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Background And Objective: Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases.
Methods: A systematic literature search was conducted in PubMed and Embase for PK/PD studies of systemic corticosteroids in autoimmune and inflammatory diseases in humans published until December 2023. Studies were scored from 1 to 5 according to criteria for the levels of evidence, as inspired by the Oxford Centre for Evidence-Based Medicine.
Results: Twelve studies (1981-2016) were included. The majority of these studies had a small sample size. The corticosteroids involved were prednisone, prednisolone, methylprednisolone and budesonide. Substantial IIV of corticosteroid PK was described in all studies. Evidence for a relationship between the PK of corticosteroids and efficacy was inconclusive and limited. However, there was some evidence for a relationship between the PK of prednisolone and the severity of Cushingoid features.
Conclusion: There is insufficient evidence to draw firm conclusions on the potential associations between PK and clinical outcome of systemic corticosteroid treatment in autoimmune and inflammatory diseases. This is remarkable given the many decades that steroid drugs have been used in clinical care. Prospective research is recommended with robust and well-defined cohorts to fully quantify the PK/PD associations of corticosteroids.
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http://dx.doi.org/10.1007/s40262-024-01419-7 | DOI Listing |
Nature
September 2025
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE). Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 (PLD4). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays.
View Article and Find Full Text PDFNat Rev Immunol
September 2025
St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell-cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is highlighted by the discovery of inborn errors of immunity (IEIs) that are caused by defects in individual actin-regulatory proteins, resulting in immune-related actinopathies. In addition to susceptibility to infection, these often present with a vast array of autoimmune and autoinflammatory manifestations.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
Methods Cell Biol
September 2025
Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVA), Valladolid, Spain. Electronic address:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that is characterized by a severe and progressive demyelinating process. It is considered a neurodegenerative autoimmune disorder driven by immune cell infiltration, overproduction of cytokines and reactive oxygen species (ROS) accumulation that leads to axonal and neuronal injury. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used pre-clinical model of multiple sclerosis (MS), since it resembles many aspects of the human disease.
View Article and Find Full Text PDFPediatr Exerc Sci
September 2025
Division of Movement Science and Exercise Therapy, Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch,South Africa.
Background: Juvenile idiopathic arthritis is an autoimmune condition of multifactorial etiology resulting in chronic inflammatory joint disease, which may be associated with systemic manifestations. Therapeutic exercise is essential to counteract physical impairments, which requires the implementation of outcome measures (OMs) in research and practice as they provide meaningful results for research efficacy, exercise program evaluation and quality, medication tolerance, and patient improvement.
Purpose: To assess the types of OMs implemented in exercise randomized controlled trials related to the juvenile idiopathic arthritis cohort and the psychometric properties and age appropriateness of the implemented OMs.