www.youtube.com/watch?v=MYnJdtHl7Cw
會員：小林10142678 發表時間:2018/10/29 下午 03:44:03
上週在紐約舉辦的11th International Congress On Myeloproliferative Neoplasms，
頁面左邊的Documents有會議手冊和各個簡報檔，很多資料值得一讀。
www.eventsquid.com/event.cfm?id=3081
其中這篇有興趣的可以去讀一下
Session 4.2 Gisslinger
Long-term Treatment of MPNs and IFNs
https://s3-us-west-2.amazonaws.com/eventsquid/Eventsquid/squid3-eventuploads-filename-c35ccb03-c9a6-652f-1444035b44258411.pdf
其中一個案例，這治療的結果真是棒。
Case No 1:
• Male patient (B.A), age: 81 years
• Diagnose PV in 2010 (JAK2 pos)
• Initial therapy: phlebotomy only, no history of VTE/AT
• Start with IFN-alfa 2b (PEGINVERA) 2011 – ongoing
starting dose 300µg every 2 weeks – continuous dose reduction
currently 35µg 1x/month
• Complete hematologic response
• Complete moleculargenetic reresponse
– DESPITE A VERY LOW IFN DOSE!!!
579 Evidence for Superior Efficacy and Disease Modification after Three Years of Prospective Randomized Controlled Treatment of Polycythemia Vera Patients with Ropeginterferon Alfa-2b Vs. HU/BAT
ash.confex.com/ash/2018/webprogram/Paper118715.html
新一代長效型干擾素P1101 組對應HU/BAT 組治療PV病患前瞻性隨機對照治療3年後的療效和疾病改善的證明
Monday, December 3, 2018: 7:30 AM
發表日期：2018年 12月3日星期一 7:30AM
Grand Hall D (Manchester Grand Hyatt San Diego)
地點：聖地牙哥曼徹斯特酒店大禮堂D
Background: Interferon-alpha (IFN) is being used in myeloproliferative neoplasms (MPNs) since years and remains the only known treatment with disease-modifying potential. Ropeginterferon alfa-2b (Ropeg) is a novel mono-pegylated IFN, with reduced dosing frequency and improved tolerability. Here, we report 3 years clinical data from the phase III PROUD/CONTI-PV trials with an additional emphasis on the first comprehensive, prospective, randomized, controlled genomic profiling including not only JAK2V617F, but longitudinal targeted sequencing to identify non-JAK somatic mutations and chromosomal aberrations.
背景：干擾素-α（IFN）多年來一直被用於治療骨髓增生性腫瘤（MPNs），並且仍然是唯一已知具有疾病修復的治療方法。Ropeginterferon alfa-2b（Ropeg）是一種新型長效型干擾素，具有較低的用藥頻率以及良好的耐受性。來自臨床三期PROUD / CONTI-PV 試驗的數據，進一步第一次全面性強調，從前瞻性，隨機，對照基因組分析，不僅包括JAK2V617F，還包括用於鑑定非JAK體細胞突變的縱向目標定序和染色體異常。
Study design: 254 PV patients (WHO 2008 criteria, naïve to cytoreduction or HU pretreated but not resistant) were randomized to receive Ropeg or hydroxyurea (HU) in the PROUD-PV study and were rolled over to CONTI-PV study after 12 months, with the option to switch from HU to best-available-therapy (BAT). Efficacy assessment included complete hematological response (CHR, by ELN criteria), and CHR plus symptom improvement (PV-related symptoms and signs including clinically significant splenomegaly). Secondary endpoints included JAK2V617F molecular response (MR, modified ELN criteria). Next-generation-sequencing (NGS, TruSight Myeloid Panel, Illumina) and genome-wide analysis (SNP 6.0, Affymetrix) was applied comprehensively as exploratory genetic work-up.
研究設計：254名PV病患（WHO 2008標準，新參與細胞減滅治療或先前治療HU但不耐受的病患）隨機接受PROUD-PV研究中的新一代長效型干擾素P1101或HU，並在12個月後轉入CONTI-PV研究，可以選擇由 HU 切換到最佳治療方式（BAT）。
療效評估包括完整血液學反應（CHR，ELN標準）和完整血液學反應加上疾病症狀改善（PV相關症狀和症狀，包括臨床上顯著的脾腫大）。次要終點包括JAK2V617F分子反應（MR，修飾的ELN標準）。次世代定序（NGS，TruSight Myeloid Panel，Illumina）和全基因組分析（SNP 6.0，Affymetrix）也全面採用作為探索性遺傳學研究。
Results: 83 (Ropeg) and 70 (HU/BAT) patients completed the 36-month efficacy analysis time point, mean treatment duration for safety analysis was 3.8 years. Median doses in the third year remained constant: 425 µg Ropeg every 2 weeks and 1,000 mg HU per day. In the HU/BAT arm over 97% of patients remained treated with HU.
