Ruxolitinib treatment permits lower cumulative glucocorticoid dosing in children with secondary hemophagocytic lymphohistiocytosis

Chen, Ying; Liang, Rong; Zhou, Zixiang; Shi, Xiaodong; Ding, Yuchuan; Li, Jianguo

doi:10.1186/s12969-021-00534-0

Cited by 8 publications

(11 citation statements)

References 45 publications

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“…As the favorable response to ruxolitinib in HLH ( 6 , 15 ), three patients with SJIA-MAS showed a good response within 1 week after introducing this agent. One patient showed a partial response with residual manifestations of intermittent skin rash and hyperferritinemia.…”

Section: Discussionmentioning

confidence: 92%

“…Ruxolitinib, as a JAK 1 and 2 inhibitor, has been tested in mouse models of hemophagocytic lymphohistiocytosis (HLH) and found to promote survival and reduce levels of proinflammatory cytokines IL-6 and TNF-α ( 4 , 5 ). Ruxolitinib helped to control disease activity and reduce the cumulative dose of glucocorticoids in children with secondary hemophagocytic lymphohistiocytosis ( 6 ). Ruxolitinib combined with the doxorubicin–etoposide–methylprednisolone (Ru-DEP) regimen may be a safe and effective salvage therapy for refractory/relapsed HLH, especially MAS ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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JAK inhibitors in systemic juvenile idiopathic arthritis

Xia

Luo

et al. 2023

Front. Pediatr.

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ObjectiveSystemic juvenile idiopathic arthritis (SJIA) is characterized by excessive and inappropriate production of proinflammatory cytokines. Janus kinase inhibitors (JAKi) can block the downstream pathway of many cytokines. The use of JAKi in SJIA or macrophage activation syndrome (MAS) has only been described in a limited number of case reports. In this study, we aimed to assess the efficacy and potential adverse effects of JAKi in SJIA patients.MethodsPatients with SJIA who received JAKi and underwent at least one assessment of efficacy and safety after JAKi initiation were eligible for this study. Data were collected retrospectively from inpatient or outpatient medical records at JAKi initiation, at 1, 3, 6, 9, and 12 months, after disease flare, after JAKi discontinuation, or at the last follow-up.ResultsTen patients with SJIA were included in the study. At the start of JAKi treatment, all patients presented with active disease; five showed variable adverse effects secondary to glucocorticoids. Seven patients received tofacitinib (one later switched to ruxolitinib). Of these, only two patients showed a complete response of persistent arthritis associated with tocilizumab; tofacitinib was used without a biological DMARD only in two patients, together with MTX, showing a partial response; three patients were nonresponders. Four patients with SJIA-related MAS or persistent hyperferritinemia were treated with ruxolitinib. Ruxolitinib allowed a good response on MAS parameters in three of them. All these four patients required an adjunction or switch to canakinumab later. The median decrease in the daily glucocorticoid dose between JAKi initiation and the last follow-up was 90.6% in patients with complete remission and 77.4% in other patients. Three patients discontinued glucocorticoid treatment after the introduction of JAKi. Severe adverse events, notably serious infection or thrombosis, were not observed during JAKi treatment.ConclusionJAKi may be an alternative or adjuvant agent for SJIA patients, especially in those with persistently active disease, glucocorticoid-related adverse reactions, or SJIA-MAS.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

JAK inhibitors in systemic juvenile idiopathic arthritis

Xia

Luo

et al. 2023

Front. Pediatr.

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“…Pulsed methylprednisolone is an alternative. 72 In view of the significant side effects of corticosteroids, steroid-sparing agents are usually added on following the initial management of these inflammatory conditions to spare the use of steroids and minimize their side effects.…”

Section: Methodsmentioning

confidence: 99%

“…The unusual dosage is 1 mg/kg daily for 2 days, or 0.5 mg/kg/day for 5 days. 49 , 72 , 73 If the fever does not respond to the above dosage schedule, an additional dose may be considered. 73 When administered in the first 10 days of the disease, IVIG reduces the risk of coronary artery damage in patients without serious side effects.…”

Section: Methodsmentioning

confidence: 99%

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Drugs for paediatric hyperinflammatory syndromes

Hon¹,

Leung²,

Leung³

et al. 2022

DIC

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Background Many syndromes are associated with exaggerated inflammation. Children with hyperinflammatory syndromes often present with vague and non-specific symptoms that pose diagnostic and management challenges. The recent literature seems biased towards referring these syndromes only to the multisystem inflammatory syndrome in children (MIS-C) that is associated with COVID-19. The purpose of this paper is to provide an updated narrative review on the pathophysiology, manifestations and management approaches for common hyperinflammatory syndromes. Methods An extensive PubMed search of all publications in the English literature was performed with Clinical Queries for various hyperinflammatory syndromes and conditions using the undermentioned Medical Subject Headings: “hyperinflammation”, “hyperinflammatory syndromes”, “sepsis syndrome”, “severe inflammatory response syndrome” and “acute respiratory distress syndrome”. Categories were limited to reviews and clinical trials for the age range from birth to 18 years. Results The criteria, presentation and management of these hyperinflammatory syndromes are described. Hyperinflammatory syndromes refer to a basket of inflammatory syndromes often associated with multisystem involvement and aberrant cytokine release and should be differentiated from autoinflammatory, autoimmune and hyperimmune syndromes. The major subtypes of hyperinflammatory syndromes, including macrophage activation syndrome, haemophagocytic lymphohistiocytosis, cytokine release syndrome and cytokine storm syndrome, are described. MIS-C associated with SARS-CoV-2 represents the latest addition. It must be understood that the syndrome is not exclusive to COVID-19 but could be caused by various viral infections. Early recognition, prompt and proactive treatment can reduce potential complications and improve outcomes and survival rates in paediatric patients. Anti-inflammatory medications for the management of these syndromes are described. Conclusion The incidence of these hyperinflammatory conditions is generally low in comparison to other disease conditions. Except for paediatric inflammatory multisystem syndrome/MIS-C, the mortality is high and the hospital stay is prolonged in affected patients. Acute and critical care physicians must be aware of these conditions and their initial management. Corticosteroids are often used in the initial phrase but various disease-specific drugs and biologics are needed in subsequent management and expert management of these often-difficult conditions is crucial.

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