Glucocorticoid Prescription Research Articles

Analysis of methotrexate use practice in patients with rheumatoid arthritis and psoriatic arthritis

Background. Pharmacoepidemiological studies play a key role in optimizing pharmacotherapy for various diseases. In particular, significant progress in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) necessitates a detailed analysis of the consumption of disease-modifying antirheumatic drugs. The modern therapeutic concept for these conditions focuses on achieving and maintaining long-term remission, which positions methotrexate (MTX) as a first-line agent, characterized by high effectiveness, safety and advantageous pharmacoeconomic profiles.Objective: to investigate the characteristics of MTX use in real clinical practice among patients with RA and PsA during outpatient medical care.Material and methods. The study comprised two parts: a retrospective cross-sectional analysis of MTX consumption dynamics in 2018, 2020, and 2023 via ATC/DDD (Anatomical Therapeutic Chemical classification, ATC; defined daily dose, DDD) methodology, and a longitudinal non-interventional pharmacoepidemiological study conducted in 2023 using the medical information system “BARS. Healthcare”.Results. The ATC/DDD analysis demonstrated a significant increase in MTX consumption among patients with RA and PsA: from 302,428.6 to 319,114.3 DDDs per 1,000 patients per year for RA, and from 28,157.1 to 310,771.6 DDDs per 1,000 patients per year for PsA in 2018 and 2023, respectively. The most frequently prescribed dose of MT was 15 mg/week. The primary therapeutic combination for 55.8% of patients was “MT + nonsteroidal anti-inflammatory drugs”, with 32.7% of patients also receiving glucocorticoids (GCs) as part of this combination. The study identified a high frequency of prescriptions for proton pump inhibitors, GCs, and cholecalciferol, highlighting the activity of diseases under consideration, potential complications, and the necessity for the prevention of clinically significant drug interactions.Conclusions. The conducted study confirmed that MTX remains the main drug for the treatment of RA and PsA. The ATC/DDD analysis demonstrated a significant increase in MTX consumption in recent years, correlating with its therapeutic effectiveness and accessibility. The high frequency of concomitant prescriptions underscores the complexity of treating RA and PsA and the need for an interdisciplinary approach to ensure safety and efficacy of the therapy.

Clinical phenotypes of sarcoidosis using cluster analysis: a Spanish population-based cohort study.

Sarcoidosis is a clinically heterogenous disease. The objective of this study is the identification of clinical phenotypes using cluster analysis. A model-based clustering relaying on 19 clinical variables was performed in a retrospective cohort of 342 sarcoidosis patients, diagnosed and followed-up from 1999 to 2019 in a tertiary hospital at Northern Spain. Chi-square test and ANOVA were used to compare categorical and continuous variables among groups. Two-sample t-tests and the partition of Pearson's chi-square statistic were used in pairwise comparisons. The Wasfi severity score was calculated and compared among clusters. Cluster analysis identified five groups: C1 (16.1%), C2 (14.3%), C3 (24.3%), C4 (5.0%), and C5 (40.4%). Lung involvement was predominant, ranging from 55.1% (C2) to 100% (C1 and C4). Extrapulmonary involvement was significantly higher in C2 (96.4%) and C3 (98.0%). A significant lower FEV1 percent predicted was detected in C5 (90.5±21.8) versus C1 (102.0±22.9), C3 (102.3±17.6) and C4 (105.8±20.8). The cluster 5 had a lower FVC percent predicted (96.6±18.9) than others, ranging from 108.1±18.0 (C3) to 111.5±21.7 (C4). The prescription of systemic glucocorticoids and non-corticosteroid immunosuppressants was higher in the clusters 1, 3 and 5. Chronicity rates were higher in C3 (31.3%) and C5 (32.6%) compared to C1 (9.1%) and C4 (0%), as well as the Wasfi severity score values. Five phenotypes with different clinical and prognostic characteristics are proposed in our study. Cluster analysis can be a useful tool for identifying clinical patterns in a disease as heterogeneous as sarcoidosis and optimising its management.