結果：
83名（Ropeg）和70名（HU / BAT）病患完成了36個月的療程，安全性分析的平均治療持續時間為3.8年。治療第三年的中位劑量仍維持不變：每2週 425 μg 的P1101和每天 1,000mg HU。在HU / BAT組中，超過97％的患者仍然接受HU治療。
After 36 months of treatment, maintenance of higher responder rates (full analysis set) was shown in the Ropeg arm compared to HU/BAT for CHR (70.5% vs. 51.4%; p=0.0122; RR [95% CI]: 1.38 [1.07-1.79]) and for CHR plus symptom improvement (52.6% vs. 37.8%; p=0.0437; RR [95% CI]: 1.42 [1.01-2.00]). In contrast to HU/BAT, response rates were steadily increasing in the Ropeg arm throughout 24 months of treatment and remained constant after 36 months. Regarding safety, comparable numbers of patients experienced adverse events (89.8% for Ropeg, 90.6% for HU) and treatment-related adverse events (74.8% for Ropeg, 78.7% for HU). The most common (>10%) treatment-related adverse events anemia, thrombocytopenia and leukopenia occurred more frequently under HU, whereas GGT increase was mainly observed under Ropeg. No new safety signals appeared in the third year of treatment.
治療36個月後，P1101 組與 HU / BAT組相比有著較高的完全血液學反應（70.5％ vs 51.4％; p = 0.0122; 95％相對風險信賴區間：1.38 [ 1.07-1.79]）和完整血液學反應加上症狀改善（52.6％ vs 37.8％; p = 0.0437; 95％相對風險信賴區間：1.42 [1.01-2.00]）。
相較於HU / BAT，P1101組的反應率在24個月的治療期間穩定增加，並持續維持到36個月。關於安全性，相當數量的病患出現不良反應（P1101組為89.8％，HU組為90.6％）和治療相關不良事件（P1101組為74.8％，HU為78.7％）。HU組最常見（> 10％）治療相關的不良反應是貧血、血小板和白血球減少頻率更高，而P1101組主要則是GGT丙麩氨酸轉移酶異常。治療第三年沒有新的安全性風險發生。
Regarding JAK2V617F, after 36 months 66.0% of patients in the Ropeg arm but only 27.0% in the HU/BAT arm had achieved MR (p<0.0001; RR [95% CI]: 2.31 [1.56-3.42]). Importantly, MR strongly correlated with CHR.
關於JAK2V617F突變，36個月後，P1101組的病患66.0％ 但HU / BAT組僅有27.0％達到MR（p <0.0001; 95％相對風險信賴區間：2.31 [1.56-3.42]）。重要的是，分子反應與完全血液學反應密切相關。
The most common non-JAK mutations involved TET2 (15% of all patients), followed by DNMT3A, ASXL1, CUX1, CEBPA and EZH2. Besides frequent JAK-related chr9 aberrations (88% of patients), other cytogenetic aberrations were detected in 49 patients (23%).
最常見的非JAK突變是TET2（佔所有病患的15％），其次是DNMT3A、ASXL1、CUX1、CEBPA和EZH2。除了常見的JAK相關chr9異常（88％的病患），49位病患（23％）檢測到其他細胞遺傳學異常。
Although both treatments showed effects on the genomic level there were marked differences: HU appeared as potent suppressor of JAK2V617F only during the initial phase, while lacking the ability to suppress additional clones with different mutations. In contrast Ropeg was able to reduce also non-JAK allele burden including TET2. On the cytogenetic level, acquisition of novel genomic lesions occurred selectively under HU.
儘管兩種治療均顯示出對基因組水平的影響，但存在顯著差異：HU僅在初期治療階段作為JAK2V617F的有效抑制劑，但缺乏具有其他不同突變的克隆抑制能力。相反的，P1101也能夠減少非JAK突變的等位基因負擔包含TET2突變。在細胞遺傳學水平上，在HU治療下新的基因組病變會不定地發生。
In line with these molecular findings, disease or treatment related secondary malignancies occurred only in the HU cohort, including 2 cases of acute myeloid leukemia, 1 melanoma and 2 basaliomas, whereas in the Ropeg cohort 3 malignancies (glioblastoma, seminoma, adrenal neoplasm) most likely unrelated to IFNa treatment were reported. For one case of AML detailed longitudinal analysis revealed loss of JAK2V617F followed by rapid acquisition of DNMT3A and U2AF1 mutations shortly prior onset of leukemia.
