Cumulative Glucocorticoid Dose Research Articles

Off-label use of mycophenolate mofetil in immune-mediated diseases

Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

Advantages of an alternate-day glucocorticoid treatment strategy for the treatment of IgG4-related disease: A preliminary retrospective cohort study.

Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD).Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke’s International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan–Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control.Among the 67 patients with IgG4-RD, patients with alternate-day (n = 13) and daily (n = 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60–70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; P = .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: −29.5 [−54.3, −4.8], P = .021 at 12 months; −20.0 [−39.8, −0.1], P = .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], P = .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; P = .43).The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.

Bone remodeling serum markers in children with systemic lupus erythematosus

IndroductionSLE is an autoimmune multisystem disease. Glucocorticoid is an irreplaceable medication for SLE. Glucocorticoid and inflammatory mediators impact bone remodeling by OPG/RANKL/RANK signal system, which could lead to osteoporosis. Our aim is to detect the expression of RANKL/OPG in children with SLE, and to preliminarily explore the changes of bone remodeling serum markers in children with SLE.MethodsSerum RANKL and OPG of 40 children with SLE and healthy children were detected by ELISA, while 25(OH)VitD3 was detected routinely. Clinical data of children with SLE were recorded, including gender, age, height, weight, BMI, SLEDAI, duration of the disease, cumulative dose of glucocorticoid, and correlation analysis was conducted with RANKL, OPG and 25(OH)VitD3.ResultsSerum RANKL concentrations in SLE group were significantly higher than health group (9.82 ± 7.20 vs. 6.80 ± 4.35 pg/ml and 0.081 ± 0.072 vs. 0.042 ± 0.034, P < 0.05) respectively, and the concentrations of OPG and 25(OH)VitD3 in serum were significantly lower than health group (156.34 ± 57.33 vs. 189.16 ± 68.70 pg/ml and 43.66 ± 31.27 vs. 59.04 ± 21.56 mmol/L, P < 0.05). Serum RANKL in children with SLE was positively correlated with the duration of SLE, cumulative dose of GC(r = 0.593, 0.727, P < 0.05). And it was negatively correlated with serum OPG and 25(OH)VitD3 (r = -0.601, -0.469, P < 0.05). In addition, serum OPG and 25(OH)VitD3 concentrations were inversely correlated with cumulative dose of GC (r = -0.66, -0.508, P < 0.05).ConclusionLow levels of vitamin D3 and bone metabolic abnormalities still persist in children with SLE even if the disease is in remission, while serum RANKL level was elevated, OPG expression was reduced. In the case of disease remission, GC is involved in the occurrence and development of abnormal bone remodeling through RANKL/OPG.

Association of nesfatin-1 levels and bone remodeling markers in patients with rheumatoid arthritis

Aim. To evaluate the association of nesfatin-1 (NF-1) levels and bone remodeling markers in patients with rheumatoid arthritis (RA).Materials and methods. 110 patients (105 women and 5 men) with RA, classified by ACR/EULAR 2010 criteria were enrolled in our study. All patients undergone complete clinical and laboratory examination. NF-1 serum levels were determined using a commercial test-systems (RayBio® Nesfatin Enzyme Immunoassay [EIA] Kit). Statistical analysis was performed using a software package Statistica 12.0. The results were considered statistically significant at p &lt; 0.050.Results. Significant positive correlation was determined between serum NF-1 levels and Intact N-Terminal Propeptide of Type 1 Procollagen (P1NP) levels (r = 0.218; p = 0.022). Serum NF-1 levels were not associated with bone mineral density in lumbar spine and femur. Serum NF-1 levels didn't correlate with body composition indices and Beta-CrossLaps levels. Patients with osteoporosis (n = 53) and osteoporotic fractures (n = 25) had statistically significant higher levels of NF-1 (Z = –2.060; p = 0.040 и Z = –2.370; p = 0.017 respectively). However, serum NF-1 levels didn’t correlate with cumulative dose of glucocorticoids (ρ = 0.090; p = 0.368) and the duration of glucocorticoids intake (ρ = 0.070; p = 0.462).Conclusions. In our study, we determined the significant positive correlation between NF-1 and P1NP levels, supposingly due to NF-1 possible effect on the osteoblasts differentiation and function. Patients with osteoporosis and osteoporotic fractures had higher median blood serum levels of NF-1.

