High-dose Glucocorticoids Research Articles

An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia.

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.

Ocular surface and in vivo confocal microscopic findings in patients with active tyhroid eye disease treated with glucocorticoids.

To evaluate the effect of treatment with high-dose glucocorticoids (HDG) on ocular surface parameters and in vivo confocal microscopy (IVCM) findings in patients with active thyroid eye disease (TED). This study included 15 active TED patients treated with a cumulative HDG dose of 4.5g (500 mg and then 250 mg for 6 weeks each). Disease activity was assessed by the clinical activity score (CAS), Graves' Orbitopathy-specific Quality of Life (GO-QoL) questionnaire, ocular surface disease index (OSDI), tear break-up time(T-BUT), ocular surface staining and IVCM. The mean follow-up time was 48.6 months. The treatment resulted in a significant improvement in the T-BUT, ocular surface staining values. In comparison to the baseline, a notable reduction in CAS, OSDI and an increase in GO-QoL were seen after one year. IVCM showed a significant decrease in the number of dendritic cells, activated keratocytes, the degree of tortuosity, there was also a significant increase in the number of basal epithelial cells and total nerves over one-year period. All of those changes remained stable during the follow-up period. HDG treatment results in a sustained decrease in corneal inflammatory cells, an increase in tear film stability, and an improvement in disease symptoms and QoL scores for up to 4 years.

Annals for Hospitalists - February 2023

Annals for Hospitalists - February 2023

Glucocorticoid therapy as first-line treatment in primary hypophysitis: a systematic review and individual patient data meta-analysis.

High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear. We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual-patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs. 6.5-12 vs. >12 weeks) of glucocorticoid treatment according to disease severity. 153 PAH patients from 83 publications were included. The median age at presentation was 41(32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with intravenous (91.7%) as compared to oral (54.5%) route, high dose (100%) and very-high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in intravenous (54.8% vs. 28.1% oral, p=0.033) route and increasing glucocorticoid dose group (0% vs. 38.1% vs. 57.1%), attaining statistical significance (p=0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. Need for rescue therapy with lower with intravenous route (38% vs 17.5%, p=0.012) and with increasing glucocorticoid doses (53.3% vs. 34.3% vs. 17.3%, p=0.016). In severe disease, visual field and corticotroph axis recovery was significantly higher with intravenous route and very-high dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment. Very high-dose glucocorticoids by intravenous route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.

A severe cerebral infarction associated with giant cell arteritis, which developed during tocilizumab therapy and was successfully treated with intravenous cyclophosphamide.

Giant cell arteritis (GCA) is a large vessel vasculitis that primarily involves aorta and its major branches. Cerebral infarction is a serious complication that can occur secondary to GCA in up to 3% of patients with a mortality rate of over 50%. Due to the rarity of this severe complication, no therapeutic strategies are currently available. Furthermore, despite the recent progress in molecular-targeted therapy for GCA, it remains unknown whether tocilizumab is effective for severe ischemic complications such as cerebral infarction. The accumulation of individual cases in which this fatal complication could be treated is apparently required to build a better management of the disease. We present our case of GCA that developed severe cerebral infarction during high-dose glucocorticoid and tocilizumab therapy, and its symptoms and image findings were improved by switching to intravenous cyclophosphamide. Our case suggests that an intensive immunosuppressive therapy, including cyclophosphamide, may be necessary to stabilise this fatal complication of GCA.

Rapidly Progressive Pauci-Immune Glomerulonephritis with Aberrant Fibrinoid Necrosis Associated with Atezolizumab, an Immune Check Point Inhibitor: A Case Report and Review of Literature

Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity of ICIs is limited. Herein, we present a patient with lung cancer treated with atezolizumab, an IgG1 monoclonal antibody aimed at the programmed death ligand 1 (PD-L1), who presented with vasculitic skin rash and rapidly deteriorating renal function, new onset of significant glomerular hematuria and proteinuria. The renal biopsy revealed acute necrotizing pauci-immune vasculitis, with fibrinoid necrosis. The patient received a course of high-dose glucocorticoids with recovery of renal function and skin lesions. Further immunosuppressive therapy was withheld, due to active malignancy in the lung, while oncology consultation recommended the continuation of treatment with atezolizumab, as the patient had shown substantial response.

Glucocorticoid Therapy in COVID-19-Induced Organizing Pneumonia: A Rare Occurrence.

