Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis

Martí‐Carvajal, Arturo J; Anand, Vidhu; Solà, Iván

doi:10.1002/14651858.cd010298.pub2

Cited by 36 publications

(25 citation statements)

References 152 publications

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“…Thus, although a survival benefit has been reported for patients receiving ruxolitinib in comparison with those treated with placebo, best therapy, and historical controls, a Cochrane Review concluded that the evidence was insufficient to allow any conclusion regarding the efficacy of the drug in MF, with this being mainly due to the lack of statistical potency of the phase 3 trials to measure a possible survival gain. 9 A similar conclusion was reached by other authors. 10 they did not include comparators.…”

Section: Introductionsupporting

confidence: 83%

Does ruxolitinib prolong the survival of patients with myelofibrosis?

Cervantes

Pereira

2017

Blood

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Case presentation A 73-year-old man was diagnosed with primary myelofibrosis (PMF) after the incidental discovery of abnormalities in a blood test performed for the control of diabetes mellitus. The patient was asymptomatic. The spleen was palpable at 6 cm below the left costal margin. Hemoglobin was 10.9 g/dL; white blood cell count was 13.2 3 10 9 /L, with a leukoerythroblastic blood picture and 2% blasts, platelet count of 387 3 10 9 /L, and serum lactic dehydrogenase level of 1087 U/L. BCR/ABL was negative, and the JAK2 V617F mutation was found. Bone marrow cytogenetic study disclosed a normal 46,XY karyotype, and the marrow biopsy was typical of myelofibrosis. According to the International Prognostic Scoring System (IPSS), 1 the patient had intermediate-2 risk PMF, because of age over 65 years and blood blasts $1%. Median survival of patients with intermediate-2 risk PMF is 4 years. Because the patient was asymptomatic and not eligible for allogeneic stem cell transplantation, should he receive ruxolitinib to try to prolong his survival? Methods We searched the Medline database for references on ruxolitinib treatment. We considered only full published articles analyzing the effect of the drug on survival and including a comparator, either historical controls, placebo, or BAT. Because of this, studies on patients with intermediate-1 risk MF were not considered, as

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Section: Introductionsupporting

confidence: 83%

Does ruxolitinib prolong the survival of patients with myelofibrosis?

Cervantes

Pereira

2017

Blood

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“…disorders, in which adverse events, particularly those that are hematologically related, are understandably more frequent (11)(12)(13), and are consistent with findings from use of tofacitinib in the treatment of patients with psoriasis (14)(15)(16)(17)(18)(19). The occurrence of hair shedding in responders following drug cessation suggests that maintenance therapy may be required to sustain remissions.…”

Section: L I N I C a L M E D I C I N Esupporting

confidence: 76%

Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata

Mackay‐Wiggan¹,

Jabbari²,

Nguyen³

et al. 2016

JCI Insight

224

202

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IntroductionAlopecia areata (AA) is a major medical problem and is among the most prevalent autoimmune disease in the US, with a lifetime risk of 1.7% (1). AA affects both sexes across all ethnicities and represents the second most common form of human hair loss, second only to androgenetic alopecia (2). AA usually presents with patchy hair loss. One-third of these patients will experience spontaneous remissions within the first year. However, many patients' disease will progress to alopecia totalis (AT, total scalp hair loss) or alopecia universalis (AU, loss of all body hair). Persistent moderate-to-severe AA causes significant disfigurement and psychological distress in affected individuals (3). In clinical practice, there are no evidence-based treatments for AA (4), yet various treatments are offered, most commonly topical and intralesional steroids, which have limited efficacy.Our recent mechanistic studies demonstrated a dominant role for type I cellular immunity in AA pathogenesis, mediated by IFN-γ-producing NKG2D-bearing CD8 + cytotoxic T lymphocytes (CTLs) (5). The central role of type I cellular immunity is also reflected in the transcriptional landscape of AA lesional skin in humans and mice, which is dominated by IFN response genes and a CTL signature. These findings provided BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA.

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“…Z tego względu eksperci zalecają stosowanie ruksolitynibu z intencją zmniejszenia śledziony i objawów ogólnych choroby. Natomiast podkreślają, że nie ma wystarczających danych, aby lek włączano jako wykazujący wpływ na przedłużenie OS [31][32][33][34].…”

Section: Badania III Fazyunclassified

Miejsce ruksolitynibu w leczeniu chorych na mielofibrozę

Gołoś

Góra‐Tybor

2018

Hematologia

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Ruksolitynib, inhibitor kinazy JAK1/JAK2, jest pierwszym i dotychczas jedynym zarejestrowanym lekiem w leczeniu chorych na mielofibrozę (MF). Zmniejsza on wymiary śledziony oraz objawy ogólne choroby, takie jak świąd skóry, poty nocne czy utrata masy ciała. Głównymi działaniami niepożądanymi leku są małopłytkowość i niedokrwistość, a niehematologicznymi-immunosupresja i częstsze występowanie infekcji, w tym oportunistycznych. Ruksolitynib jako lek zmniejszający śledzionę i objawy ogólne choroby można stosować jako pomost przed procedurą przeszczepienia allogenicznych krwiotwórczych komórek macierzystych. W Polsce ruksolitynib jest dostępny w ramach programu lekowego dla chorych na MF z grup ryzyka pośredniego-2 i wysokiego z objawową splenomegalią i objawami ogólnymi.

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Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis

Cited by 36 publications

References 152 publications

Does ruxolitinib prolong the survival of patients with myelofibrosis?

Does ruxolitinib prolong the survival of patients with myelofibrosis?

Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata

Miejsce ruksolitynibu w leczeniu chorych na mielofibrozę

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