Long-Term Mortality Following SARS-CoV-2 Infection in Rural Versus Urban Dwellers With Autoimmune or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From the National COVID Cohort Collaborative.

Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two-year all-cause mortality. Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for two-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher two-year all-cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19-1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two-year post-COVID-19 mortality, whereas risk with nonbiologic or biologic disease-modifying antirheumatic drugs was lower. Rural residence in people with AIRD was independently associated with higher two-year post-COVID-19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among high-risk rural residents.

Treatment of systemic lupus erythematosus: Analysis of treatment patterns in adult and paediatric patients across four European countries

ObjectiveMultiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE). MethodsWe conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy. ResultsWe characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80–88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66–83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults. ConclusionTreatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines.

Association of Cardiovascular Outcomes With Low-Dose Glucocorticoid Prescription in Patients With Rheumatoid Arthritis.

Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long term. We evaluated the cardiovascular risk of long-term glucocorticoid prescription by studying patients on stable disease-modifying antirheumatic drugs (DMARDs). Using two claims databases, we identified patients with RA on stable DMARD therapy for >180 days. Proportional hazards models with inverse-probability weights and clustering to account for multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction [MI]). There were 135,583 patients in Medicare and 39,272 in Optum's de-identified Clinformatics Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person-years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes in adjusted models with predicted one-year incidence of 1.4% (95% confidence interval [CI] 1.2%-1.6%) for ≤5 mg, 1.6% (95% CI 1.4%-1.9%) for >5 to 10 mg, and 1.8% (95% CI 1.2%-2.5%) for >10 mg versus 1.1% (95% CI 1.1%-1.2%) among patients not receiving glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes. Among older patients with more comorbidities and younger patients with higher cardiovascular risk with RA on stable DMARD therapy, glucocorticoids were associated with a dose-dependent increased risk of MI and stroke, even at doses ≤5 mg/day. By contrast, no association was noted among younger, healthier patients with RA.

Are adverse events higher among patients with acute optic neuritis prescribed glucocorticoids? A retrospective, longitudinal cohort study

ObjectiveOptic neuritis (ON) is an acute focal inflammation of the optic nerve routinely treated with glucocorticoids. We aimed to compare adverse events (AE) among glucocorticoid-treated and untreated patients in the...

Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort

ObjectivesWhile glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated...

Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.

It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users. Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency. Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients. GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.

Real-world management of patients with neuromyelitis optica spectrum disorder using satralizumab: Results from a Japanese claims database

BackgroundSatralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. MethodsWe used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. ResultsOf the 131 patients included in the overall population, most were female (90.8 %), aged 18–65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0–351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. ConclusionThese real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.

Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). Patients aged 50years who were prescribed GC (≥ 70mg prednisolone or equivalent; PSL) in the initial 90days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC 5mg PSL/day had a significantly increased fracture risk in the stratum of 30-59days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5mg PSL/day) for 90days in the initial 90days of GC therapy had a significantly increased fracture risk. GC exposure in the initial 90days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Feedback Intervention for the Control of Glucocorticoid Prescription in Primary Care Institutions: A Cluster Randomized Cross-Over Controlled Trial in Southwest China.

