The dichotomy of glucocorticosteroid treatment in immuneinflammatory rheumatic diseases: an evidence-based perspective and insights from clinical practice

Abstract

ObjectivesGlucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs).Material and methodsThe authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology.ResultsGlucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved.ConclusionsGlucocorticosteroids’ use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

Current Perspectives in Giant Cell Arteritis: Can We Better Connect Pathogenesis and Treatment?

“…On the other hand, GC are well known to induce a series of adverse events like infections, hypertension, diabetes mellitus, osteoporosis and fractures, gastrointestinal bleeding, glaucoma, and cataracts [ 51 ], which should be taken into account, especially in frail patients. One of the earliest and most cited observational studies that evaluated the rate of glucocorticoid-related adverse events [ 52 ] in GCA patients identified that 86% of patients had at least one adverse event, while two or more events occurred in 58% of patients, with the most frequent ones being cataracts, fragility fractures, and infections.…”

Dietary Cholest-4-en-3-one, a Cholesterol Metabolite of Gut Microbiota, Alleviates Hyperlipidemia, Hepatic Cholesterol Accumulation, and Hyperinsulinemia in Obese, Diabetic db/db Mice

“…The steroid group plays a structural role in cell membranes and contributes to physiological functions as a regulator of several important metabolic pathways as secondary messengers and hormones. For example, cortisol and synthetic cortisol-like compounds, termed as corticosteroids, help regulate blood pressure, immune function, and anti-inflammatory processes [ 2 , 3 ]. Moreover, phytosterols and phytostanols (e.g., β-sitosterol, campesterol, sitostanol, campestanol, and saringosterol) have been reported to exert biological effects, including lowering blood low-density lipoprotein cholesterol (LDL-C) levels, improving cognition function, and alleviating the pathology of Alzheimer’s disease [ 4 , 5 , 6 , 7 ].…”