The frequency of sarcopenia and factors affecting appendicular muscle mass in patients with systemic sclerosis

Aim. To determine the frequency of sarcopenia (SP) and to identify factors associated with the muscle mass in women with systemic sclerosis (SSc).Materials and methods. The study included 64 women with SSc aged 40–70 years. Questionnaires, clinical, instrumental, laboratory examinations and absorptiometry. Linear regression analysis was performed to identify factors associat ed with appendicular muscle mass (AMM).Results. Probable SP was detected in 35 (54.7 %), and confirmed SP – 17 (26.5 %) women with SSc. The frequency of SP did not differ depending on the form of the disease. Univariate linear analysis revealed the relationship between the AMM and BMI, nutritional status; mid-upper arm, waist, hip and calf circumferences, skin Rodnan score, cumulative dose of glucocorticoids (GC) and BMD of the proximal hip. Multivariate linear analysis confirmed the presence of associations between the AMM index and BMI (b = 0.65; p &lt;0.001), the Rodnan skin score (b = –0.19; p = 0.047), the cumulative dose of GC (b = –0.22; p = 0.021).Conclusion. The study demonstrated that more than a quarter of patients with SSc had a confirmed SP. Although age is the main risk factor for SP in the general population, in our study it did not differ between patients with low and normal AMM. The cumulative dose of GC and the Rodnan skin score were negatively, and BMI was positively associated with the value of AMМ.

Clinical Study on Systemic Lupus Erythematosus Complicated with Knee Bone Infarction.

Objective The present study aims to (1) analyze the clinical characteristics and related influencing factors of knee bone infarction in systemic lupus erythematosus (SLE) and (2) improve the understanding of SLE complicated with knee bone infarction. Methods The data of patients with SLE complicated with knee bone infarction were retrospectively analysed; patients with SLE during the same period who matched in age, gender, and disease duration were selected as control subjects, with a 1 : 1 ratio with the SLE group. The clinical data were collected to analyze the risk factors for SLE complicated with knee bone infarction. Results In a total of 36 (6.4%) of 563 patients aged 19–33 (25.8 ± 4.8) years who had SLE during the same period, the disease was complicated with knee bone infarction. The diagnosis of knee bone infarction was made at an SLE duration of 7–65 (26.2 ± 15.7) months. During the SLE course, knee bone infarction occurred within 1 year in 6 cases (16.7%), within 1–5 years in 28 cases (77.8%), and in >5 years in 2 cases (5.6%). Raynaud's phenomenon incidence and anti-nRNP antibody positivity were significantly higher in the knee bone infarction group than in the control group (P < 0.01 and P < 0.05, respectively). The cumulative glucocorticoid dose at 1, 3, and 6 months was significantly higher in the knee bone infarction group than in the control group (P < 0.05). SLE complicated with knee necrosis had a statistically significant rank correlation with Raynaud's phenomenon (r = 0.445, P < 0.001), anti-nRNP antibody (r = 0.309, P=0.008), and renal injury (r = 0.252, P=0.032). The multivariate analysis of SLE complicated with knee bone infarction showed that Raynaud's phenomenon was an independent influencing factor for the complicated knee bone infarction in SLE patients (OR = 4.938, P=0.004), and the probability of SLE complicated with knee bone infarction in Raynaud's phenomenon positive patients was 4.938 times that of Raynaud's phenomenon negative patients. Conclusions The risk of knee bone infarction was relatively high in patients with SLE within a 5-year disease course and in young patients. The risk factors were Raynaud's phenomenon, anti-nRNP antibody positivity, and early high-dose glucocorticoid therapy.

Factors affecting bone mineral density in children and adolescents with secondary osteoporosis.

This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. We retrospectively reviewed the medical records of patients aged 10-18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P&gt;0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Retroperitoneal fibrosis - diagnosis and treatment.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, often with nocturnal exacerbations and not responding to position changes. The disease is commonly associated with signs of systemic inflammatory response (malaise, fever, and anorexia and weight loss). Glucocorticoids are considered the cornerstone of the therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab have been reported as a valuable option mostly in case reports, cases series and small studies. These agents allowed to reduce cumulative dose of glucocorticoids and their adverse effects. Combined therapy is preferable for all patients who suffer from significant glucocorticoid- related toxicity or in cases where glucocorticoids alone are insufficient to treat the condition.

Patients' Baseline Characteristics, but Not Tocilizumab Exposure, Affect Severe Outcomes Onset in Giant Cell Arteritis: A Real-World Study.

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05–5.55], p = 0.039; HR, 2.08 [1.14–3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.

Medium Versus High Initial Prednisone Dose for Remission Induction in Lupus Nephritis: A Propensity Score-Matched Analysis.