The purpose of this study is to assess the effect of glucocorticoid prescription feedback intervention in complex primary care institutions for regulating its inappropriate use. A six-month cluster randomized cross-over controlled trial was conducted in primary care institutions. A total of 347 physicians from 69 participating institutions were randomly allocated to either group A or group B. Both groups were given feedback interventions or serve as control. The feedback intervention comprised two components: a real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and a high-proportion prescription feedback intervention warning system. The primary outcome measure was the 10-day inappropriate glucocorticoid prescription rate, while the 10-day glucocorticoid prescription rate served as secondary outcome measure. At baseline, the 10-day inappropriate glucocorticoid prescription rates were 66.63% and 66.57% in group A and group B, respectively, showing no significant difference (p = 0.140). Following the intervention, group A exhibited a significant reduction in 10-day inappropriate glucocorticoid prescription rate at the crossing point by 13.69% (p < 0.001). In contrast, group B, which served as the control group, experienced an increase of 5.93% (p = 0.037) at the same crossover point. After the crossover point, there was a decrease in 10-day inappropriate glucocorticoid prescription rate for both groups. Group B as the intervention group demonstrated a reduction of 28.22% compared to the crossing point (p < 0.001), whereas group A showed a decrease of 12.20% (p = 0.339). The characteristics of physicians did not significantly influence the inappropriate glucocorticoid prescription rate. The real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and high-proportion prescription feedback intervention warning system can effectively regulate the inappropriate glucocorticoid prescribing behavior of physicians. ISRCTN11747547.

The causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional Mendelian randomization study.

Several observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa. We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings. In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations. This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.

Nationwide prevalence of glucocorticoid prescriptions over 17 years and osteoporosis prevention among long-term users.

Glucocorticoid steroids are frequently prescribed, and side effects are well-known, such as glucocorticoid-induced osteoporosis. Our aim was to estimate the nationwide trend in the prevalence of glucocorticoid steroid prescriptions over 17 years and to elucidate the proportion of patients on long-term glucocorticoid steroid therapy who receive active bone protective therapy. As well as to examine which medical specialties prescribe glucocorticoid steroids the most. This study was a retrospective observational registry study extended over 17 years (2003-2020). Data were retrieved from the Icelandic Prescription Medicine Register on all delivered glucocorticoid steroids (Anatomic therapeutic chemical code: H02AB) for oral use. Long-term users were defined as those who annually received ⩾90 defined daily doses of glucocorticoid steroids. Annually, 3.8% of the population received oral glucocorticoid steroids, from 3.3% in 2006 to 4.3% in 2017. Prednisolone was most frequently prescribed. Females dispatched glucocorticoid steroid prescriptions more often than males (55.8%). Males and females reached their peak prevalence between the ages of 60 and 70. General practitioners most often prescribe glucocorticoid steroids, followed by physicians in training, rheumatologists, internists, and medical students. Of those who received prescriptions for glucocorticoid steroids, 12.2%-18.1% were classified as long-term users. A declining number of patients have been receiving bone-protective therapy in recent years. Only 13.0% of chronic users received bone protective therapy in 2020. The use of glucocorticoid steroids has increased during the last 2 decades despite improvements in treatment for inflammatory disorders. The prevalence of long-term users has remained stable. Meanwhile, the use of parallel active bone-protective therapy among long-term users of glucocorticoid steroids is declining. Thus, improvements in prophylaxis for corticosteroid-induced osteoporosis are urgently needed for patients who require long-term treatment with glucocorticoid steroids.

Бетагерпетические кератиты. Обоснование диагноза и тактики ведения пациентов

Relevance. This publication presents an algorithm for the management of patients with recurrent keratitis associated with betaherpesviruses and outlines the possibilities of laboratory and instrumental diagnostics. Purpose. To systemize the algorithm for the management of patients with superficial keratitis associated with betaherpesviruses confirmed by confocal microscopy. Material and methods. A group of 21 patient (21 eye) with superficial keratitis associated with betaherpesviruses was under observation during 12 months. The diagnosis was made on the basis of confocal microscopy results, clinical picture and results of laboratory tests. Each patient received a two-stage treatment with nucleoside analogues locally and systemically; treatment with anti-inflammatory and reparative medicine. Results. Remission as a result of the treatment was achieved in 20 of the 21 patients. Conclusion.The only reliable diagnostic method of keratitis associated with betaherpesviruses is a confocal microscopy, with identification of betaherpesvirus specific «owl's eye» cells. In view of frequent recurrence leading to increase of cornea opacity area, therapy of keratitis associated with betaherpesviruses requires a two-stage treatment. In first stage it is mandatory to prescribe increased dosages of nucleoside analogues, second stage requires prescription of local glucocorticoids and long-term reparative treatment. Key words: keratitis, herpesviruses, cytomegalovirus, human herpesvirus 6, «owl's eye» cells