Background Although the incidence of post-COVID-19 organizing pneumonia (OP) is low, the mortality and morbidity in select patients appear to be high. Anticipating specific populations who may be at higher risk and initiating treatment earlier could reduce mortality. Research question Does treatment with high dose, standard dose, or no glucocorticoids for COVID-19 infection impact the incidence and clinical outcome in COVID-19-induced OP? Study design and methods This was a single-center, retrospective, observational cohort study conducted from 03/01/2020 to 06/30/2021 in hospitalized patients over the age of 18 with confirmed COVID-19 infection and computed tomography (CT) scan evidence of OP. Institutional review board (IRB) approval was obtained from the institution (STUDY00002241). Patients'demographics and oxygen requirements at the time of diagnosis, at the time of discharge, and at one, three, six, 10, and 12 months post-discharge were obtained. The dose, duration, and choice of glucocorticoid therapy were recorded for each subject, as well as oxygen requirements during hospitalization. Despite radiological evidence of OP, patients on minimal supplemental oxygen requirements did not receive high-dose or long-duration glucocorticoidtherapy. Results A total of 881 patients were admitted with COVID-19, of which 42 met the study criteria. Three patients underwent a lung biopsy to confirm the diagnosis of organizing pneumonia. All other patients were diagnosed based on CT imaging and clinical presentation. Of the patients, 17% did not receive any steroid treatment, while 36% received dexamethasone and 43% received prednisone. The most common oxygen requirement at the time of discharge for steroid-treated patients was nasal cannula (55%) and room air (29%). The incidence of OP in this patient population was 0.05 with a mortalityrate of 14%. Interpretation and relevance The incidence of post-COVID-19 OP appears to be lower than anticipated. Steroids for patients on lower supplemental oxygen requirements were discontinued although they had radiological evidence of OP. Patients who were on higher supplemental oxygen requirements at 10 days were continued on steroids regardless of imaging. The decision to continue steroids should be based on individual patient characteristics such as oxygen requirements. In the future, larger multicenter cohort studies would help understand further treatment of post-COVID-19-associated OP. Anticipating specific populations who may be at higher risk and starting treatment earlier could help reduce mortality.

Pregnancy-related hypophysitis revisited.

The aim of the study is to assess the distinguishing features of pregnancy-related hypophysitis (PR-Hy) compared to non-pregnancy autoimmune hypophysitis and to evaluate the changing therapeutic approaches and outcomes in PR-Hy over time. Retrospective analysis of all published cases with PR-Hy and 6 own cases. A PubMed search was performed and abstracts screened for publications with information on cases with PR-Hy from which full-text review was performed. Clinical features, diagnostic findings, and outcome in relation to treatment modalities in PR-Hy were assessed. One hundred and forty-eight cases with PR-Hy were identified. PR-Hy was significantly delimited from non-PR-Hy by the frequent occurrence of the chiasmal syndrome (50% vs 13%, P < .0001), higher rate of intrasellar origin (94% vs 74%, P = .0005), lower rate of pituitary stalk involvement (39% vs 86%, P < .0001), and low rate of diabetes insipidus (12% vs 54%, P < .0001). The role of surgery in PR-Hy decreased over time while noninvasive treatment modalities increased. The recurrence rate after high-dose glucocorticoid therapy (33%) was high and exceeded that of surgery (2%) and conservative management (2%). In contrast to initial reports on PR-Hy, recent literature regarding outcome of mother's and child's health was positive. The frequency of spontaneous preterm delivery was not increased. Recurrent PR-Hy in a subsequent pregnancy was reported in only two females. PR-Hy has distinct features that delineate the disorder from non-PR-Hy. With increasing experience in diagnosis, availability of adequate replacement therapy, and improved treatment modalities, PR-Hy has lost its threat and the outcome is encouraging.

Perioperative Low-Dose Prednisolone Treatment Has Beneficial Effects on Postoperative Recovery and Anastomotic Healing in a Murine Colitis Model.

