therapy for treating patients with adrenal insufficiency (AI) and allows for adjustable hydrocortisone delivery to provide more physiologic glucocorticoid replacement. Retrospective case series of 9 patients on CSHI showed a reduction in total daily dose of glucocorticoid by 34% and a decrease in hospitalization admissions due to adrenal crisis by 50%. In a double-blind placebo-controlled study, CSHI in patients with primary AI did not demonstrate benefit in subjective health status metrics compared to oral hydrocortisone; however, patients had good baseline subjective health scores. Due to a scarcity of data, CSHI is likely underutilized in patients who may benefit from this individualized therapy. Our research objectives were to analyze the change in total daily glucocorticoid dose, number of adrenal crises events and hospitalization days, glucocorticoid-related comorbidities, and quality of life of patients transitioned to CSHI. We performed a single-center, retrospective longitudinal follow-up study in 23 consecutive patients (87% women, median age 40 years at time of CSHI initiation) treated with CSHI between 2015 and 2023. Types of adrenal insufficiency were 48% secondary AI, 35% glucocorticoid induced AI, and 17% primary AI. CSHI delivery settings were generated by a formula that we derived using each patient’s daily oral glucocorticoid dose and preferred waking time. Median time from AI diagnosis to CSHI implementation was 41 months, and median duration of CSHI was 25 months. Total daily dose of glucocorticoid (in hydrocortisone equivalent) before CSHI vs during CSHI decreased from 30.0mg (15.0mg to 80.0mg) to 26.6mg (14.4mg to 200.5mg) (p= 0.45). Median number of adrenal crisis events decreased from 1 (0 to 13) to 0 (0 to 38) (p=0.25), and hospitalization days due to adrenal crisis decreased from 2 (0 to 46) to 0 (0 to 58) (p=0.53). No significant differences were noted for change in weight, blood pressure, diabetes, cardiovascular and cerebrovascular events, total cholesterol, LDL, and triglyceride levels. Median HDL decreased from 59 to 51 (p=0.01). In terms of subjective health status, 10 patients completed SF-36 survey while on CSHI. Significant impairments were noted in physical health, vitality, and general health with median score less than 40. At the conclusion of the study, 20 patients (87%) preferred CSHI therapy. Only 3 patients stopped CSHI for reasons of inconvenience, skin irritation at pump site, and better symptom control on oral therapy. No significant CSHI-related safety concerns were noted. In conclusion, CSHI is a safe and effective way to deliver individualized therapy to patients with difficult to control AI. CSHI led to reduction in glucocorticoid exposure and fewer adrenal crisis events and hospitalization days due to adrenal crisis. Presentation: 6/1/2024

Use of Glucocorticoids in SLE: A Clinical Approach.

Glucocorticoids (GCs) are one of the most effective first-line treatments for systemic lupus erythematosus (SLE). However, GC burden is associated with damage. The initial GC dose and tapering schedule should be tailored to the severity of the clinical scenario. As lupus therapy should prompt remission while minimising damage, recent guidelines recommend a more accurate approach to the use of GCs, setting lower starting doses and rapid tapering schemes, and encouraging maintenance prednisolone doses <5 mg/day. Methylprednisolone pulses (MP) help to reduce the dose of oral GCs and improve the clinical response in both severe and non-severe manifestations, without significant side effects. Fixed-tapering GC scheme provides a useful strategy to reduce GCs exposure. Long-term antimalarial treatment and early initiation of immunosuppressive drugs improve clinical efficacy while reducing GC toxicity. Besides, withdrawal of GCs is an achievable goal in patients in prolonged remission on stable treatment, and recent studies have attempted to identify the most suitable candidates. In this article, we review the pharmacological basis, clinical evidence of efficacy, dose-related harms, and potential withdrawal of GCs. We also review guidelines recommendations and finally give a personal and practical approach to dealing with the use of GCs in SLE patients.

