The Experts below are selected from a list of 27885 Experts worldwide ranked by ideXlab platform
Abraham Zlotogorski - One of the best experts on this subject based on the ideXlab platform.
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Janus Kinase inhibitors in dermatology a systematic review
Journal of The American Academy of Dermatology, 2017Co-Authors: Rony Shreberkhassidim, Yuval Ramot, Abraham ZlotogorskiAbstract:Background Janus Kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods This is a systematic review of PubMed and ClinicalTrials.gov. Results One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations It was not possible to perform a meta-analysis of the results. Conclusions This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
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Janus Kinase inhibitors in dermatology a systematic review
Journal of The American Academy of Dermatology, 2017Co-Authors: Rony Shreberkhassidim, Yuval Ramot, Abraham ZlotogorskiAbstract:Background Janus Kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods This is a systematic review of PubMed and ClinicalTrials.gov. Results One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations It was not possible to perform a meta-analysis of the results. Conclusions This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
Srdan Verstovsek - One of the best experts on this subject based on the ideXlab platform.
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Investigational Janus Kinase inhibitors in development for myelofibrosis.
Expert Opinion on Investigational Drugs, 2017Co-Authors: Prithviraj Bose, Abdallah Abou Zahr, Srdan VerstovsekAbstract:ABSTRACTIntroduction: Since the discovery of the activating V617F mutation in Janus Kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with many others having been discontinued for toxicity, and considerable uncertainty surrounding the future of those still in development.Areas covered: The available clinical data on pacritinib and momelotinib, the two agents in the most advanced phases of clinical testing in myelofibrosis, are examined in detail. NS-018 and INCB039110, selective inhibitors of JAK2 and JAK1, respectively, are also discussed. Finally, the JAK2 inhibitors no longer in clinical development are summarized in tabular form.Expert opinion: The different agents evaluated clearly differ in their kinomes, toxicity profiles and potential for myelosuppression. If approved, the JAK2-specific non-myelosuppressive inhibi...
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Comprehensive Kinase profile of pacritinib, a nonmyelosuppressive Janus Kinase 2 inhibitor
Journal of experimental pharmacology, 2016Co-Authors: Jack W. Singer, Suliman Al-fayoumi, Rami S. Komrokji, Ruben A. Mesa, Srdan VerstovsekAbstract:Pacritinib, potent inhibitor of Janus Kinase 2 (JAK2), JAK2V617F, and fms-like receptor tyrosine Kinase 3, is in Phase III development in myelofibrosis. Among type 1 inhibitors, pacritinib shows a lack of myelosuppression at doses that both inhibit JAK2/signal transducer and activator of transcription 3 pathway and demonstrate clinical efficacy. To elucidate these mechanisms and identify other disease targets, a kinome analysis screened 439 recombinant Kinases at 100 nM pacritinib concentration. For Kinases with >50% inhibition, pacritinib was titrated from 1 to 100 nM. JAK2, JAK2V617F, FLT3, colony-stimulating factor 1 receptor, and interleukin-1 receptor-associated Kinase 1 achieved half-maximal inhibitory concentrations
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Investigational Janus Kinase inhibitors.
Expert Opinion on Investigational Drugs, 2013Co-Authors: Srdan VerstovsekAbstract:Introduction: Dysregulation of the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway is central to the pathophysiology of myeloproliferative neoplasms (MPN). Small molecule inhibitors of JAK family members are currently under investigation for the treatment of MPN. Of these, ruxolitinib has received approval for clinical use in myelofibrosis in the United States and Europe. Areas covered: The clinical results and future development program of major JAK inhibitors, including ruxolitinib, CYT387, SAR302503, lestaurtinib, pacritinib, XL-019, LY2784544, BMS-911453, AZD1480 and NS-018 are reviewed. Expert opinion: JAK inhibitors are effective in relieving organomegaly (splenomegaly and hepatomegaly) and constitutional symptoms of myelofibrosis and some modulate inflammatory cytokines. However, they have little impact on disease burden and bone marrow fibrosis. The relationship between clinical efficacy, toxicity profile and specificity of JAK family member inhibition (i.e., JAK2 ...