High-dose glucocorticoid treatment has been identified as a risk factor for anastomotic leakage in patients with inflammatory bowel disease [IBD] undergoing bowel resection surgery. By contrast, active disease during surgery is also associated with elevated morbidity. Perioperative low-dose treatment might be beneficial regarding postoperative outcomes by controlling disease activity. The present study is the first to investigate the dose-dependent effect of perioperative prednisolone therapy in a murine IBD model combining dextran sodium sulphate [DSS] colitis with intestinal anastomosis surgery. In 84 10-week-old wild-type mice, a colorectal anastomosis was performed using a microsurgical technique. Half the animals received induction of chemical colitis with 2% DSS via drinking water prior to surgery. In both groups, one-third of the animals received daily oral administration of high-dose [0.533 mg/kg] and one-third low-dose [0.133 mg/kg] prednisolone. Evaluation was performed on postoperative days 3 and 7. While high-dose prednisolone treatment led to an increased anastomotic leakage rate in mice under colitis, low-dose prednisolone treatment limited preoperative disease activity and did not influence the leakage rate. Histological examination showed a beneficial effect of low-dose prednisolone treatment on microscopic abscess formation at the anastomotic site in DSS mice as well as an increased anastomotic healing score. We demonstrate a beneficial effect of perioperative short-term low-dose prednisolone treatment on intestinal anastomotic healing in the context of colitis. Perioperative use of short-term low-dose prednisolone treatment might be beneficial in IBD patients who need to undergo surgery during active disease.

Effects of different doses of glucocorticoids on postoperative atrial fibrillation: a meta-analysis

BackgroundPostoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery, and its occurrence is closely related to inflammation. This paper intends to apply meta-analysis to investigate the effect of glucocorticoids on POAF.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched using the internationally recognized systematic evaluation and retrieval strategy. Two review authors independently selected relevant studies and extracted data based on the Cochrane handbook for systematic reviews of interventions approach. Stata 17 was used for data analysis. In the subgroup analysis, we grouped the participant data according to differences in glucocorticoids dose and type of surgery. At the same time, we also conducted a meta-analysis on the possible infection and gastrointestinal injury caused by glucocorticoids use.Results27 studies and 14,442 patients were finally included. Results from the random-effects model indicated that the incidence of POAF was lower in glucocorticoid group (RR 0.80, 95% CI 0.71–0.92, P = 0.001). According to the subgroup analysis result, low doses of glucocorticoids reduced the incidence of POAF (RR 0.81, 95% CI 0.71–0.92, P = 0.001). The effect of high doses glucocorticoids on the POAF was not statistically significant (RR 0.81, 95% CI 0.56–1.19, P = 0.286). In the coronary artery bypass grafting (CABG) subgroup, the glucocorticoids reduced the incidence of POAF (RR 0.71, 95% CI 0.58–0.87, P = 0.001). In the CABG OR Valvular Surgery group, the effect of glucocorticoids on POAF was not statistically significant (RR 0.88, 95% CI 0.75–1.03, P = 0.108). 15 studies documented postoperative complications of infection, two studies were excluded from the system because the end point event was 0, and meta-analysis showed no increased risk of infection from glucocorticoid use (RR 0.85, 95% CI 0.68–1.06, P = 0.158). Eight studies documented the effects of glucocorticoids on gastrointestinal diseases, and meta-analysis showed no differences between the two groups (RR 1.12, 95% CI 0.83–1.50, P = 0.450).ConclusionThe use of glucocorticoids can reduce the incidence of POAF. The subgroup analysis result showed that low-dose glucocorticoids were more effective than high-dose glucocorticoids in inhibiting POAF. The use of glucocorticoids in CABG alone can better inhibit the occurrence of POAF. The effects of glucocorticoids on infection and gastrointestinal injury were not statistically significant.Review registration: PROSPERO, CRD42022304521.

Photogallery of diseases of the oral mucosa. Part I

Nowadays, more than 300 diseases of the oral mucosa have been established in the scientific literature. Since pemphigus vulgaris and lichen planus can mimic many other skin conditions it could be difficult to make the diagnosis according only to clinical features. Moreover, pemphigus vulgaris is known to be an autoimmune life-threatening disorder which necessarily need to be treated with high doses of systemic glucocorticoids, whereas lichen planus in some cases can be transformed into squamous cell carcinoma.&#x0D; The drug associated erythema and the herpes associated erythema multiforme both affect not only the oral mucosa but also the skin, which makes differential diagnosis easier. Nevertheless, in our practice we can encounter only the oral cavity involvement. Previously, StevensJohnson syndrome was considered as severe form of erythema multiforme affecting both the skin and the oral mucosa.&#x0D; Additionally, cheilitis can be observed in patients with atopic dermatitis even in the remission stage.&#x0D; Furthermore, MelkerssonRosenthal syndrome is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips, and the development of folds and furrows in the tongue.

