Ruxolitinib for treatment of steroid-refractory graft-versus-host disease in adults: a systematic review and meta-analysis

Li, Hui; Li, Qi; Hu, Guoyu; Shen, Xu-Liang; Tan, Meiao

doi:10.1080/17474086.2020.1738214

Cited by 18 publications

(16 citation statements)

References 42 publications

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“…Janus kinase 1 (JAK1) and JAK2 are known to transduce IFN-γ signaling ( 43 ). Inhibitors of JAK1 and JAK2 such as ruxolitinib effectively disrupt this pathway and are used clinically to treat patients with myelofibrosis ( 44 ) and graft-versus-host disease ( 45 ). We observed strong inhibition of IFN-γ–induced SLAMF7 expression in macrophages treated with ruxolitinib in vitro (Fig.…”

Section: Resultsmentioning

confidence: 99%

SLAMF7 engagement superactivates macrophages in acute and chronic inflammation

et al. 2022

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Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a superactivated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression and engaging SLAMF7 drove a strong wave of inflammatory cytokine expression. Induction of TNF-α after SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients but also in gut macrophages from patients with active Crohn’s disease and in lung macrophages from patients with severe COVID-19. This suggests a central role for SLAMF7 in macrophage superactivation with broad implications in human disease pathology.

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Section: Resultsmentioning

confidence: 99%

SLAMF7 engagement superactivates macrophages in acute and chronic inflammation

et al. 2022

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“…Cytopenias occurred in half of cases, peripheral edema in 45 %, but no significant infective toxicity has been reported [46]. In another cohort, Ruxolitinib, at a dose of 20 mg/day, offered 57.1 % of ORR; reported adverse events were anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and transaminitis [47]. In the cGVHD, Ruxolitinib has been reported to be effective in 80 % of patients; nevertheless, reactivation of CMV occurred in 15 % of patients [48].…”

Section: Jak2 Inhibitorsmentioning

confidence: 96%

“…In the cGVHD, Ruxolitinib has been reported to be effective in 80 % of patients; nevertheless, reactivation of CMV occurred in 15 % of patients [48]. In a meta-analysis including 414 patients with cGVHD, during treatment with Ruxolitinib infections occurred in 20 % of patients, more frequently sustained by bacteria (55 %) and CMV (39 %) [49]. The proinfective aspect of Ruxolitinib is also evident in myelofibrosis, where cases of hepatitis B [50] and tuberculosis (in 1.4 % of cases) [51] reactivation, in addition to pneumonitis sustained by Pneumocystis jiroveci [52], have been reported.…”

Section: Jak2 Inhibitorsmentioning

confidence: 99%

The CoV-2 outbreak: how hematologists could help to fight Covid-19

Galimberti

Baldini

Baratè³

et al. 2020

Pharmacological Research

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COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in the light of their possible application in COVID-19. The most promising drugs might be: Ruxolitinib, a JAK1/2 inhibitor, with a rapid and powerful anticytokine effect, tyrosine kinase inhibitors (TKIs), with their good anti-inflammatory properties, and perhaps the anti-Cd26 antibody Begelomab. We also present immunological data from gene expression experiments where TKIs resulted effective anti-inflammatory and pro-immune drugs. A possible combined treatment algorithm for COVID-19 is here proposed.

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“…JAK1 and JAK2 are known to transduce IFN-γ signaling ( 41 ). Inhibitors of JAK1 and JAK2 such as ruxolitinib effectively disrupt this pathway and are used clinically to treat patients with myelofibrosis ( 42 ) and graft versus host disease ( 43 ). We observed profound inhibition of IFN-γ induced SLAMF7 expression in macrophages treated with ruxolitinib in vitro (Fig.…”

Section: Resultsmentioning

confidence: 99%

SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

Simmons

Nguyen

Gomez-Rivas

et al. 2020

Preprint

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Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-gamma as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-alpha following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn's disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.

show abstract

Ruxolitinib for treatment of steroid-refractory graft-versus-host disease in adults: a systematic review and meta-analysis

Cited by 18 publications

References 42 publications

SLAMF7 engagement superactivates macrophages in acute and chronic inflammation

SLAMF7 engagement superactivates macrophages in acute and chronic inflammation

The CoV-2 outbreak: how hematologists could help to fight Covid-19

SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

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