The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3-1.0 mg/kg/day. However, recent studies reported noninferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30 mg/day or ≥40 mg/day. Patients with new-onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30 mg/day) and high prednisone groups (≥40 mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria <0.5 gm/day and no worsening in renal function. Glucocorticoid-related damage was also assessed. High-dose prednisone patients (n = 103; mean ± SD dose 48.6 ± 12.3 mg/day) achieved better rates of complete response compared to the medium group (n = 103; mean ± SD dose 24.2 ± 4.6 mg/day) (61.8% versus 38.2%; P = 0.024) at 12 months. The difference in response rates was reproduced for several subgroups (concomitant immunosuppressive treatment, proliferative/nonproliferative LN). Complete remission rates were higher at 2 years (67.8% versus 39%; P = 0.002) and 3 years (64.9% versus 49.1%; P = 0.025) after LN diagnosis. Cumulative glucocorticoid dose was comparable at 2 and 3 years. Glucocorticoid-related damage was accelerated in both groups for the same period. Higher initial prednisone doses (median 45 mg/day) achieved significantly better rates of complete renal response at 12 months in new-onset LN. Cumulative glucocorticoid dose and damage accrual were not different at 2 and 3 years after LN. Damage was more prominent in the late phases of LN in both groups, underlining the importance of rapid tapering and the need to implement alternative strategies.

Long-term use of glucocorticoids for polymyalgia rheumatica: follow-up of the PMR Cohort Study.

ObjectivesPMR is a common inflammatory condition in older adults, characterized by bilateral hip and shoulder pain and stiffness. Reducing oral glucocorticoids, classically used for ≤2 years, are the mainstay of treatment. This study considers the factors early in the disease course that might be associated with prolonged treatment.MethodsSix hundred and fifty-two people with incident PMR were recruited from English general practices (2012–2014). Participants completed seven questionnaires over 2 years (used to allocate people to pain–stiffness trajectories) and a further long-term follow-up (LTFU) questionnaire a median of 5.16 years after diagnosis. Characteristics of those still taking and having ceased glucocorticoids were described and compared using Kruskal–Wallis and χ2 and Student’s 2-sample t-tests as appropriate.ResultsOf the 197 people completing the LTFUQ questionnaire, 179 people reported ever having taken glucocorticoids. Of these, 40.1% were still on treatment, with a median (quartile 1, quartile 3) daily dose of 5 (1.5, 9) mg. People still taking glucocorticoids were more likely to be older (72.5 vs 70.2 years, P = 0.035), live alone (31.8 vs 15.0%, P = 0.01) and have self-managed their glucocorticoid dose (39.1 vs 11.0%, P < 0.0001). They were also more likely to belong to a pain–stiffness trajectory class with sustained symptoms.ConclusionsPMR is not always a time-limited condition. Few patient characteristics are associated with prolonged treatment early in the disease course, but those who are older and who have sustained symptoms might be at greater risk. Although accurate prediction is not yet possible, clinicians should monitor people with PMR carefully to manage symptoms and reduce the cumulative glucocorticoid dose.

Pentraxin-3 – a potential biomarker in ANCA-associated vasculitis

Objective The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. Method Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. Results Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (ρ = 0.45, p < 0.001, and ρ = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. Conclusion Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.

Systemic lupus erythematosus diagnosed during hospitalization: Greater baseline disease activity, short-term damage, and death

ObjectivesTo analyze initial and follow-up features of patients with systemic lupus erythematosus (SLE) diagnosed during hospitalization. MethodsRetrospective analysis of medical records: two groups were studied, a) SLE diagnosed during hospitalization (SLEin), b) SLE diagnosed on an outpatient basis (SLEout). Results123 patients were assessed, 87% female, mean age at diagnosis was 34 years and 45 (37%) of them were SLEin. Patients in the SLEin group had a median of 144 days from the onset of symptoms to diagnosis of SLE vs. 287 days in the SLEout group (p = 0.04). Initially, SLEin had an average SLEDAI of 10 vs. 8 in SLEout (p = 0.004) and anti-dsDNA was positive in 71% vs. 53% in SLEout (p = 0.07). Within the first 6 months, the average cumulative glucocorticoid dose was 6493 mg in SLEin patients vs. 3563 mg in SLEout (p < 0.001) and immunosuppressant usage was higher in SLEin: 62% vs. 26% in SLEout (p < 0.001). Within the first year, SLEin’s kidney biopsies showed lupus nephritis III or IV in 31% vs. 12% in SLEout (p = 0.003, log-rank test). Within the first 2 years, 6 SLEin patients died vs. 1 SLEout patient (p = 0.02) and SLEin patients had more damage as measured by SLICC/ACR Damage Index (median 0, range 25%–75% 0–1 vs. median 0, range 25%–75% 0–0 in SLEout; p = 0.04). ConclusionsSLEin are initially more active, require higher doses of glucocorticoids and immunosuppressants, have more significant kidney involvement, and present more damage and greater mortality in the short term.