Better design leads to better results - Importance of virological outcome design in clinical trials for antiviral treatment of coronavirus disease 2019.

Better design leads to better results - Importance of virological outcome design in clinical trials for antiviral treatment of coronavirus disease 2019.

Rheumatological side effects of checkpoint inhibitors and their treatment

The spectrum of tumors for which checkpoint inhibitor (CI) treatment is used is constantly expanding. The European Medicines Agency has currently approved nine CIs: one anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CI, one anti-lymphocyte activation gene 3 (LAG-3) CI, four anti-programmed cell death protein 1 (PD-1) CIs and three anti-programmed death ligand 1 (PD-L1) CIs. By blocking immune checkpoints the physiological downregulation of T cell activity against autologous tissue is prevented. This results in an immunologically unregulated activation of T cells directed against malignant cells. Healthy tissue also expresses antigens and thereby continuously activates autologous T cells. Thus, the blockade of immune checkpoints can lead to T cell activity against healthy tissue (immune-related adverse events, irAE). The irAEs can occur in any organ system and approximately 10% of all patients under CI treatment develop rheumatological irAEs, mostly arthralgia and myalgia. The classification criteria of rheumatological diseases do not need to be met to initiate treatment and the primary goal of treatment of irAEs is to enable continuation of CI treatment. Rheumatological irAEs should be recognized and treated quickly. In the treatment of musculoskeletal irAEs, three stages can be defined. In the first stage, nonsteroidal anti-inflammatory drugs or intra-articular as well as systemic glucocorticoids are used. In the second stage, conventional synthetic and in the third stage, biologic disease-modifying antirheumatic drugs are used. The most severe musculoskeletal irAE is myositis with cardiac and/or respiratory involvement and/or myasthenia gravis. In addition to high-dose glucocorticoids, intravenous immunoglobulins or plasma exchange are used in treatment.

Continuous Glucose Monitoring of Steroid-Induced Hyperglycemia in Patients With Dermatologic Diseases.

Systemic administration of glucocorticoids is a mainstay therapy for various inflammatory diseases and may lead to hyperglycemia, which carries the risk of worsening preexisting diabetes and triggering steroid-induced diabetes. Therefore, we aimed to identify patients at risk and to quantify severity of steroid-induced hyperglycemia (SIH) by continuous glucose monitoring (CGM) in hospitalized patients needing systemic glucocorticoid treatment. This prospective study included 51 steroid-naive, dermatological patients requiring systemic high-dose glucocorticoid treatment at the Department of Dermatology of the University Hospital Essen. After careful diabetes-specific assessment at admission, glucose monitoring was performed using a CGM system and glucose profile was analyzed in patients with and without SIH. SIH occurred in 47.1% of all treated patients, and a relevant part of patients with initial normoglycemia developed SIH (2/10 patients). Doubling of SIH incidence was observed with each severity grade of dysglycemia (4/10 in prediabetes; 9/10 in diabetes). Patients with SIH spend nearly 6 hours daily above targeted glucose range, and severe hyperglycemia was observed for 1.2 hours/day. Our study underlines the need for dedicated glucose monitoring in dermatologic patients on systemic glucocorticoid therapy by demonstrating its impact on glucose metabolism.

Outcomes of Patients Newly-diagnosed with Systemic Lupus Erythematosus Managed in a Tertiary Training and Referral Hospital in the Philippines.