State-of-the-art trends in the treatment of immune-mediated inflammatory kidney diseases: Translation of the fundamental science into clinical practice. A review

Immune-mediated kidney diseases like glomerulonephritis and tubulointerstitial nephritis are not the most common cause of chronic kidney disease in the population, however the difficulties in their management, as well as a more rapid deterioration of kidney function, compared to diabetes mellitus and hypertension, justify the importance of this problem for internal medicine. Due to the fundamental discoveries in pathology and to the introduction of various methods of laboratory and instrumental investigation in the second half of the XX century substantial progress was made in the diagnostic approaches and treatment of these conditions. State-of-the-art diagnostic approach requires complex evaluation of the clinical, laboratory and morphological data to identify the nosological form of the disease. The accumulation of knowledge in the field of diseases' pathogenesis led to the revision of the current classification of glomerulonephritis that should be based on the immunopathogenesis of these conditions. The following phenotypes were suggested: autoimmunity-related, autoinflammation-related, alloimmunity-related, infections-related, and monoclonal gammopathy-related. The assessment of disease activity and chronicity in the kidney tissue should be mandatory. Personalized selection of the optimal treatment modality on the basis of the diagnosis, severity, and individual features of the patient is currently possible. The leading trends include rational prescription of glucocorticoids (steroid-sparing regimens) and cytotoxic agents, e.g. cyclophosphamide, as well as the introduction of multitarget regimens that include biologic agents or small molecules selectively suppressing B-cells or various complement pathways. Another mandatory component of treatment on par with immune suppression is nephroprotective therapy, which currently comprises not only traditional renin-angiotensin-aldosterone antagonists, but also endothelin receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Current guidelines emphasize the importance of the non-pharmacological interventions for the implementation of the nephroprotective strategy. Rational combination of the aforementioned approaches allows for the optimization of the management of patients with immune-mediated kidney diseases, although it requires high competencies and strict adherence to the principles of the evidence-based medicine from the healthcare providers.

Trends and Patterns of Systemic Glucocorticoid Prescription in Primary Care Institutions in Southwest China, from 2018 to 2021.

The purpose of this study was to investigate the prescribing patterns and usage trends of systemic glucocorticoids in primary care institutions located in Southwest China from 2018 to 2021. A retrospective cross-sectional analysis of systemic glucocorticoids prescriptions was conducted in 32 primary care institutions located in Southwest China between 2018 and 2021. Prescriptions of systemic glucocorticoids were classified as appropriate or inappropriate use. Inappropriate use was further classified into (1) inappropriate indications and (2) inappropriate selection of glucocorticoids. Generalized estimation equations were employed to investigate the factors associated with inappropriate utilization of systemic glucocorticoids. The seasonal autoregressive integrated moving average (SARIMA) model was employed to predict the rate of inappropriate glucocorticoids prescriptions. A total of 203,846 (92.89%) prescriptions were included, both the number of systemic glucocorticoids prescriptions and inappropriate prescriptions increased in winter. Diseases of the respiratory system (68.90%) were the most frequent targets of systemic glucocorticoids use. Of all prescriptions, 73.18% exhibited inappropriate indications, while 0.05% demonstrated inappropriate selection. The utilization of systemic glucocorticoids was deemed inappropriate for diseases of the respiratory system (94.19%), followed by diseases of the digestive system (87.75%). Physicians, who were female or younger than 33 years old, possess lower levels of education and professional titles and exhibit a higher likelihood of inappropriately prescribing systemic glucocorticoids. The phenomenon of inappropriate glucocorticoids use was commoner among male patients aged 65 years and older. After conducting model verification, it was determined that the SARIMA model could be used to predict the monthly rate of inappropriate systemic glucocorticoids prescriptions in primary care institutions in southwest China. The inappropriate use of systemic glucocorticoids remains a significant concern in primary care institutions. In this regard, continuing education and professional knowledge training of physicians should be strengthened in the future.

Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID-19 Outcomes: A Population-Based Cohort Study.

We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID-19 outcomes in a population-based cohort study. Participants were 18 years or older, tested positive for SARS-CoV-2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS-CoV-2 test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non-TNFi biologics or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID-19 outcomes were hospitalizations for COVID-19, ICU admissions, and deaths within 60 days of a positive test. Exposure score-overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID-19 outcomes. From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non-TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID-19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], and glucocorticoids: 1.63 [1.36-1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34-4.74], immunosuppressants: 2.88 [1.73-4.78], and glucocorticoids: 1.86 [1.37-2.54]. Only glucocorticoids use was associated with a significant increase in 60-day mortality: 1.58 [1.21-2.06]. No other IIAs displayed statistically significant associations with severe COVID-19 outcomes. Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID-19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.

FRI129 Adrenal Insufficiency In Olmsted County, MN, USA: A Population-Based Study

Abstract Disclosure: M. Moazzami: Grant Recipient; Self; Rochester Epidemiology Project. S. Achenbach: None. E. Atkinson: None. I. Bancos: None. Background: Epidemiology of adrenal insufficiency (AI) is incompletely characterized with most data originating from referral centers and registries. We aimed to determine the incidence, morbidity index, risk of hospitalizations, and mortality in patients with AI living in Olmsted County, Minnesota. Methods: We assessed the standardized incidence rate, morbidity index, risk of hospitalizations and mortality of AI in residents (aged 18+) in Olmsted County, MN, USA, from Jan 1, 2005, to December 31, 2021. The data was collected using the Rochester Epidemiology Project (REP), a database of medical records for all Olmsted County residents since 1966. Incidence rates were standardized for age and sex according to the 2020 US white population. Sex- and age- matched referent subjects were selected from the REP. AI was defined based on presence of oral chronic glucocorticoid therapy (hydrocortisone, prednisone, prednisolone, or dexamethasone) defined as (1) any hydrocortisone use or (2) 6 months of consecutive use of prednisone, prednisolone, or dexamethasone or (3) two AI diagnosis codes 6+ months apart plus at least one glucocorticoid prescription within 1 year of the second diagnosis. Elixhauser morbidity index was used. Findings: Between 2005 and 2021, 5419 patients were diagnosed with AI (median age of 62 years, range 18-103), 56% women). Overall standardized incidence rates for AI increased from 206 (95% CI 174-238) in 2005 to 252 (223-280) per 100 000 person-years in 2021. At baseline, patients with AI had a higher morbidity index (median 3 vs median 1, p &amp;lt;0.001) and a higher history of hospitalizations within 5 years prior to baseline (57% vs 30%; p&amp;lt;0.001) when compared to referent subjects. When comparing patients with AI to referent subjects, and after adjusting for age, sex, morbidity index and prior history of hospitalizations, patients with AI were more likely to be hospitalized during follow-up (aHR 1.4, 95% CI 1.3-1.5). When comparing patients with AI to referent subjects, and after adjusting age, sex, and morbidity index, patients with AI had higher mortality (aHR 1.7, 95% CI 1.6-1.9). Patients with AI demonstrated a higher risk of dying from musculoskeletal disorders (aHR 4.9, 95% CI 2.2-10.8), respiratory disorders (aHR 4.7, 95% CI 3.3-6.6), neoplasms (aHR 2.4, 95% CI 2.0-2.9), and infectious disorders (aHR 2.3, 95% CI 1.2-4.3) than referent subjects. Interpretation: We demonstrate an increase in AI incidence between 2005 and 2021. Surprisingly, even after controlling for morbidity and prior hospitalizations, patients with AI were more likely to be hospitalized. In comparison to referent subjects, mortality was higher in patients with AI, even after adjustment for morbidity index. Presentation: Friday, June 16, 2023

