Bilateral Toxoplasmosis Retinitis Associated with Ruxolitinib

Goldberg, Roger A.; Reichel, Elias; Oshry, Lauren

doi:10.1056/nejmc1302895

Cited by 86 publications

(56 citation statements)

References 5 publications

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“…The observation that the therapeutic effects are irrespective of the patients' JAK mutational status and that the compound induces only limited anticlonal activity (6) suggests that it profoundly modifies the inflammatory microenvironment. The idea that JAK inhibitors are immunosuppressive is underscored by an increased infection rate of patients treated with ruxolitinib (7)(8)(9)(10)(11), but also by its potential benefit in inflammatory-driven cancers, such as pancreatic cancer with increased C-reactive protein levels (12). In line with these clinical observations, we recently provided evidence that JAK inhibitors markedly impair dendritic cell biology (13).…”

Section: Introductionsupporting

confidence: 67%

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

et al. 2015

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Ruxolitinib is a small-molecule inhibitor of the JAK kinases, which has been approved for the treatment of myelofibrosis, a rare myeloproliferative neoplasm (MPN), but clinical trials are also being conducted in inflammatory-driven solid tumors. Increased infection rates have been reported in ruxolitinib-treated patients, and natural killer (NK) cells are immune effector cells known to eliminate both virus-infected and malignant cells. On this basis, we sought to compare the effects of JAK inhibition on human NK cells in a cohort of 28 MPN patients with or without ruxolitinib treatment and 24 healthy individuals. NK cell analyses included cell frequency, receptor expression, proliferation, immune synapse formation, and cytokine signaling. We found a reduction in NK cell numbers in ruxolitinib-treated patients that was linked to the appearance of clinically relevant infections. This reduction was likely due to impaired maturation of NK cells, as reflected by an increased ratio in immature to mature NK cells. Notably, the endogenous functional defect of NK cells in MPN was further aggravated by ruxolitinib treatment. In vitro data paralleled these in vivo results, showing a reduction in cytokine-induced NK cell activation. Further, reduced killing activity was associated with an impaired capacity to form lytic synapses with NK target cells. Taken together, our findings offer compelling evidence that ruxolitinib impairs NK cell function in MPN patients, offering an explanation for increased infection rates and possible longterm side effects associated with ruxolitinib treatment. Cancer Res; 75(11);

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Section: Introductionsupporting

confidence: 67%

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

et al. 2015

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“…3,4 This phenomenon narrows the candidacy of the large number of variants that are generated by next-generation sequencing, which makes it possible to identify the causal mutation even in simplex cases. 5,6 Thus, the study of unclassified IBMFSs in Saudi Arabia where the consanguinity rate is high represents an opportunity to identify novel disease genes, and these may similarly contribute to the causation of IBMFSs in outbred populations. We implemented this approach in 2 siblings with an apparently novel IBMFS and identified a homozygous truncating mutation in the MYSM1 gene encoding MYB-like, SWIRM, and MPN domainscontaining protein 1.…”

Section: And Cd8mentioning

confidence: 99%

Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis?

Heine

Brossart

Wolf

2013

Blood

143

109

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“…Recently, a series of case reports identified a potential association between ruxolitinib therapy and the development of severe infections, such as disseminated tuberculosis (2), Cryptococcus neoformans pneumonia (3) and bilateral toxoplasmosis retinitis (4). Additionally, two groups reported a patient with myelofibrosis who experienced a reactivation of hepatitis B virus after ruxolitinib treatment (5,6).…”

Section: Introductionmentioning

confidence: 99%

Elevation of the Hepatitis B Virus DNA during the Treatment of Polycythemia Vera with the JAK Kinase Inhibitor Ruxolitinib

2016

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Ruxolitinib is a useful treatment option for myelofibrosis since it effectively resolves splenomegaly and constitutional symptoms. After the widespread use of ruxolitinib outside of clinical trials, a series of case reports indicated a potential risk of ruxolitinib-associated opportunistic infections, including the reactivation of the hepatitis B virus (HBV). We herein report the case of a polycythemia vera patient who showed an elevation of HBV-DNA viral DNA with an elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after the initiation of ruxolitinib. Anti-viral therapy with entecavir was immediately started and the HBV viral load thereafter decreased with an improvement of the liver function. Physicians should thus be aware of the potential risk of ruxolitinib-associated HBV reactivation.

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Bilateral Toxoplasmosis Retinitis Associated with Ruxolitinib

Cited by 86 publications

References 5 publications

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis?

Elevation of the Hepatitis B Virus DNA during the Treatment of Polycythemia Vera with the JAK Kinase Inhibitor Ruxolitinib

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