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ruxolitinib an oral Janus Kinase 1 and Janus Kinase 2 inhibitor in the management of myelofibrosis
Postgraduate Medicine, 2013Co-Authors: Srdan VerstovsekAbstract:AbstractMyelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are referred to as the classic Philadelphia chromosome (BCR–ABL1)-negative myeloproliferative neoplasms. Although each has distinct pathologic features, all 3 display alterations in Janus Kinase (JAK) signal transduction activator of transcription signaling. Myelofibrosis is the most serious of the 3, associated with shortened survival (median survival, 5–7 years); bone marrow failure with anemia; progressive splenomegaly; and chronic, burdensome symptoms, including fatigue, night sweats, itching, abdominal discomfort, loss of appetite/early satiety, unintentional weight loss, and bone, chest, and abdominal pain. Treatments for MF have been mainly palliative, with the exception of allogeneic stem cell transplantation, which, although potentially curative, is feasible only in a small subpopulation of patients. In November 2011, ruxolitinib, an inhibitor of JAK1 and JAK2, was approved by the US Food and Drug Administratio...
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Janus Kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond
Nature Reviews Drug Discovery, 2011Co-Authors: Alfonso Quintás-cardama, Hagop M. Kantarjian, Jorge E. Cortes, Srdan VerstovsekAbstract:Activating mutations in Janus Kinase 2 (JAK2) are a common feature of a number of myeloproliferative neoplasms. JAKs are also involved in the pathogenesis of inflammatory and immune-mediated disorders, and several JAK inhibitors are now in clinical development. In this Review, Quintas-Cardama and colleagues discuss the current progress in this field.
Kim Papp - One of the best experts on this subject based on the ideXlab platform.
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treatment of plaque psoriasis with an ointment formulation of the Janus Kinase inhibitor tofacitinib a phase 2b randomized clinical trial
BMC Dermatology, 2016Co-Authors: Kim Papp, Melinda Gooderham, Jennifer Soung, Carla Mamolo, Vivek S Purohit, Robert Bissonnette, Lars Iversen, Steven R. Feldman, Zoe Diana Draelos, Cunshan WangAbstract:Background Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus Kinase inhibitor investigated for the topical treatment of psoriasis.
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a randomized phase 2a efficacy and safety trial of the topical Janus Kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis
British Journal of Dermatology, 2013Co-Authors: William C Ports, Manika Lamba, Robert Bissonnette, Chantal Bolduc, S. Khan, Kim PappAbstract:Background Tofacitinib (CP-690,550) is a novel Janus Kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis.
Rony Shreberkhassidim - One of the best experts on this subject based on the ideXlab platform.
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Janus Kinase inhibitors in dermatology a systematic review
Journal of The American Academy of Dermatology, 2017Co-Authors: Rony Shreberkhassidim, Yuval Ramot, Abraham ZlotogorskiAbstract:Background Janus Kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods This is a systematic review of PubMed and ClinicalTrials.gov. Results One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations It was not possible to perform a meta-analysis of the results. Conclusions This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
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Janus Kinase inhibitors in dermatology a systematic review
Journal of The American Academy of Dermatology, 2017Co-Authors: Rony Shreberkhassidim, Yuval Ramot, Abraham ZlotogorskiAbstract:Background Janus Kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods This is a systematic review of PubMed and ClinicalTrials.gov. Results One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations It was not possible to perform a meta-analysis of the results. Conclusions This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
Ivan Sola - One of the best experts on this subject based on the ideXlab platform.
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Janus Kinase 1 and Janus Kinase 2 inhibitors for treating myelofibrosis
Cochrane Database of Systematic Reviews, 2015Co-Authors: Arturo J Marticarvajal, Vidhu Anand, Ivan SolaAbstract:Background Myelofibrosis is a bone marrow disorder characterized by excessive production of reticulin and collagen fiber deposition caused by hematological and non-hematological disorders. The prognosis of myelofibrosis is poor and treatment is mainly palliative. Janus Kinase inhibitors are a novel strategy to treat people with myelofibrosis. Objectives To determine the clinical benefits and harms of Janus Kinase-1 and Janus Kinase-2 inhibitors for treating myelofibrosis secondary to hematological or non-hematological conditions. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2014, Issue 11), Ovid MEDLINE (from 1946 to 13 November 2014), EMBASE (from 1980 to 12 January 2013), and LILACS (from 1982 to 20 November 2014). We searched WHO International Clinical Trials Registry Platform and The metaRegister of Controlled Trials. We also searched for conference proceedings of the American Society of Hematology (from 2009 to October 2013), European Hematology Association (from 2009 to October 2013), American Society of Clinical Oncology (from 2009 to October 2013), and European Society of Medical Oncology (from 2009 to October 2013). We included searches in FDA, European Medicines Agency, and Epistemonikos. We handsearched the references of all identified included trials, and relevant review articles. We did not apply any language restrictions. Two review authors independently screened search results. Selection criteria We included randomized clinical trials comparing Janus Kinase-1 and Janus Kinase-2 inhibitors with placebo or other treatments. Both previously treated and treatment naive patients were included. Data collection and analysis We used the hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival, progression-free survival and leukemia-free survival, risk ratio (RR) and 95% CI for reduction in spleen size and adverse events binary data, and standardized mean differences (SMD) and 95% CI for continuous data (health-related quality of life). Two review authors independently extracted data and assessed the risk of bias of included trials. Primary outcomes were overall survival, progression-free survival and adverse events. Main results We included two trials involving 528 participants, comparing ruxolitinib with placebo or best available therapy (BAT). As the two included trials had different comparators we did not pool the data. The confidence in the results estimates of these trials was low due to the bias in their design, and their limited sample sizes