Glucocorticoid toxicity index in patients with systemic lupus erythematosus (preliminary data)

Objective: to investigate the contribution of glucocorticoids (GC) to the development of irreversible organ damage in patients with systemic lupus erythematosus (SLE) using the GC toxicity index (GTI).Material and methods. The study included 65 patients with SLE who met the 2012 SLICC classification criteria. GTI, disease activity according to the SLEDAI-2K index and the SLICC damage index (DI) were determined in all patients, and standard laboratory and immunological tests were performed.Results and discussion. Patients were predominantly female (n=56, 86%), median disease duration was 76 [2; 288] months, SLEDAI-2K – 8.8 [0; 26], DI SLICC – 1.0 [0; 5], DI SLICC &gt;0 was found in 28 (43%) patients. The median duration of GC therapy during the disease period was 66.0 [0; 288] months, maximum dose of GC – 32.7 [0; 80] mg, median of total GC dose during intravenous administration was 2942 [0; 17 812.5] mg, GTI at the time of enrolment in the study – 19 [0; 37] points. GTI &gt;0 was present in 47 (72%) of 65 patients. GTI correlated with disease duration (r=0.33; p&lt;0.008); maximum dose of oral GCs (r=0.31; p&gt;&lt;0.012); duration of GC use (r=0.35; p&gt;&lt;0.005); DI SLICC (r=-0.43; p&gt;&lt;0.0001). In patients with an average disease duration of more than 3 years, GTI&gt;˂0.008); maximum dose of oral GCs (r=0.31; p˂0.012); duration of GC use (r=0.35; p˂0.005); DI SLICC (r=-0.43; p˂0.0001). In patients with an average disease duration of more than 3 years, GTI was significantly higher than in patients with a disease duration of 1–3 years (p=0.023).Conclusion. An GTI&gt;0 was found in 72% of SLE patients, which increased significantly with disease duration. The GTI value was influenced by the duration of SLE, the duration of GC treatment and the maximum GC dose during the disease period. A statistically significant correlation was found between the GTI and the SLICC DI, allowing the GTI value to be used as an additional component in the assessment of the contribution of GCs to the development of irreversible organ damage in patients with SLE. It is recommended that GTI is assessed in all patients with SLE receiving long-term GC treatment for the purpose of dose adjustment.

An odd case of immune-mediated necrotizing myopathy, complicated with sagittal, transverse and sigmoid sinus thrombosis

INTRODUCTION: Immune-mediated necrotizing myopathy (IMNM) is a rare variant of immune-mediated inflammatory myopathy (IMIM) that exhibits a severe prognosis and is unresponsive to conventional treatment. (1,2)Notably, the incidence of immune-mediated inflammatory myopathies (IMIMs) is low, estimated at 1.16 to 19/million/year and only 3-6% of IMIMs are diagnosed as IMNM. (1,3–5). Systemic inflammation has been found to play a crucial role in promoting the onset of cerebral venous thrombosis. (6,7) MATERIAL AND METHODS: We present the case of a 46-years-old Chinese woman, without any known prior pathology, who was referred to the Rheumatology Department for symmetrical, proximal muscle weakness of the limbs, dysphagia for solid food, and weight loss (5 kg within 2 months). The pathologic clinical examination revealed itchy erythematous plaques on the posterior thoracolumbar region and signs of muscle weakness. Laboratory workup showed significant inflammatory syndrome, severe muscle and hepatic cytolysis syndrome, and positivity for thyroid-specific autoantibodies but with normal thyroid function, positivity for antinuclear antibodies (more precisely: SS-A, Ro-52, SS-B), and myositis antibodies (SRP, Ro-52, SAE1, PM-Scl, MDA5). The CT scan of the thoracic, abdominal, and pelvis showed fibrosis of the lungs, hepatic hypertrophy, and an enlarged uterus, further diagnosed by transvaginal ultrasound as adenomyosis. The positive diagnosis is immune-mediated necrotizing myopathy. Differential diagnoses included dermatomyositis, toxic/infectious myositis, hypothyroidism, and neuro-muscular diseases (5,8). The initial treatment was made with glucocorticoids (pulse therapy followed by oral therapy) and immunosuppressants (Mycophenolate Mofetil – stopped because of severe dyspepsia and myelosuppression). After five days of pulse therapy, the patient developed muscle weakness and paresthesia on the left side of the body, and the cerebral CT scan revealed sagittal, transverse, and sigmoid sinus thrombosis. Thrombophilia screening uncovered the positivity of the lupus anticoagulant. (9) RESULTS: The patient was treated with anticoagulants (low molecular weight heparin, and afterward Vitamin K antagonist), low doses of oral glucocorticoids, and immunosuppressant (Methotrexate), without any other adverse event. CONCLUSION: In the presence of the lupus anticoagulant, even though the antiphospholipid syndrome is not confirmed, the only anticoagulant therapy that has proven its efficacy is the Vitamin K antagonist. Immune inflammatory myopathies, like IMNMs, create a significant inflammatory status that leads to hypercoagulability and endothelial injury, which exposes collagen and tissue factors, promoting further platelet aggregation, and can even lead to cerebral thrombosis. (2,6)