SAT293 Improving Prescribing For Emergency Glucocorticoid Kits In Primary Adrenal Insufficiency

Abstract Disclosure: M.W. Porter: None. K.E. Anderson: None. K.M. Myers: None. S. Friedman: None. S.U. Perez-Martinez: None. J. Adamczyk: None. V. Patel: None. C.D. Hendrickson: None. Introduction: Primary adrenal insufficiency (PAI) is a condition defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and mineralocorticoids. Adrenal crisis is a complication of PAI which studies suggest approximately 1 in 12 patients will experience in the coming year, with an associated mortality rate of 0.5/100 patient years.1 Endocrine Society guidelines recommend that every PAI patient should be equipped with a glucocorticoid injection kit for emergency use.2 Despite this recommendation, rates of prescription are variable with recently published survey data demonstrating ranges of 30% 3 to 86.5%.4 Aim: The aim of this quality improvement project was to increase emergency glucocorticoid injection prescribing to greater than 80% of patients with Addison’s disease. Methods: Our project first identified baseline data on active emergency glucocorticoid prescription for patients with diagnosis of Addison’s disease and a clinical encounter within the prior year.We then engaged clinical pharmacist stakeholders who were presented these patients and proactively contacted each directly, facilitating prescriptions being sent in the most affordable method to the pharmacy of choice and then notifying the clinician. Results: Retrospective analysis into prescribing patterns at our clinic demonstrated a mean of 54.7% PAI patients with an active prescription for emergency glucocorticoid during 2021. Following a transition period after initiating the intervention in March 2022 there was a statistically significant increase in mean active prescriptions to 88% maintained from May to Nov. 2022 as demonstrated on a statistical process control chart. Discussion/Conclusion: While emergency glucocorticoid is recommended for all patients with PAI, we identified a deficit in prescription patterns that appears consistent with previous data. Numerous challenges exist for consistent prescription practices; however, our intervention demonstrated a reproducible model for increasing access to potentially lifesaving medication in patients with PAI.

The impact of proton pump inhibitors on the course of ulcerative colitis: a cohort study of over 10,000 newly diagnosed patients in Norway

Background and Aims Proton pump inhibitors (PPI) affect the gastrointestinal microbiota, which is thought to play a role in the pathogenesis of ulcerative colitis (UC). Previous studies suggest an association between PPI use and risk of incident UC as well as disease course. The aim of the study was to examine if PPI exposure is associated with disease course in UC patients. Methods A national cohort consisting of all newly diagnosed UC patients from 2010 to 2020 was defined combining data from Norwegian registries. PPI exposure was included as a time dependent variable with a 30 day time lag from starting the drug. Outcomes were starting advanced therapies including anti-TNF, systemic glucocorticoids, any additional systemic anti-inflammatory medication and undergoing colectomy during follow-up. Time-dependent Cox regressions included the variables PPI use, first systemic glucocorticoid prescription, first UC hospitalization, age-groups and sex. Results The study cohort consisted of 10,149 patients with median age 40 years (IQR 27–56) and 56% males. PPI use independently increased the risk of starting advanced therapies (HR 1.54, 95% CI 1.36–1.73, p < 0.005), starting systemic glucocorticoids (HR 1.20, 95% CI 1.07–1.34, p < 0.005), starting any additional anti-inflammatory treatment (HR 1.18, 95%CI 1.05–1.32, p < 0.01) and undergoing colectomy (HR 1.52, 95%CI 1.17–1.98, p < 0.005). Conclusions PPI use was associated with unfavorable outcomes including advanced therapy initiation, additional anti-inflammatory medications and undergoing colectomy. Although further studies are needed, the evidence suggests that PPIs could affect the course of UC and should be used cautiously in UC patients.