與這些分子結果一致，疾病或治療相關的繼發性惡性腫瘤僅發生在HU組，包括2例急性骨髓性白血病、1例黑色素瘤和2例基底細胞瘤，而在P1101組中3例惡性腫瘤（膠質母細胞瘤，精原細胞瘤，腎上腺腫瘤）, 報告顯示應與干擾素治療無關。對於其中一例急性骨髓性白血病病患，雖然顯示 JAK2V617F突變消失，但隨後在白血病發作前不久即迅速獲得DNMT3A和U2AF1突變。
Conclusions: These data demonstrate high and durable hematologic responses and symptom control with good tolerability under Ropeg. The effect not only on JAK2V617F but other mutations involved in MPNs and on cytogentic aberrations confirm the concept of disease modification capability of IFNa. Ropeginterferon alfa-2b will provide a valuable and safe new long-term treatment option with features distinct from other treatment modalities including HU.
結論：
這些數據證明了P1101下具有良好耐受性且穩定的血液學反應和症狀控制。不僅能夠JAK2V617F突變產生影響，且對於涉及MPN和細胞遺傳學異常的其他突變產生效果，這也證實了干擾素的疾病修復能力。P1101將提供不同於HU和其他治療方式上長期治療上有價值且安全的治療選擇。
事實發生日107/11/01
說明
1.事實發生日:107/11/01
2.公司名稱:藥華醫藥股份有限公司
3.與公司關係(請輸入本公司或子公司):本公司
4.相互持股比例:不適用
5.發生緣由:
本公司接獲中國國家藥品監督管理總局 (China Food and Drug Administration,CFDA)批准Ropeginterferon alpha 2b (P1101) 以進口生物藥在中國進行臨床試驗。
6.因應措施:無
7.其他應敘明事項:
(1)研發新藥代號或名稱：Ropeginterferon alfa-2b（P1101）
(2)用途:P1101係最新一代長效型干擾素藥物，可用於治療真性紅血球增生症(PV)、原發性血小板增生症(ET)、原發性骨髓纖維(PMF)及慢性病毒性肝炎(HBV/HCV)等。
(3)預計進行之所有研發階段：在完成笫一期健康人的藥物動力及藥效動力臨床試驗後，擬依規範申請免除二、三期臨床試驗並再做一個單臂（single arm）橋椄（bridging study）臨床實驗，以加速新藥上市流程。
(4)目前進行中之研發階段：
(一)提出申請/通過核准/不通過核准：
本公司自主創新研發新生物藥Ropeginterferon alfa-2b（P1101）向中國CFDA提出以進口生物藥申請人體臨床試驗，已接獲中國國家藥品監督管理局批准在中國進行臨床試驗。
(二)未通過目的事業主管機關許可者，公司所面臨之風險及因應措施：不適用
(三)已通過目的事業主管許可者，未來經營方向：不適用
(四)已投入之累積研發費用：因應未來市場行銷策略，以及保障公司及投資人權益，故不予公開揭露。
(5)將再進行之下一研發階段：
A.預計完成時間：預計2019年完成。
B.預計應負擔之義務：無。
(6)市場現況
真性紅血球增生症（PV）目前除了二線用藥Jakafi外，沒有其他核准的藥品，僅能靠定期放血來維持正常血液濃度，不僅不方便還可能因為重複放血引發其他併發症，如血小板過多症等等，嚴重影響病人生活品質。短效或傳統的PEG 干擾素藥物一直以來都被認為能夠治癒血液疾病，但是缺點為副作用過大難以被病人廣泛接受。 數十年來短效及傳統PEG長效干擾素已被廣泛使用治療MPNs病患，但其藥物副作用大、病人忍受度差而導致劑量難以調升以致療效無法提升。
本公司的P1101經近十年來的第一、第二及第三期人體臨床試驗所得臨床數據已證明P1101已可大幅降低副作用、提升安全性且劑量調整幅度大，已達極高之治癒率，特別在醫藥史上第一次證明可以安全採每二週給藥一次，相較每週給藥一次的傳統PEG干擾素 （pegylated interferons）來說，P1101除具高療效外，更提供了更好的耐受性和方便性。
在肝炎治療方面，據世界衛生組織估計，全世界B型肝炎患者約有4億人口，C型肝炎患者約為1億7000萬人。發展P1101為治療肝炎用藥的策略，會著重在公共衛生還需加強的國家； 如大陸及其他新興國家。全球肝炎用藥市場超過100億美金。 但因干擾素藥品不良副作用，其用於肝炎治療的市場在2011年僅約為30億美金。P1101為一長效且副作用輕微的干擾素藥物，定能增加干擾素藥物在治療肝炎的市場占有率。
(7)新藥開發時程長、投入經費高且並未保證能一定成功，此等可能使投資面臨風險，投資人應審慎判斷謹慎投資。
3030 Long-Term Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Polycythemia Vera – Final Phase I/II Peginvera Study Results
ash.confex.com/ash/2018/webprogram/Paper118584.html
藥華藥新一代干擾素Ropeginterferon Alfa-2b在PV病患中的長期療效和安全性 – 臨床I / II期Peginvera試驗最終研究結果
Sunday, December 2, 2018, 6:00 PM-8:00 PM
簡報時間：2018年12月2日, 週日 6:00-8:00 PM
Hall GH (San Diego Convention Center)
地點：聖地牙哥會議中心大廳
Background: Ropeginterferon alfa-2b (Ropeg) is a novel long-acting monopegylated IFN-alpha-2b. Due to reduced dosing frequencies, better tolerability and improved compliance, Ropeg may be a favorable treatment option for long-term therapy in patients with polycythemia vera (PV).