Effectiveness of early glucocorticoids in myasthenia gravis: a retrospective cohort study.

This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group. Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05). Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.

Portrait of a patient with systemic lupus erythematosus for the prescription of the type I interferon inhibitor anifrolumab

In recent years the use of monoclonal antibodies that block activity of type I interferon (IFN) or its receptors has become the new approach in the pharmacotherapy of systemic lupus erythematosus (SLE).Objective: to characterize patients with SLE treated with the type I IFN receptor inhibitor anifrolumab (AFM, Saphnelo®).Material and methods. The prospective 12-month study included 21 patients with SLE who met the 2012 SLICC criteria. Standard laboratory and immunological markers for SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE and the CLASI index was used to determine the severity of the mucocutaneous syndrome. Organ damage was assessed using the SLICC/ACR Damage Index (DI). The LupusQol and FACIT-Fatigue questionnaires were used to analyze health-related quality of life (HRQoL).Results and discussion. Female patients prevailed in the study, female/male ratio – 17 (81%)/4 (19%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. The majority of patients (86%) had moderate or high disease activity according to the SLEDAI-2K index. Among the clinical manifestations of SLE, skin and mucous membranes lesions predominated (81%). Non-erosive polyarthritis of varying severity was observed in 66% of cases. Serositis showed 24% of patients (pleurisy, pericarditis), 43% had hematological abnormalities (hemolytic anemia, leukopenia, lymphopenia) and 14% - urinary syndrome (daily proteinuria up to 0.5 g/l and/or urinary sediment – leukocytes/erythrocytes/cylinders up to 5 in the field of view in the absence of urinary tract infection). All patients had immunological disorders. 14% of them were diagnosed with antiphospholipid syndrome (APS) and 43% with Sjögren's syndrome.All patients received hydroxychloroquine, 95% received glucocorticoids (GC) from 5 to 60 mg/day, 66% received immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate). 33% of patients had anamnesis of treatment with biologic disease modifying antirheumatic drugs (rituximab, belimumab, dual anti-B-cell therapy) and Janus kinase inhibitor baricitinib. All patients experienced a significant deterioration in HRQoL.Conclusion. The indications for prescribing AFM to 21 patients with SLE were: active SLE according to SLEDAI-2K and/or CLASI with predominant involvement of skin, its appendages and development of polyarthritis with immunological disorders, intolerance/ineffectiveness of previous standard therapy and inability to achieve low average daily doses of oral GCs. Other clinical manifestations in some patients were: serositis, mild hematological disorders (Coombs-positive anemia, leukopenia), urinary syndrome. AFM could be prescribed for a combination of SLE with secondary APS and Sjögren's syndrome as well as for a high DI SLICC.

