Safety considerations when treating myelofibrosis

O’Sullivan, Jennifer; McLornan, Donal; Harrison, Claire

doi:10.1080/14740338.2016.1185414

Cited by 9 publications

(8 citation statements)

References 76 publications

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“…38,39 Dose-limiting myelosuppression, particularly in the first 3 months of therapy, was common. Increased risk for infection has been documented, ranging from common bacterial/viral ailments to rare severe infections such as progressive multifocal leukoencephalopathy (reviewed in O'Sullivan et al 40 )…”

Section: Jak Inhibition Targeted Therapy For Mpnmentioning

confidence: 99%

Emerging treatments for classical myeloproliferative neoplasms

Vannucchi

Harrison

2017

Blood

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There has been a major revolution in the management of patients with myeloproliferative neoplasms (MPN), and in particular those with myelofibrosis and extensive splenomegaly and symptomatic burden, after the introduction of the JAK1 and JAK2 inhibitor ruxolitinib. The drug also has been approved as second-line therapy for polycythemia vera (PV). However, the therapeutic armamentarium for MPN is still largely inadequate for coping with patients’ major unmet needs, which include normalization of life span (myelofibrosis and some patients with PV), reduction of cardiovascular complications (mainly PV and essential thrombocythemia), prevention of hematological progression, and improved quality of life (all MPN). In fact, none of the available drugs has shown clear evidence of disease-modifying activity, even if some patients treated with interferon and ruxolitinib showed reduction of mutated allele burden, and ruxolitinib might extend survival of patients with higher-risk myelofibrosis. Raised awareness of the molecular abnormalities and cellular pathways involved in the pathogenesis of MPN is facilitating the development of clinical trials with novel target drugs, either alone or in combination with ruxolitinib. Although for most of these molecules a convincing preclinical rationale was provided, the results of early phase 1 and 2 clinical trials have been quite disappointing to date, and toxicities sometimes have been limiting. In this review, we critically illustrate the current landscape of novel therapies that are under evaluation for patients with MPN on the basis of current guidelines, patient risk stratification criteria, and previous experience, looking ahead to the chance of a cure for these disorders.

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Section: Jak Inhibition Targeted Therapy For Mpnmentioning

confidence: 99%

Emerging treatments for classical myeloproliferative neoplasms

Vannucchi

Harrison

2017

Blood

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“…Safety data for tofacitinib is derived from large clinical trials in RA and psoriasis 42–45 , and data for ruxolitinib are from clinical trials in myelofibrosis and polycythemia vera 46–48 .…”

Section: Safety Datamentioning

confidence: 99%

“…With ruxolitinib, the most common infection was urinary tract infection 46,48 . With both tofacitinib and ruxolitinib, there is increased risk of varicella zoster virus reactivation 46,48,49 , usually limited to localized disease. Impaired response to vaccination has been reported with tofacitinib and is theoretically a risk with ruxolitnib, too.…”

Section: Safety Datamentioning

confidence: 99%

JAK inhibitors in dermatology: The promise of a new drug class

Damsky

King

2017

Journal of the American Academy of Dermatology

397

286

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New molecularly targeted therapeutics are changing dermatologic therapy. JAK-STAT is an intracellular signaling pathway upon which many different pro-inflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors may be a useful therapeutic strategy for these diseases. There is growing evidence that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition may be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

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“…Most data for oral JAK inhibitors are from their use for other indications. Data from larger clinical trials with ruxolitinib for polycythemia and myelofibrosis have noted UTI's to be the most common adverse event 47–53 with an increased risk of herpes zoster 47–54 . Anemia was more commonly observed with ruxolitinib due to its greater JAK2 inhibition 54 .…”

Section: Safety Data and Adverse Eventsmentioning

confidence: 99%

Alopecia areata—New updates with long‐term use of JAK inhibitors

Nguyen

Mesinkovska

2021

Dermatological Reviews

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Alopecia areata (AA) is an autoimmune condition of multifactorial etiology that affects about 2% of the general population. It is a disease leading to significant emotional and psychosocial distress. There are very limited treatment options available for AA with no therapy demonstrating sustained remission long term. Understanding the genetic and molecular mechanisms of AA have led to the development of novel molecularly targeted treatments such as the Janus Kinase (JAK) inhibitors. Evidence suggests that JAK inhibitors may be broadly useful in dermatology with promising developments in open‐label clinical trials for AA. Here, the results of long‐term use of JAK inhibitors are reviewed and discussed for moderate‐to‐severe AA.

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Safety considerations when treating myelofibrosis

Cited by 9 publications

References 76 publications

Emerging treatments for classical myeloproliferative neoplasms

Emerging treatments for classical myeloproliferative neoplasms

JAK inhibitors in dermatology: The promise of a new drug class

Alopecia areata—New updates with long‐term use of JAK inhibitors

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