Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.

Proportion of patients achieving Hct control at Week 28 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8. Phlebotomy eligibility was defined by: * Confirmed Hct \> 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or * Confirmed Hct \> 48% The confirmation occurred 2 to 14 days subsequent to the initial observation.

Time frame: Week 28

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

The ECOG scale of performance status described the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. The ECOG performance was recorded as per ECOG performance status grades ranging from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).

Time frame: Baseline and Week 28

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.

Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over

Population: Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Hematocrit is the percentage of red blood cells (RBC) in the blood.

Time frame: Baseline (last assessment before cross over), Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 64, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206, 219 and 232 after cross-over

Population: Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Hematocrit is the volume percentage of red blood cells (RBC) in the blood.

Time frame: Baseline, Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.

Time frame: Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.

Time frame: Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.

Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over

Population: Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+\[(1 Q2/(Q2+Q4))x(Q5/10)\] Percent activity impairment due to problem (past 7 says): Q6/10

Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over

Population: Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+\[(1 Q2/(Q2+Q4))x(Q5/10)\] Percent activity impairment due to problem (past 7 says): Q6/10

Time frame: Baseline, Week 4, 8, 16, 28, 52 and 80

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Proportion of patients achieving a complete hematological remission at Week 104 as defined by Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and * WBC \< 10 x10\^9/L at Week 104, and * Platelets ≤ 400 x 10\^9/L at Week 104 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.

Time frame: From Week 8 to Week 104, 156, 208 and 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Proportion of patients achieving a complete hematological remission at Week 28 was defined by: * Hct control at Week 28 defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and * WBC \< 10 x109/L at Week 28, and * Platelets ≤ 400 x 109/L at Week 28

Time frame: Week 28

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Proportion of patients achieving a complete hematological remission at Week 52, was defined by: * Hct control at Week 52, as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and * White Blood Count (WBC) \< 10 x10\^9/L at Week 52, and * Platelets ≤ 400 x 10\^9/L at Week 52 * Endpoint for Week 80 was defined, similarly.

Time frame: Week 52 and 80

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Proportion of patients achieving a Hct control at Week 104 as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104 and with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.

Time frame: From Week 8 to Week 104, 156, 208 and 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Proportion of patients achieving a Hct control at Week 52 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, and no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 \- Endpoint for Week 80 was defined, similarly.

Time frame: Week 52 and 80

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by: * Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) score reduction of greater than or equal to 10 points from baseline to Week 28, and * Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and * WBC \< 10 x10\^9/L at Week 28, and * Platelets ≤ 400 x 10\^9/L at Week 28, and * No palpable spleen at Week 28, and * No hemorrhagic or thrombotic events, and * No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).

Time frame: Week 28

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Proportion of participants developing any arterial or venous thromboembolic event

Time frame: From randomization to Week 80 for BAT and Week 260 for Ruxolitinib

Population: Safety Set comprised of all randomized participants who received at least one dose of ruxolitinib or BAT.

Proportion of patients who achieved partial remission at Week 104, based on the ELN and IWG-MRT criteria, as defined by: * MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 104, and * Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post-randomization and prior to Week 8, and * WBC \< 10 x10\^9/L at Week 104, and * Platelets ≤ 400 x 10\^9/L at Week 104, and * No palpable spleen at Week 104, and * No hemorrhagic or thrombotic events, and * No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria) Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.

Time frame: From Week 8 to Week 104, 156, 208 and 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Proportion of patients who achieved partial remission at Week 52 based on the ELN and IWG-MRT criteria, as defined by: * MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 52 and * Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and * WBC \< 10 x109/L at Week 52 and * Platelets ≤ 400 x 109/L at Week 52 and * No palpable spleen at Week 52 and * No hemorrhagic or thrombotic events, and * No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria). * Endpoint for Week 80 was defined, similarly.

Time frame: Week 52 and 80

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Overall survival (OS) event is defined as death due to any cause. OS events were counted in the BAT arm, irrespective of whether participants crossed over to receive ruxolitinib when the event occurred.

Time frame: up to Week 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Phlebotomy eligibility was defined by Confirmed Hct \> 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or Confirmed Hct \> 48%. The confirmation occurred 2 to 14 days subsequent to the initial observation.

Time frame: Baseline to Week 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Transformation-free survival is defined as one of the following: 1. Myelofibrosis (MF) as evidenced by bone marrow biopsy, or 2. Acute leukemia as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks. 3. Death due to any cause during treatment period

Time frame: Week 260 (ruxolitinib arm) and Week 80 (BAT arm)

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.

Time frame: Week 4, 8, 16, 28, 40, 52 and 80

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Spleen length was assessed by manual palpation at every study visit.

Time frame: Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260

Population: Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.

Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over

Population: Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

On-treatment deaths were reported from the day of first dose of study medication to the End of study (End of Treatment +30 days) visit which was Week 260 or prior (+30 days for Rux + crossover) and Week 80 or prior (+30 days for BAT only). Post-treatment deaths were reported following completion study treatment (Week 80 for patients receiving BAT, or Week 260 for patients receiving ruxolitinib) or from the time of premature discontinuation. Patients were followed for survival every three months up to end of study.

Time frame: Up to Week 260

Population: Safety Set comprised of all randomized participants who received at least one dose of ruxolitinib or BAT.