Persistence of Janus-kinase (JAK) inhibitors in rheumatoid arthritis: Australia wide study

BackgroundTo compare persistence of disease-modifying antirheumatic (DMARDs), with a focus on Janus kinase (JAK) inhibitors in Australian rheumatoid arthritis (RA) patients. MethodsA retrospective observational study was conducted among 4,521 RA patients (females n=3,181 [70.4%]), using data from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, aged ≥18 years and initiating a DMARD between 2011 to 2021. Kaplan-Meier analysis was used to estimate persistence rates, defined as occurrence of 6 months gap after the end of a drug dispensing. ResultsTwelve-month persistence rates were 72% for upadacitinib, 61% for baricitinib, 58% for subcutaneous tumor necrosis factor-alpha inhibitors (TNFi), 55% for tocilizumab, 53% for tofacitinib, and 49% for abatacept. Median treatment persistence was not reached for upadacitinib (n=574) and baricitinib (n=553); and was 15.0 months for tofacitinib (95% CI 13.5–19.5), 20.5 months for TNFi (95% CI 19.0–22.4), 19.1 months for tocilizumab (95% CI 17.9–23.6), and 12.5 months for abatacept (95% CI 10.4–14.9). Persistence rates on first-line JAK inhibitors were 68% for upadacitinib and baricitinib and 55% for tofacitinib, and 49% for TNFi, 55% for abatacept, and 57% for tocilizumab; rates were sustained for upadacitinib, TNFi, and tocilizumab but dropped to 59% for baricitinib and 47% for abatacept in the second-line treatment. For each b/tsDMARD, persistence rates were higher when combined with methotrexate or other conventional synthetic DMARDs. The median oral glucocorticoid dose decreased from 4.3 mg/day (range:0–40) to 2.3 mg/day (range:0–22) over 2 years. Changes were significant for all RA DMARDs, tofacitinib and baricitinib combined (1–2 years post initiation only), TNFi, abatacept, and tocilizumab. ConclusionsIn a real-world setting, we showed highest persistence rates on upadacitinib, followed by baricitinib and then TNFi therapy and was improved by co-therapy. All agents appeared to be corticosteroid sparing.

Long-term results of therapy with sequential use of rituximab and belimumab in patients with systemic lupus erythematosus

Objective: To evaluate the efficacy of combination therapy with rituximab (RTM) and belimumab (BLM) in patients with systemic lupus erythematosus (SLE) during long-term follow-up. Material and methods. Twelve patients with definite high- and moderate activity SLE were included in the study. Nine of them had skin and joint manifestations, and the others had renal, peripheral nervous system involvement, and vasculitis. Patients received RTM at a dose of 500–2000 mg with premedication with 6-methylprednisolone and then BLM according to the standard regimen of 10 mg/kg once a month. Patients were divided into two groups according to the timing of assessment of long-term outcomes. In the 1st group, data were evaluated after 7–9 years (n = 4), and in the 2nd group – after 2–4 years (n = 8) after the prescription of biologic disease-modifying antirheumatic drugs (bDMARDs). Efficacy and tolerability of therapy, SLE activity, and dose of oral glucocorticoids (GC) were evaluated. Results and discussion. Against the background of combination therapy, clinical and immunological response was achieved in 11 of 12 patients after one year (median SLEDAI-2K at baseline – 10 [9.5; 14.5] points, 6 and 12 months after administratrion of BLM – 4 [2; 6] points). When bDMARDs were prescribed in the first two years of the disease, patients responded better to therapy and showed more significant positive dynamics in clinical and laboratory parameters. Subsequently, BLM therapy was limited to an average of 2 years, during which a stable remission was achieved. Prescribing bDMARDs allowed GC to be used as initial therapy in an exacerbation of SLE in medium and low doses (subsequently further reduced). Clinical remission was achieved and maintained in 7 patients, exacerbation at different time points after discontinuation of bDMARDs occurred in 3 patients, efficacy waned in one patient, and no result was achieved with combination therapy in another patient. Conclusion. The most pronounced positive result can be expected when a bDMARDs are prescribed as early as possible after diagnosis of SLE (in the first 2 years of the disease). It is advisable to administer BLM infusions as recommended once a month without long breaks between injections for at least 2 years and to continue until a durable effect is achieved. The use of low-dose GC and its discontinuation is an achievable goal, but careful monitoring of patients is needed to detect early symptoms of exacerbation.