研究背景：
藥華藥新一代干擾素 Ropeginterferon alfa-2b（Ropeg）是一種新型長效型干擾素。由於給藥頻率降低，耐受性更佳，病患依從性更好，P1101可能是PV病患長期治療的較佳治療選擇。
Study design: PEGINVERA phase I/II (NCT: 2010-018768-18), a prospective, open-label, multicenter study, investigated the efficacy and safety of Ropeg for long-term treatment in 51 patients aged ≥18 years with a confirmed diagnosis of PV, regardless of prior cytoreductive therapy. Following ≥1 year of 2-weekly treatment, patients who responded well to Ropeg were permitted to switch to a 4-weekly dosing regimen.
研究設計：
PEGINVERA I / II期（NCT：2010-018768-18）是一項前瞻性、開放式、多中心研究，研究了P1101對51名年齡≥18歲的PV不論先前有無接受細胞減滅療法的PV病患進行長期治療的有效性和安全性研究。在為期超過一年的每2週治療方案後，將病患轉為每4週一次的治療方案後，病患轉換良好。
Results: Baseline characteristics of the study cohort and interim safety and efficacy data were presented previously (Gisslinger et al., Blood, 2015). Fifty-one patients were treated: Median exposure to Ropeg was approximately 5.1 years (61 months; range: 0 to 87 months). Patients were treated for a median of approximately 2 years (98.9 weeks; (Q1-Q3: 69.0 – 117.4 weeks) on the 2-weekly regimen and 4 years (207.1 weeks; Q1-Q3: 158.6 - 242.0 weeks) on the 4-weekly regimen.
結果：
先前提出了研究安全性和有效性數據（Gisslinger等，Blood，2015）。 51名病患接受治療：平均治療P1101的治療中位數約為5.1年（61個月；範圍：0-87個月）。病患在每2週一次的治療方案中治療中位數約為2年（98.9週;（Q1-Q3：69.0-117.4週），每4週一次的治療方案治療中位數為4年（207.1週; Q1-Q3：158.6-242.0週）。
The best observed individual hematological response for patients in the efficacy analysis set (FAS) was a complete hematological response for 27/42 (64.3%) and a partial response for 14/42 (33.3%) patients. Patients required a median of 34 weeks (Q1-Q3: 10-96 weeks) treatment to achieve a complete hematological response, and 10 weeks (Q1-Q3: 10-20 weeks) to achieve any hematological response. Switch from 2 to 4-week dosing regimen had no apparent effect on maintenance of response.
在療效分析上觀察到病患最佳的完全血液學反應為27/42（64.3％）而部分血液學反應為14/42（33.3％）。病患需要治療中位數34週（Q1-Q3：10-96週）以達到完全血液學反應，並且需要治療中位數10週（Q1-Q3：10-20週）以達到任何血液學反應。從每2周一次的治療方案切換到4週一次的治療方案並無明顯影響到反應率。
With respect to JAK-2 allele burden, the best observed individual molecular response was a complete response for 12/42 (28.6%) patients and a partial response for 19/42 (45.2%) patients. Lowest JAK-2 values relative to baseline are presented by patient in Figure 1. Patients required a median of 82 weeks (Q1-Q3: 44-115 weeks) treatment to achieve a complete molecular response and 34 weeks (Q1-Q3: 18-55 weeks) treatment to achieve any molecular response. Irrespective of dosing regimen, molecular responses tended to increase over time.
