Expert Review of Clinical Immunology最新文献

Introduction: Extracorporeal Photopheresis (ECP) may be considered the unique large-scale cell therapy currently available. It is currently employed mainly as second-line treatment, especially in steroid-resistant or steroid-dependent Graft versus Host Disease (GvHD) with good results and very few limitations.

Areas covered: Many points need to be clarified regarding the ECP mechanism of action, that conditions the lack of uniqueness among the different centers, essentially cycle frequency, treatment duration, and the number of cells to be treated to obtain a response, according to the organs involved. Moreover, reliable biomarkers for prediction of response are lacking, as well as the best pharmacological combination. We will focus on the recent advances concerning ECP for GvHD treatment. We performed a systematic literature research in Pubmed and Embase as of September 2023.

Expert opinion: The recent studies on ECP mechanism of action along with the promising biomarkers of response, and the synergistic benefit of ECP in association with the new drugs render this therapy an important weapon for GvHD resistant to conventional treatment and can be proposed as a valid first-line therapy option with promising results. We believe that it should be used early in all categories of patients, considering its high safety profile.

Introduction: Metabolic-associated liver diseases have emerged pandemically across the globe and are clinically related to metabolic disorders such as obesity and type 2 diabetes. The new nomenclature and definition (i.e. metabolic dysfunction-associated steatotic liver disease - MASLD; metabolic dysfunction-associated steatohepatitis - MASH) reflect the nature of these complex systemic disorders, which are characterized by inflammation, gut dysbiosis and metabolic dysregulation. In this review, we summarize recent advantages in understanding the pathophysiology of MASLD, which we parallel to emerging therapeutic concepts.

Areas covered: We summarize the pathophysiologic concepts of MASLD and its transition to MASH and subsequent advanced sequelae of diseases. Furthermore, we highlight how dietary constituents, microbes and associated metabolites, metabolic perturbations, and immune dysregulation fuel lipotoxicity, hepatic inflammation, liver injury, insulin resistance, and systemic inflammation. Deciphering the intricate pathophysiologic processes that contribute to the development and progression of MASLD is essential to develop targeted therapeutic approaches to combat this escalating burden for health-care systems.

Expert opinion: The rapidly increasing prevalence of metabolic dysfunction-associated steatotic liver disease challenges health-care systems worldwide. Understanding pathophysiologic traits is crucial to improve the prevention and treatment of this disorder and to slow progression into advanced sequelae such as cirrhosis and hepatocellular carcinoma.

Background: The only causal treatment for allergic rhinitis (AR) is allergen immunotherapy (AIT) including personalized liquid sublingual AIT (SLIT). We present the methodology for establishing the EfficAPSI cohort to further evaluate the real-life effectiveness and use of SLIT liquid.

Research design and methods: The EfficAPSI cohort was constituted by deterministic linkage of Stallergenes Greer dispensing and nationwide French healthcare insurance system (SNDS) databases. Data from 2006 to 2018 were extracted. All patients who initiated Stallergenes Greer SLIT liquid between 2010 and 2013 were considered as exposed and those dispensed with AR symptomatic treatment only as control. To limit the impact of confounding, the models will be weighted using the inverse probability of treatment weighting (IPTW).

Results: A total of 445,574 patients were included; median age was 38 years; 59.1% were female. Exposed patients (n = 112,492) were significantly younger, more frequently males, and less likely to have comorbidities than controls (n = 333,082). After IPTW, patients' characteristics from both groups were similar.

Conclusions: To date, the EfficAPSI cohort has the largest number of person-years of follow-up in the field of AIT. The completeness of the data allows to evaluate SLIT liquid effectiveness with rigorous methodology, leading to important insights on personalized medicine in real-life.

Introduction: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose.

Areas covered: We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence.

Expert opinion: HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5-2.5 mg/day be never exceeded in long-term maintenance treatments.

Introduction: The management of refractory juvenile idiopathic associated uveitis (JIAU) or childhood-onset chronic anterior uveitis (CAU) is a challenge. There is no clear consensus or evidence base for to suggest the most appropriate therapy after primary or secondary failure of biweekly adalimumab. In this scenario, most clinicians advocate switching to another anti-tumor necrosis factor alpha inhibitor; however, there are a variety of other disease modifying agents to choose from albeit with a differing levels of evidence.

Areas covered: We discuss how to define nonresponse and potential treatment options for patients with JIAU and CAU refractory to biweekly adalimumab.

Expert opinion: Uncontrolled CAU and JIAU remain one of the most challenging diseases to manage and can lead to irreversible loss of vision in a third of those affected. Amongst the possible choices, weekly adalimumab, infliximab, tocilizumab and abatacept have more evidence to support their use. JAK inhibitors seem to be a promising option. Golimumab and Rituximab has also been thought to be partially effective in some refractory cases, whereas IL-17, IL-23, and IL-12 inhibition along with apremilast seem not to be a therapeutic option currently. The route of administration should also be considered as there can be significant pros and cons for different children.