Advances in the Treatment of Giant Cell Arteritis.

Giant cell arteritis (GCA) is the most common vasculitis among elderly people. The clinical spectrum of the disease is heterogeneous, with a classic/cranial phenotype, and another extracranial or large vessel phenotype as the two more characteristic patterns. Permanent visual loss is the main short-term complication. Glucocorticoids (GC) remain the cornerstone of treatment. However, the percentage of relapses with GC alone is high, and the rate of adverse events affects more than 80% of patients, so it is necessary to have alternative therapeutic options, especially in patients with worse prognostic factors or high comorbidity. MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review.

Association of androgen excess and bone mineral density in women with classical congenital adrenal hyperplasia with 21-hydroxylase deficiency.

This study aims to assess BMD and its association with androgen excess in women with CAH. We enrolled 92 women with CAH with 21-OH deficiency and retrospectively reviewed their clinical features, hormone concentrations, body composition, glucocorticoid (GC) dose, and BMD. BMD was not different according to the subtypes of CAH. BMD at the lumbar spine was lower in women with CAH with regular menstruation than those with irregular menstruation (1.081 vs. 1.165g/cm2, P < 0.05). BMD was lower in women with CAH with 17-hydroxyprogesterone (17-OHP) < 10ng/mL than in those with ≥ 10ng/mL (lumbar spine, 1.019 vs. 1.150g/cm2; femur neck, 0.806 vs. 0.899g/cm2; total hip, 0.795 vs. 0.943g/cm2; all P < 0.05). After adjusting for age and BMI in correlation analyses, testosterone concentrations were positively correlated with lumbar spine, femur neck, and total hip BMD (r = 0.46, r = 0.38, and r = 0.35, respectively; all P < 0.05), while 17-OHP was positively correlated with lumbar spine BMD (r = 0.38, P < 0.01). In subgroup analysis, 17-OHP was positively correlated with BMD (lumbar spine, r = 0.22; femur neck, r = 0.22; total hip, r = 0.24; all P < 0.05) only in the group with a total cumulative dose of GC ≥ 156.0g/m2. Androgen excess may have a protective effect on BMD in women with classic CAH and high cumulative doses of GC.

Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial

BackgroundPolymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing...

Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis.

Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. Results: After a median follow-up duration of 35.6 (2–111) months, the median cumulative GC dose in the 139 patients was 9184 (1770–24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. Conclusion: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.

The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.

Menopause and rheumatoid arthritis as factors associated with osteoporosis development

The aim of the research. To study the role of menopause, glucocorticoids (GCs) intake and characteristics of rheumatoid arthritis (RA) in development of osteoporosis (OP) and osteoporotic fractures. Material and methods. A total of 73 female RA patients in menopause were examined. The control group included 29 female RA patients in premenopause. In addition to standard clinical and laboratory examinations, P1NP, 25(OH)D, CTX-1 were measured, dual-energy x-ray absorptiometry and x-ray of the thoracic and lumbar spine were performed. Statistical analysis was performed using the “Statistica 12.0” software package. Results. Premenopausal patients had lower BMI. Patients in postmenopause had higher rate of OP (42 patients) than the controls (8 patients) (57.5% vs 27.6%, respectively). Among patients in postmenopause, OP was associated with lower BMI (27.6 vs 30.5 kg/m2), higher cumulative dose of GCs (6.9 vs 1.65 g), higher duration of GCs intake (32 vs 18 months), lower RA activity (3.37 vs 3.9 according to DAS28-CRP) and lower CTX-1 level (0.52 vs 0.7 ng/ml). In the same group, osteoporotic fractures were only associated with longer GCs intake (32 vs 24 months). In premenopause patients, OP was associated with longer RA duration (21 vs 6 months), cumulative dose of GCs (13.9 vs 0.45 g), duration of GCs intake (48 vs 3 months), higher level of hs-CRP (46 vs 8 mg/l) and lower P1NP level (51.8 vs 43.8 ng/ml). Osteoporotic fractures in premenopause were associated with RA duration (28 vs 6 months), cumulative dose of GCs (12.5 vs 1.2 g) and lower BMD in all examined areas. Conclusion. The OP rate was higher in postmenopause patients. In both groups, the duration of GCs intake and accumulated dose of GCs were associated with OP. In postmenopause, OP was also associated with lower BMI. In premenopause, OP and osteoporotic fractures were associated with longer RA duration, cumulative dose of GCs and lower BMD in all studied areas.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were...