A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

An Integrated Approach in Management of Pemphigus Vulgaris

Pemphigus refers to a group of autoantibody-mediated intra-epidermal blistering diseases characterized by loss of cohesion between epidermal cells (a process termed acantholysis). Applying pressure to the skin of these patients may elicit the separation of the epidermis which is known as Nikolsky’s sign. Pemphigus vulgaris can be compared with Agnivisarpa based on similar manifestation. The mainstay of treatment is systemic glucocorticoids in allopathy science. The current mortality is around 5% with glucocorticoids treatment. Case History: This case report is of 40 years old male patient who presented with blisters formation on whole over body, perspiration, itching and burning since last 6 months. He was treated in indoor department with Snehana Cikitsa mainly along with oral glucocorticoids for 25 days. The dose of oral glucocorticoids was tapered with improvement in patient’s condition. Result: At the time discharge, patient was prescribed 10mg prednisolone and oral Ayurvedic medicines. After 25 days of treatment patient had more than 90% relief and glucorticoids was stopped. On the 2nd follow of treatment patient was kept only on Ayurvedic medicines. During first two follow-ups, patient had significant relief.

Treatment pattern and changes in oral glucocorticoid dose after tocilizumab treatment in patients with adult Still's disease: An analysis of a Japanese claims database.

Intravenous tocilizumab (TCZ-IV) was approved for the treatment of adult Still's disease (ASD) in Japan in May 2019 based on its efficacy and safety in a phase III randomized controlled trial. This study determined treatment patterns in patients with ASD and assessed oral glucocorticoid (GC) dose changes after TCZ-IV administration in Japanese clinical practice. Patients in the Medical Data Vision database aged 16 years or older with one or more of International Classification of Diseases, 10th revision codes M061 (ASD) or M082 (systemic juvenile idiopathic arthritis) during January 2017-March 2021 (cohort 1) and those initiating TCZ-IV during May 2019-March 2021 (cohort 2) were included. In cohort 1, the proportion of patients who were prescribed interleukin-6 inhibitors (mainly TCZ-IV) increased from 10.8% (January-April 2019 [before TCZ-IV approval]; n = 2002) to 18.3% (January-March 2021 [after TCZ-IV approval]; n = 2008). In cohort 2 (n = 193), 84.5% of patients were on oral GCs (≤5 mg/day: 23.8%) at index date (initial TCZ-IV prescription date); 46/70 (65.7%) were on oral GC at 5 mg/day or higher 12 months after TCZ-IV treatment (primary outcome). After 12 months of treatment, the TCZ-IV retention rate was 73.6% and the TCZ-IV administration interval was every 4 weeks and every 2 weeks in 31.9% and 27.7% of patients, respectively. The use of interleukin-6 inhibitors increased by 7.5% points in Japanese patients with ASD ~2 years after TCZ-IV approval, suggesting that an unmet medical need existed. This study suggests the potential GC-sparing effect of TCZ-IV in patients with ASD in clinical practice.

Treatment patterns in paediatric and adult patients with SLE: a retrospective claims database study in the USA

ObjectiveTo assess real-world treatment regimens and patterns in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) cohorts, including similarities in treatments, duration of use and adherence.MethodsThis retrospective study utilised data from...

#3047 A NEW ADJUNCTIVE THERAPY WITH AVACOPAN FOR ANCA-ASSOCIATED VASCULITIS

Abstract Background and Aims Glucocorticoids have been the standard treatment for anti-neutrophil cytoplasm autoantibody-associated vasculitis (AAV). Avacopan, a complement C5a receptor inhibitor, has been approved for the treatment of AAV in Japan, the USA, Germany, and Austria. The use of avacopan is supported by evidence from trials demonstrating disease remission with limited use of glucocorticoids [1–3]. Avacopan is a new, promising adjunctive agent for standard induction therapy for AAV and may potentially reduce steroid use. Method We assessed treatment responses of patients with AAV who did not require dialysis between 2018 and 2023. Group 1 consisted of six adult patients who were treated with avacopan (30 mg, twice daily) plus reduced-dose prednisone, and Group 2 consisted of 14 patients who received high-dose prednisone. We compared the mean dose of prednisone, Birmingham Vasculitis Activity Score (BVAS), creatinine, urine protein/creatinine ratio (UPCR), and C-reactive protein (CRP) at weeks 0 and 12 between the two groups. Results The mean total prednisone dose of oral glucocorticoids at both weeks 0 and 12 was much lower in Group 1 than in Group 2 (p&amp;lt;0.05). Mean BVAS, creatinine, UPCR, and CRP in Group 1 was comparable to Group 2. Steroid-related toxicity occurred in three of six (50%) patients in Group 1, and 5 of 14 (36%) patients in Group 2. Liver damage related to avacopan occurred in two of six (33%) patients in Group 1. Conclusion Herein, we describe practice observations on the use of avacopan in patients with AAV. While further studies are needed to confirm the efficacy of avacopan because the number of cases treated with avacopan is still lacking, our findings suggest that avacopan was beneficial in AAV patients because of the absence of steroid dependence.

