***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Ruxolitinib , a selective inhibitor of Janus kinase ( JAK ) 1 and 2 , has clinical ly significant activity in myelofibrosis . METHODS In this double-blind trial , we r and omly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib ( 155 patients ) or placebo ( 154 patients ) . The primary end point was the proportion of patients with a reduction in spleen volume of 35 % or more at 24 weeks , assessed by means of magnetic resonance imaging . Secondary end points included the durability of response , changes in symptom burden ( assessed by the total symptom score ) , and overall survival . RESULTS The primary end point was reached in 41.9 % of patients in the ruxolitinib group as compared with 0.7 % in the placebo group ( P<0.001 ) . A reduction in spleen volume was maintained in patients who received ruxolitinib ; 67.0 % of the patients with a response had the response for 48 weeks or more . There was an improvement of 50 % or more in the total symptom score at 24 weeks in 45.9 % of patients who received ruxolitinib as compared with 5.3 % of patients who received placebo ( P<0.001 ) . Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group ( hazard ratio , 0.50 ; 95 % confidence interval , 0.25 to 0.98 ; P=0.04 ) . The rate of discontinuation of the study drug because of adverse events was 11.0 % in the ruxolitinib group and 10.6 % in the placebo group . Among patients who received ruxolitinib , anemia and thrombocytopenia were the most common adverse events , but they rarely led to discontinuation of the drug ( in one patient for each event ) . Two patients had transformation to acute myeloid leukemia ; both were in the ruxolitinib group . CONCLUSIONS Ruxolitinib , as compared with placebo , provided significant clinical benefits in patients with myelofibrosis by reducing spleen size , ameliorating debilitating myelofibrosis-related symptoms , and improving overall survival . These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period . ( Funded by Incyte ; COMFORT-I Clinical Trials.gov number , NCT00952289 . ) The r and omized , double‐blind , double‐dummy , phase 3b RELIEF trial evaluated  polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide ( also termed hydroxyurea ) but reported PV‐related symptoms . Patients were r and omized 1:1 to ruxolitinib 10 mg BID ( n = 54 ) or hydroxycarbamide ( prer and omization dose/schedule ; n = 56 ) ; crossover to ruxolitinib was permitted after Week 16 . The primary endpoint , ≥50 % improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster ( TSS‐C ; sum of tiredness , itching , muscle aches , night sweats , and sweats while awake ) at Week 16 , was achieved by 43·4 % vs. 29·6 % of ruxolitinib‐ and hydroxycarbamide‐treated patients , respectively ( odds ratio , 1·82 ; 95 % confidence interval , 0·82–4·04 ; P = 0·139 ) . The primary endpoint was achieved by 34 % of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16 . In a post hoc analysis , the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores ( ratio ≤ 2 ) receiving ruxolitinib than hydroxycarbamide ( 47·4 % vs. 25·0 % ; P = 0·0346 ) . Ruxolitinib treatment after unblinding was associated with continued symptom score improvements . Adverse events were primarily grade s 1/2 with no unexpected safety signals . Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide , although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life . We sought to vali date a broadly applicable 18-item instrument ( Myeloproliferative Neoplasm Symptom Assessment Form [ MPN-SAF ] , coadministered with the Brief Fatigue Inventory ) to assess symptoms of myelofibrosis , essential thrombocythemia , and polycythemia vera among prospect i ve cohorts in the United States , Sweden , and Italy . A total of 402  MPN-SAF surveys  were administered ( English [ 25 % ] , Italian [ 46 % ] , and Swedish [ 28 % ] ) in 161 patients with essential thrombocythemia , 145 patients with polycythemia vera , and 96 patients with myelofibrosis . Responses among the 3 administered language s showed great consistency after controlling for MPN subtype . Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Question naire-C30 . Enrolling physicians ' blinded opinion of patient symptoms ( 6 symptoms assessed ) were highly correlated with corresponding patients ' responses . Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated ( r > 0.5 , P < .001 ) and highly reproducible ( intraclass correlation coefficient > 0.7 ) . The MPN-SAF is a comprehensive and reliable instrument that is available in multiple language s to evaluate symptoms associated with all types of MPNs in clinical trials globally PURPOSE Myeloproliferative neoplasm ( MPN ) symptoms are troublesome to patients , and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies . We aim ed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy . PATIENTS AND METHODS The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score ( MPN-SAF TSS ) was calculated as the mean score for 10 items from two previously vali date d scoring systems . Questions focus on fatigue , concentration , early satiety , inactivity , night sweats , itching , bone pain , abdominal discomfort , weight