To determine the one-year outcomes of newly-diagnosed patients with systemic lupus erythematosus (SLE) in a tertiary government hospital in Manila, Philippines. After ethics approval, we reviewed the medical records of a cohort of 44 newly-diagnosed SLE patients at 6- and 12-months post-diagnosis in 2018-2019. The outcomes of interest were: modified lupus low disease activity state as defined (mLLDAS), remission, hospitalization, 30-day readmission, organ damage, and mortality. The patients were predominantly young females (mean age of 29 ± 9.9 years). There was an average interval period of six months between onset of symptoms and diagnosis (6.4 ± 10.8 months). The most common manifestations were mucocutaneous (86.4%), hematologic (63.6%), musculoskeletal (61.4%), and renal disorder (47.7%). There was at least one positive serologic test in 88.7%. Five patients (11.4%) had comorbidity, usually hypertension (9.1%). The initial lupus treatment consisted of moderate to high doses of glucocorticoids and hydroxychloroquine. Patients with life-threatening or organ-threatening disease, usually nephritis, received cyclophosphamide, azathioprine, or mycophenolate mofetil. One patient received rituximab. Fewer patients with nephritis received cyclophosphamide infusions during the first six months compared to the later six months.Most of the hospitalizations (34/36) occurred during the first six months and 22 of these were for diagnosis. Seven patients had more than one hospitalization and five (20%) had 30-day readmissions. mLLDAS was achieved by 15 (34.1%) and 30 (68.2%) patients at 6- and 12-months, respectively. Only one patient was in remission a year after diagnosis. Seven patients (15.9%) were assessed with organ damage, six (13.64%) of them at 6-months post-diagnosis. Organ damage was most commonly renal. Four (9.1%) patients died, all during their initial hospitalization. In our population observed over a period of one year (2018-2019), there was a very low rate of remission (1/44, 2.3%), mLLDAS in 68.2%, and organ damage in 15.9%. Most of the hospitalizations (65%) were for the diagnosis of lupus and all deaths (9.1%) occurred during this first hospital confinement. We must intensify our efforts to (1) achieve earlier diagnosis, (2) deliver optimal lupus treatment and supportive care during the first lupus hospitalization, and (3) initiate early and persistent immunosuppressive treatment for nephritis to improve outcomes for our patents with SLE.

Combination of granulomatosis with polyangiitis with COVID-19: difficulties in differential diagnosis and treatment

The article presents a prospective clinical observation with a fatal outcome in a patient with severe granulomatosis with polyangiitis (GPA) complicated by COVID 19 on the background of immunosuppression. At the onset of the disease, there were difficulties in making a diagnosis; differential diagnosis between eosinophilic granulomatosis with polyangiitis (EGPA) and GPA was carried out. Against the background of combined therapy — the use of high and ultra-high doses of glucocorticoids (GC) and cytostatic drugs, a short-term improvement was noted. However, within a year and a half of treatment, it was not possible to achieve remission of the disease. Taking into account the ineffectiveness of the therapy, by the decision of the medical commission, the patient was prescribed genetically engineered biological therapy rituximab (RTM). There was a decrease in the activity of the disease, the achievement of depletion of B-cells. During the pandemic period, despite observing the isolation regime, the patient fell ill with a coronavirus infection. Immunosuppression contributed to severe infection. After the infection was treated, the activity of vasculitis increased, which required the repeated administration of RTM for health reasons. During the therapy it was short-term stabilization of the condition. But after short period — fever, an increase in respiratory failure, the development of neutropenia. Taking into account the initial lesion of the lungs in the patient, differential diagnostics was carried out between the complications of coronavirus infection and the activity of the underlying disease. Despite anti-inflammatory, anticoagulant, antibacterial therapy, the patient's condition progressively worsened, respiratory failure increased, hemoptysis appeared. Spontaneous pneumothorax on the right was diagnosed, pneumomediastinum. After repeated negative PCR results, the causative agent of SARS COV-2 was again detected in smears. The immediate cause of death, according to clinical observation and autopsy, was severe respiratory failure, thrombosis in small vessels of the lungs in a patient with a new coronavirus infection against the background of immunosuppression for GPA.

Bone mineral density in patients diagnosed with giant cell arteritis taking glucocorticoids: a case-control study.

The standard treatment for GCA is high-dose glucocorticoids (GCs). It is unknown whether GCs are more detrimental to BMD at the spine or the hip. The aim of this study was to investigate the effect of GCs on BMD at the lumbar spine and hip in patients with GCA being treated with GCs. Patients who were referred for DXA at a hospital in the north-west of England between 2010 and 2019 were included. Two patient groups were identified: patients with GCA on current GC (cases) were matched 1:4 based on age andbiological sex to those referred to the scanner with no indication for scanning (controls). Logistic models were fitted looking at the spine and hip BMD, unadjusted and adjusted for height and weight. As would be expected, this gave an adjusted odds ratio (OR) of 0.280 (95% CI 0.071, 1.110) at the lumbar spine, OR of 0.238 (95% CI 0.033, 1.719) at the left femoral neck, OR of 0.187 (95% CI 0.037, 0.948) at the right femoral neck, OR of 0.005 (95% CI 0.001, 0.021) at the left total hip and OR of 0.003 (95% CI 0.001, 0.015) at the right total hip. The study has shown that patients diagnosed with GCA receiving GC treatment have a lower BMD at the right femoral neck, left total hip and right total hip compared with controls in patients of the same age and biological sex after adjusting for height and weight.