that resulted in imprecise results. There is low quality evidence for the effect of ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR 0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR 0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the effect of ruxolitinib on progression free survival compared with BAT (HR 0.81, 95% CI 0.47 to 1.39). There is low quality evidence for the effect of ruxolitinib in terms of quality of life. Compared with placebo, the drug achieved a greater proportion of patients with a significant reduction of symptom scores (RR 8.82, 95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An additional trial showed significant differences in EORTC QLQ-C30 scores when compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to 14.85). The effect of ruxolitinib on reduction in the spleen size of participants compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08 to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low quality evidence). There is low quality evidence for the effect of the drug compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR 3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96). Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR 1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20; 95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3 or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT. The rate of neutropenia comparing ruxolitinib with standard medical treatment was not reported by the trial. Authors' conclusions Currently, there is insufficient evidence to allow any conclusions regarding the efficacy and safety of ruxolitinib for treating myelofibrosis. The findings of this Cochrane review should be interpreted with caution as they are based on trials sponsored by industry, and include a small number of patients. Unless powered randomized clinical trials provide strong evidence of a treatment effect, and the trade-off between potential benefits and harms is established, clinicians should be cautious when administering ruxolitinib for treating patients with myelofibrosis.
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The Cochrane Library - Janus Kinase‐1 and Janus Kinase‐2 inhibitors for treating myelofibrosis
Cochrane Database of Systematic Reviews, 2015Co-Authors: Arturo J Martí‐carvajal, Vidhu Anand, Ivan SolaAbstract:Background Myelofibrosis is a bone marrow disorder characterized by excessive production of reticulin and collagen fiber deposition caused by hematological and non-hematological disorders. The prognosis of myelofibrosis is poor and treatment is mainly palliative. Janus Kinase inhibitors are a novel strategy to treat people with myelofibrosis. Objectives To determine the clinical benefits and harms of Janus Kinase-1 and Janus Kinase-2 inhibitors for treating myelofibrosis secondary to hematological or non-hematological conditions. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2014, Issue 11), Ovid MEDLINE (from 1946 to 13 November 2014), EMBASE (from 1980 to 12 January 2013), and LILACS (from 1982 to 20 November 2014). We searched WHO International Clinical Trials Registry Platform and The metaRegister of Controlled Trials. We also searched for conference proceedings of the American Society of Hematology (from 2009 to October 2013), European Hematology Association (from 2009 to October 2013), American Society of Clinical Oncology (from 2009 to October 2013), and European Society of Medical Oncology (from 2009 to October 2013). We included searches in FDA, European Medicines Agency, and Epistemonikos. We handsearched the references of all identified included trials, and relevant review articles. We did not apply any language restrictions. Two review authors independently screened search results. Selection criteria We included randomized clinical trials comparing Janus Kinase-1 and Janus Kinase-2 inhibitors with placebo or other treatments. Both previously treated and treatment naive patients were included. Data collection and analysis We used the hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival, progression-free survival and leukemia-free survival, risk ratio (RR) and 95% CI for reduction in spleen size and adverse events binary data, and standardized mean differences (SMD) and 95% CI for continuous data (health-related quality of life). Two review authors independently extracted data and assessed the risk of bias of included trials. Primary outcomes were overall survival, progression-free survival and adverse events. Main results We included two trials involving 528 participants, comparing ruxolitinib with placebo or best available therapy (BAT). As the two included trials had different comparators we did not pool the data. The confidence in the results estimates of these trials was low due to the bias in their design, and their limited sample sizes that resulted in imprecise results. There is low quality evidence for the effect of ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR 0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR 0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the effect of ruxolitinib on progression free survival compared with BAT (HR 0.81, 95% CI 0.47 to 1.39). There is low quality evidence for the effect of ruxolitinib in terms of quality of life. Compared with placebo, the drug achieved a greater proportion of patients with a significant reduction of symptom scores (RR 8.82, 95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An additional trial showed significant differences in EORTC QLQ-C30 scores when compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to 14.85). The effect of ruxolitinib on reduction in the spleen size of participants compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08 to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low quality evidence). There is low quality evidence for the effect of the drug compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR 3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96). Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR 1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20; 95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3 or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT. The rate of neutropenia comparing ruxolitinib with standard medical treatment was not reported by the trial. Authors' conclusions Currently, there is insufficient evidence to allow any conclusions regarding the efficacy and safety of ruxolitinib for treating myelofibrosis. The findings of this Cochrane review should be interpreted with caution as they are based on trials sponsored by industry, and include a small number of patients. Unless powered randomized clinical trials provide strong evidence of a treatment effect, and the trade-off between potential benefits and harms is established, clinicians should be cautious when administering ruxolitinib for treating patients with myelofibrosis.