Design of a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Participants with Active Idiopathic Inflammatory Myopathies (SPIREA) (P10-5.007)

Design of a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Participants with Active Idiopathic Inflammatory Myopathies (SPIREA) (P10-5.007)

P118 Baseline Characteristics of and Early Outcomes in the First 200 Patients With Rheumatoid arthritis Treated With Filgotinib in a Prospective Observational Study

Abstract Background/Aims Filgotinib (FIL) is a preferential Janus kinase 1 inhibitor, approved in Europe for the treatment of Rheumatoid arthritis (RA). A phase 4 European study of FIL (FILOSOPHY; NCT04871919) in patients with RA is ongoing. We report baseline characteristics and 1-month efficacy data from the first 200 patients. Methods The prospective, observational study will enroll approximately 1500 patients aged ≥18 years with moderate-severe active RA, prescribed FIL for the first time in accordance with the product label. We report baseline demographics, disease characteristics, comorbidities, prior treatments, reasons for starting FIL, and mean change from baseline (CFB) in pain severity (measured using a 10-cm visual analog scale [VAS]) and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score (range 0-52) via electronic PRO data collection at Week 1 and Month 1, and mean CFB in Clinical Disease Activity Index (CDAI; range 0-76) score at Month 1. The proportion of patients with clinically meaningful CFB in FACIT-fatigue (increase of ≥ 4) and VAS pain (reduction of ≥ 10) from Week 1 to Month 1 was reported. Patients included in analysis were enrolled May 2021-February 2022. Results 206 patients were enrolled from Germany (n = 134), UK (n = 40), Netherlands (n = 27), Belgium (n = 4), and Italy (n = 1); nearly 75% were female, mean (standard deviation [SD]) age 56.8 (10.6) years, and mean (SD) RA duration 10.0 (9.5) years. Approximately 40% of treated patients had comorbidities, most common: hypertension (28.3%), dyslipidemia (9.1%), type 2 diabetes mellitus (5.3%). FIL was started due to inadequate response (43.3%), loss of response (40.6%), or intolerance (non-allergic) to previous treatment (5.9%), or for other reasons (10.2%). Of treated patients, 167 (89.3%) received FIL 200 mg and 20 (10.7%) received FIL 100 mg (study drug information was pending for 19 patients). FIL monotherapy was taken by 55.6% of patients (19.3% with glucocorticoids), while 37.4% received FIL in combination with MTX (13.4% with glucocorticoids). Mean (SD) and median (range) daily dose of oral glucocorticoids at baseline was 7.5 (6.0) mg and 5.0 (1.0-30.0) mg. At Week 1 and Month 1, respectively, mean (SD) CFB in FACIT-fatigue score was 3.7 (6.9) and 6.8 (8.6), and mean (SD) CFB in VAS pain score was -11.9 (18.0) and -22.2 (27.8). At Month 1, mean (SD) CFB in CDAI score was -13.7 (17.1). Conclusion These are the first international real-world data to be reported from a cohort of RA patients treated with FIL. At baseline, patients generally had moderate disease activity. Initial interim data indicate rapid improvements in disease measures with FIL treatment (given as combination therapy or monotherapy, with/without glucocorticoids), which could be observed as early as Week 1 for VAS pain and FACIT-fatigue scores. Long-term follow-up is needed to further evaluate effectiveness and safety. Disclosure J. Galloway: Other; AbbVie, AstraZeneca, Biogen, Celgene, Galapagos, Gilead, Janssen, Medicago, Lilly, Novartis, Novavax, Pfizer, Roche, UCB. K. Bevers: None. P. Verschueren: Other; AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Roularta, Sidekick Health. R. Caporali: Other; AbbVie, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Pfizer, Roche, UCB, Eli Lilly, Gilead, Sanofi. S. Romero Yuste: Other; Pfizer, Lilly, AbbVie, Biogen, Sanofi. J. Avouac: Other; Galapagos, AbbVie, Lilly, Pfizer, Bristol Myers Squibb, Novartis, Fresenius-Kabi, Sanofi, Sandoz, Nordic Pharma, Biogen, Medac, Janssen, Roche-Chugai. E. Gvozdenovic: Other; Galapagos. K. Harris: Other; Galapagos. M. Zignani: Other; Galapagos. G. Burmester: Other; AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc.