loss , and fevers . RESULTS MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 ( st and ard deviation [ SD ] , 16.3 ) . MPN-SAF TSS results significantly differed among MPN disease subtypes ( P<.001 ) , with a mean of 18.7 ( SD , 15.3 ) , 21.8 ( SD , 16.3 ) , and 25.3 ( SD , 17.2 ) for patients with essential thrombocythemia , polycythemia vera , and myelofibrosis , respectively . The MPN-SAF TSS strongly correlated with overall quality of life ( QOL ; r=0.59 ; P<.001 ) and European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) functional scales ( all P<.001 and absolute r≥0.50 except social functioning r=0.48 ) . No significant trends were present when comparing therapy subgroups . The MPN-SAF TSS had excellent internal consistency ( Cronbach 's α=.83 ) . Factor analysis identified a single underlying construct , indicating that the MPN-SAF TSS is an appropriate , unified scoring method . CONCLUSION The MPN-SAF TSS is a concise , valid , and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospect i ve MPN symptom study to date . This new prospect i ve scoring method may be used to assess MPN symptom burden in both clinical practice and trial setting BACKGROUND Myelofibrosis is a Philadelphia chromosome – negative myeloproliferative neoplasm associated with cytopenias , splenomegaly , poor quality of life , and shortened survival . About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene ( JAK2 V617F ) that contributes to the pathophysiology of the disease . INCB018424 is a potent and selective Janus kinase 1 ( JAK1 ) and JAK2 inhibitor . METHODS We conducted a phase 1−2 trial of INCB018424 in patients with JAK2 V617F−positive or JAK2 V617F−negative primary myelofibrosis , post – essential thrombocythemia myelofibrosis , or post – polycythemia vera myelofibrosis . RESULTS A total of 153 patients received INCB018424 for a median duration of more than 14.7 months . The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses , on the basis of reversible thrombocytopenia . A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 ( STAT3 ) , a marker of JAK signaling , was demonstrated in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation . We studied additional doses and established that a 15-mg twice-daily starting dose , followed by individualized dose titration , was the most effective and safest dosing regimen . At this dose , 17 of 33 patients ( 52 % ) had a rapid objective response ( ≥50 % reduction of splenomegaly ) lasting for 12 months or more , and this therapy was associated with grade 3 or grade 4 adverse events ( mainly myelosuppression ) in less than 10 % of patients . Patients with debilitating symptoms , including weight loss , fatigue , night sweats , and pruritus , had rapid improvement . Clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myelofibrosis . CONCLUSIONS INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed . ( Funded by Incyte ; Clinical Trials.gov number , NCT00509899 . BACKGROUND Ruxolitinib , a Janus kinase ( JAK ) 1 and 2 inhibitor , was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study . We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus st and ard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea . METHODS We r and omly assigned phlebotomy-dependent patients with splenomegaly , in a 1:1 ratio , to receive ruxolitinib ( 110 patients ) or st and ard therapy ( 112 patients ) . The primary end point was both hematocrit control through week 32 and at least a 35 % reduction in spleen volume at week 32 , as assessed by means of imaging . RESULTS The primary end point was achieved in 21 % of the patients in the ruxolitinib group versus 1 % of those in the st and ard-therapy group ( P<0.001 ) . Hematocrit control was achieved in 60 % of patients receiving ruxolitinib and 20 % of those receiving st and ard therapy ; 38 % and 1 % of patients in the two groups , respectively , had at least a 35 % reduction in spleen volume . A complete hematologic remission was achieved in 24 % of patients in the ruxolitinib group and 9 % of those in the st and ard-therapy group ( P=0.003 ) ; 49 % versus 5 % had at least a 50 % reduction in the total symptom score at week 32 . In the ruxolitinib group , grade 3 or 4 anemia occurred in 2 % of patients , and grade 3 or 4 thrombocytopenia occurred in 5 % ; the corresponding percentages in the st and ard-therapy group were 0 % and 4 % . Herpes zoster infection was reported in 6 % of patients in the ruxolitinib group and 0 % of those in the st and ard-therapy group ( grade 1 or 2 in all cases ) . Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving st and ard therapy . CONCLUSIONS In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea , ruxolitinib was superior to st and ard therapy in controlling the hematocrit , reducing the spleen volume , and improving symptoms associated with polycythemia vera . ( Funded by Incyte and others ; RESPONSE Clinical Trials.gov number , NCT01243944 . ) BACKGROUND Treatment options for myelofibrosis 
    Output:
    
Although the small number of trials and potential for treatment bias in the review , treatment with RUX was associated with improved QoL and PRO in PV patients intolerant or resistant to hydroxyurea