Glycemic control using intermittently scanned continuous glucose monitoring in patients with diabetes requiring methylprednisolone therapy for severe COVID-19.

In patients with severe coronavirus disease 2019 (COVID-19) with diabetes, glycemic control is essential for a better outcome, however, we face difficulty controlling hyperglycemia induced by high-dose glucocorticoids. We report five cases of severe COVID-19 patients with diabetes, whose glycemic control was managed using an intermittently scanned continuous glucose monitoring (isCGM) system during methylprednisolone therapy. Patients using isCGM showed significantly lower average blood glucose levels and significantly higher total daily insulin dose during the methylprednisolone therapy, compared to patients under regular blood glucose monitoring. The use of isCGM enables remote glucose monitoring, and this can reduce the risks of healthcare workers who have frequent contact with the patients. Thus, we suggest that using isCGM should be considered in hospitalized patients with diabetes under the COVID-19 pandemic to achieve better glycemic control and to minimize the possible risks of healthcare workers.

Predictors of biologic disease modifying antirheumatic drugs withdrawal due to the development of adverse events in patients with rheumatoid arthritis

Currently, a large number of highly effective biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are used for the treatment of rheumatoid arthritis (RA). However, in addition to effectiveness, it is necessary to evaluate the risk of adverse events (AEs) when using them.Objective: to determine the predictors of bDMARDs and tsDMARDs discontinuation due to AEs in patients with RA.Patients and methods. The study included 661 patients with RA who took bDMARDs and tsDMARDs. The search for predictors of targeted therapy discontinuation due to AEs was carried out in two stages. At the first stage, using the Kaplan-Meier method, we selected indicators that showed the greatest significant single-factor relationship with the duration of retention on therapy. At the second stage, significant independent indicators were obtained by iterative selection of variables within the multivariate proportional risk model according to Cox.Results and discussion. The presence of rheumatoid nodules (p&lt;0.001), high doses of glucocorticoids (GC; p&lt;0.001), low doses of methotrexate (MT; p=0.009) are significant independent factors for increasing the risk of drugs discontinuation due to the development of AEs. The type of bDMARDs/tsDMARD used also significantly correlated with the risk of discontinuation of therapy due to AEs. A relatively high risk of treatment discontinuation was observed with infliximab (IFN) and certolizumab pegol (CZP). Cancellation of IFN was associated with the occurrence of infusion reactions and infectious complications, and CZP was associated with infectious complications.Conclusion. An increase in the dose of MT and decrease in the use of GCs can help prevent the development of AEs leading to the abolition of biologics and tsDMARDs. Significant differences were found between bDMARDs in terms of the risk of their cancellation due to AEs.

Immune-Mediated Diseases Following COVID-19 Vaccination: Report of a Teaching Hospital-Based Case-Series.

The occurrence and course of immune-mediated diseases (IMDs) following COVID-19 vaccination has been little explored so far. We retrieved, among adult patients hospitalized at the Internal Department of a French university hospital up to May 2022, all those who had developed, or relapsed to, an IMD less than 3 weeks following COVID-19 vaccination, without other triggers. Twenty-seven (24 new-onset) post-COVID-19 vaccine IMDs were recorded. They comprised giant cell arteritis or polymyalgia rheumatica (n = 16, HLA-DRB1*04 in 58% of 12 assessed GCA cases), immune-mediated necrotizing myositis or acute rhabdomyolysis, systemic vasculitis, immune thrombocytopenic purpura, rheumatoid arthritis, anti-synthetase syndrome, and adult-onset Still's disease. The causative vaccines were mRNA-based (20 cases) or viral vector-based (7 cases). The IMD typically occurred after the first vaccine dose, with an average delay of 8 (5 SD) days. The patients' mean age was 67 years, and 58% were women. The IMDs had protracted courses in all but three of the patients and typically required high-dose glucocorticoids, in combination with immunomodulators in 13 patients. One patient died of intractable rhabdomyolysis, whereas five suffered permanent damage from IMDs. Eleven patients with well-controlled IMDs completed their COVID-19 vaccination schedule, and two suffered mild IMD relapses. There is a risk of IMDs, notably GCA/PMR, and muscle disorders, following COVID-19 vaccination. Such adverse reactions typically occurred after the first dose, raising concern about subsequent COVID-19 vaccinations. However, early re-challenge in well-controlled IMDs appeared safe.