Glucocorticoid exposure and the risk of serious infections in rheumatoid arthritis: a marginal structural model application.

Observational studies have reported an increased risk of infections associated with glucocorticoids in RA, not supported by evidence from randomized controlled trials. Inappropriately accommodating time-varying exposure and confounding in observational studies might explain the conflicting results. Therefore, we compared the incidence of serious infections between different oral glucocorticoid dose patterns over three years in a prospective inception cohort, adjusting for time-varying confounders in marginal structural models. We included 9654 newly diagnosed RA patients from the Swedish Rheumatology Quality Register between 2007-2018 and followed them for three years after the first rheumatology visit. Follow-up was divided into 90-day periods. A mean oral prednisone daily dose was calculated for each period and categorized into 'no use', 'low' (≤10mg/day) and 'high' (>10mg/day) doses. The incidence of serious infections (hospitalization for infection) over follow-up periods was modelled by pooled logistic regression allowing separate effects for recent and past exposure. An increased incidence of serious infections was associated with higher compared with lower doses and with more recent compared with past glucocorticoid exposure. Over 3 years of follow-up, the marginal structural models predicted one additional serious infection for every 83 individuals treated with low GC doses for the first 6 months, and for every 125 individuals treated with high GC doses for the first 3 months, compared with no GC use. Our results broadly agree with previous observational studies showing a dose dependent increased risk of infection associated with (recent) use of oral glucocorticoids.

Clinical efficacy and safety of sirolimus in childhood-onset systemic lupus erythematosus in real world.

To investigate the effectiveness and safety of sirolimus in childhood-onset systemic lupus erythematosus in a real world. This is a retrospective real world clinical study. All childhood-onset systemic lupus erythematosus patients treated with sirolimus in Children's Hospital of Hebei Province China were analyzed. They were treated with sirolimus and followed up regularly. The patients had systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, levels of antidouble-stranded DNA antibody, complement components C3 and C4, 24-hour proteinuria and corticosteroid reduction were recorded at baseline and at 6, 12, and 18 months. Adverse events were also collected. Thirty-two patients were enrolled in the study. SLEDAI-2K were improved on all time-points (P < .05). Complement levels increased and the levels of antidouble-stranded DNA antibody decreased during treatment. The mean dose of prednisone tapered and achieved significant reduction after 12 months therapy (15.4 ± 5.8 mg/d to 4.8 ± 2.1 mg/d; P < .05). Sirolimus was well tolerated and only 5 patients (15.6%) experienced adverse events, all of which were classified as infections (2 bacterial infection and 3 viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were found. Sirolimus use was associated with a decrease in disease activity and ability to tolerate tapering of oral glucocorticoid dose with a favorable risk-benefit profile.