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The Cochrane Library - Janus Kinase-1 and Janus Kinase-2 inhibitors for treating myelofibrosis.
The Cochrane database of systematic reviews, 2015Co-Authors: Arturo J Martí-carvajal, Vidhu Anand, Ivan SolaAbstract:Background Myelofibrosis is a bone marrow disorder characterized by excessive production of reticulin and collagen fiber deposition caused by hematological and non-hematological disorders. The prognosis of myelofibrosis is poor and treatment is mainly palliative. Janus Kinase inhibitors are a novel strategy to treat people with myelofibrosis. Objectives To determine the clinical benefits and harms of Janus Kinase-1 and Janus Kinase-2 inhibitors for treating myelofibrosis secondary to hematological or non-hematological conditions. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2014, Issue 11), Ovid MEDLINE (from 1946 to 13 November 2014), EMBASE (from 1980 to 12 January 2013), and LILACS (from 1982 to 20 November 2014). We searched WHO International Clinical Trials Registry Platform and The metaRegister of Controlled Trials. We also searched for conference proceedings of the American Society of Hematology (from 2009 to October 2013), European Hematology Association (from 2009 to October 2013), American Society of Clinical Oncology (from 2009 to October 2013), and European Society of Medical Oncology (from 2009 to October 2013). We included searches in FDA, European Medicines Agency, and Epistemonikos. We handsearched the references of all identified included trials, and relevant review articles. We did not apply any language restrictions. Two review authors independently screened search results. Selection criteria We included randomized clinical trials comparing Janus Kinase-1 and Janus Kinase-2 inhibitors with placebo or other treatments. Both previously treated and treatment naive patients were included. Data collection and analysis We used the hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival, progression-free survival and leukemia-free survival, risk ratio (RR) and 95% CI for reduction in spleen size and adverse events binary data, and standardized mean differences (SMD) and 95% CI for continuous data (health-related quality of life). Two review authors independently extracted data and assessed the risk of bias of included trials. Primary outcomes were overall survival, progression-free survival and adverse events. Main results We included two trials involving 528 participants, comparing ruxolitinib with placebo or best available therapy (BAT). As the two included trials had different comparators we did not pool the data. The confidence in the results estimates of these trials was low due to the bias in their design, and their limited sample sizes that resulted in imprecise results. There is low quality evidence for the effect of ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR 0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR 0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the effect of ruxolitinib on progression free survival compared with BAT (HR 0.81, 95% CI 0.47 to 1.39). There is low quality evidence for the effect of ruxolitinib in terms of quality of life. Compared with placebo, the drug achieved a greater proportion of patients with a significant reduction of symptom scores (RR 8.82, 95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An additional trial showed significant differences in EORTC QLQ-C30 scores when compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to 14.85). The effect of ruxolitinib on reduction in the spleen size of participants compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08 to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low quality evidence). There is low quality evidence for the effect of the drug compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR 3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96). Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR 1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20; 95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3 or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT. The rate of neutropenia comparing ruxolitinib with standard medical treatment was not reported by the trial. Authors' conclusions Currently, there is insufficient evidence to allow any conclusions regarding the efficacy and safety of ruxolitinib for treating myelofibrosis. The findings of this Cochrane review should be interpreted with caution as they are based on trials sponsored by industry, and include a small number of patients. Unless powered randomized clinical trials provide strong evidence of a treatment effect, and the trade-off between potential benefits and harms is established, clinicians should be cautious when administering ruxolitinib for treating patients with myelofibrosis.