Clinical and laboratory characteristics of patients with articular manifestations of systemic lupus erythematosus

Background. Damage of the joints is one of the typical and often the first signs of systemic lupus erythematosus (SLE), however the peculiarities the of clinical and laboratory changes in patients without articular manifestations (AM) remain insufficiently studied. The purpose was to study the frequency of AM in the patients with SLE and to evaluate its interconnection with clinical and laboratory manifestations of the disease. Materials and methods. 376 patients with SLE were examined. 2 groups were formed: I — with AM presented as arthritis and/or arthralgia at the time of application (n=316), II — without AM (n=60). The involvement of various organs and systems, as well as the levels of inflammatory markers and the spectrum of specific autoantibodies, were evaluated. Results. Patients with SLE and AM had erythematous rash on the face in the form of a “butterfly” more often than the patients without AM (34.1vs. 20.0%, p=0.04). Serositis was more often observed in patients with AM (39.6%) compared to the patients without AM (25.4%, p=0.048). Nephritis with nephrotic syndrome was 4 times more frequent in patients without arthritis/arthralgia compared to the subjects with AM (10.2 vs. 2.6%, p=0.04). The frequency of antiphospholipid syndrome was also significantly higher in patients without AM (25.5 vs. 6.0%, p&lt;0.001). The group of the patients with SLE and AM had a higher frequency of Raynaud’s syndrome (27.5 vs. 15.0%, p=0.046), lymphadenopathy (50.5 vs. 35.6%, p=0.048), heart involvement (62.5 vs. 42.4%, p=0.007), weight loss (13.6 vs. 3.8%, p=0.04) and positivity for antibodies to dsDNA (65.0 vs. 45.7%, p=0.03), than the patients without AM. The median value of SLEDAI was significantly higher in the patients with SLE and AM (11 (6–16) points vs. 7.5 (4–14) points, р=0.01). Also they received significantly higher doses of oral glucocorticoids (10 (10–20) mg/d in prednisolone equivalent) compared to the subjects without AM (6.25 (3.75–12.5) mg/d, p=0.01). Conclusions. Rash on the face in the form of a “butterfly”, serositis, heart involvement, lymphadenopathy, Raynaud’s syndrome, weight loss, and anti-dsDNA positivity are significantly more common in SLE patients with AM. Nephritis with nephrotic syndrome and antiphospholipid syndrome occur more often in patients with SLE without AM. Presence of arthritis/arthralgia in patients with SLE is associated with a higher index of disease of activity and the need for higher doses of glucocorticoids.

Evaluating the Use of Glucocorticoids Among Belimumab-Treated Patients With Systemic Lupus Erythematosus in Real-World Settings Using the Rheumatology Informatics System for Effectiveness Registry.

ObjectiveGlucocorticoids are part of standard therapy for systemic lupus erythematosus (SLE), despite adverse effects associated with long‐term treatment. Belimumab improved clinical manifestations of SLE and reduced glucocorticoid doses in clinical trials and clinical practice; however, associations have not been examined using multi‐institutional electronic health record (EHR) data. Using the Rheumatology Informatics System for Effectiveness registry, we examined glucocorticoid use patterns among belimumab‐treated adults with SLE.MethodsThis retrospective analysis (GSK Study 209267) used EHR prescription records of patients with SLE managed by rheumatologists. Eligible patients had an index date (first belimumab prescription) between January 2014 and June 2018. The primary analysis compared patients' mean daily oral glucocorticoid (prednisone equivalent) dose over the 6 months preindex versus 6 months post index. An exploratory analysis assessed glucocorticoid doses at 12 and 24 months post index for patients with extended follow‐up.ResultsOf the 1987 patients receiving their first belimumab prescription, 767 had available glucocorticoid prescribing data, whereas 204 (primary analysis population) had glucocorticoids prescribed in the 6 months preindex and received belimumab according to the prescribing information for the first 8 weeks post index. The mean (SD) glucocorticoid dose was 12.5 (13.5) mg/day 3 months preindex, reducing to 10.3 (10.6) mg/day over the 6 months post index, and 8.7 (9.4) and 9.0 (9.3) mg/day at 12 and 24 months post index.ConclusionThis study showed reductions in mean daily glucocorticoid dose after belimumab initiation. Several limitations of EHRs for real‐world effectiveness research were identified, which limited interpretation of results and may inform future study designs.

No need of glucocorticoid dose adjustment in patients with adrenal insufficiency before COVID-19 vaccine.

Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna). Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.