關於JAK-2等位基因負荷部分，觀察到病患最佳的完全分子反應為12/42（28.6％）和19/42（45.2％）病患的部分分子反應。圖1呈現出相對於基準的最低JAK-2數值。病患需要治療中位數82週（Q1-Q3：44-115週）以得到完全的分子反應和34週（Q1-Q3：18- 55週）治療達到任何分子反應。無論何種治療方式，分子反應都會隨著治療時間的推移而增加。
Most patients reported at least one adverse reaction (AR) to treatment (409 ARs in 48/51 [94.1%]); however, the majority (296 in 44 [86.3%] patients) were mild; 102 (in 34 [66.7%] patients) were moderate and 11 (in 10 [19.6%] patients) were severe. The most frequently reported ARs (frequency >20%) were arthralgia, influenza-like illness and fatigue. Twelve serious treatment emergent adverse events (TEAE) reported by 8/51 patients (15.7%) were considered to be treatment related: 2 events of depression, 2 of positive anti-thyroid antibodies, and one each of acute stress disorder, increased antinuclear antibodies, arthralgia, atrial fibrillation, fatigue, influenza-like illness, pyrexia, and increased transaminases.
大多數病患在治療期間至少有一種不良反應（AR）（48/51病患中有409種不良反應 [94.1％]）；大多數是輕微的（44名病患中提報296種[86.3％]）; 102種不良反應為中度（34名病患[66.7％]），11種不良反應為嚴重（10名病患[19.6％]）。
最常提到的不良反應（頻率> 20％）是關節痛，類似流感的疾病和疲勞。8/51名病患（15.7％）呈現出的12種治療期間出現的不良反應（TEAE）被認為與治療相關、2名病患抑鬱症、2名出現抗甲狀腺抗體陽性，1名出現急性壓力障礙
，抗核抗體增加、關節痛、心房顫動、疲勞、類流感疾病、發熱和ALT升高。
25 patients completed the trial. The majority of discontinuation due to TEAE (13/21 patients) occurred in the first year, when the recommended slow up-titration of Ropeg could not be applied because of the maximum-tolerated-dose design. After the first year, only 8 additional patients discontinued because of TEAE.
25名病患完成了試驗。由於治療期間出現的不良反應（13/21病患）病患中大部分停藥發生在第一年，這是因為最大耐受劑量設計導致P1101劑量上調後無法適應。在第一年治療後，由於治療期間出現的不良反應而中斷治療的僅有8名病患。
Conclusions:
The final results of this phase I/II study of Ropeg in patients with PV support the findings of the pivotal phase III clinical trial (Gisslinger et al., Blood 2015) with respect to safety and efficacy as determined by hematological, clinical and molecular parameters. In addition, these data provide evidence that treatment with Ropeginterferon alfa-2b for up to 7 years is efficacious, well-tolerated and disease-modifying at both the 2 week and 4 week maintenance treatment regimens.
結論：
藥華藥新一代長效型干擾素P1101對於PV病患的臨床I / II期研究的最終結果包含血液學反應、臨床和分子反應中安全性和有效性的結果支持臨床三期試驗（Gisslinger等，Blood 2015）。
此外，這些數據顯示，使用P1101在長期7年的治療期間不論是每2周/每4周一針的治療方案中都證實是有效的、耐受性佳以及可以修復疾病的。
3029 Effect of Ropeginterferon Alfa-2b in Prefibrotic Primary Myelofibrosis
新一代長效型干擾素Ropeginterferon Alfa-2b在原發性骨髓纖維化中(PMF)的作用
https://ash.confex.com/ash/2018/webprogram/Paper119268.html
Sunday, December 2, 2018, 6:00 PM-8:00 PM
簡報日期：2018年12月2日周日 6:00-8:00
Hall GH (San Diego Convention Center)
地點：聖地牙哥會議中心大廳
Primary myelofibrosis (PMF) is a clonal stem cell disorder currently classified as myeloproliferative neoplasm (MPN). Median survival in PMF is estimated with 6 years, but can range from few months to several decades in early pre-fibrotic PMF. The disease course is almost always complicated by progressive anemia, symptomatic splenomegaly and severe constitutional symptoms.
Causes of death include leukemic transformation with marrow failure and complications from bleeding, thrombosis, portal hypertension or infections. While PMF patients in advanced stages benefit from a JAK2 inhibitor therapy, there is no evidence for prevention of disease progression to overt MF by an early therapeutic intervention. Interferon alpha has been shown to reduce white cell counts, elevated platelet counts and improve splenomegaly and there are some observations of its disease modifying capability in the earlier phase of PMF.
原發性骨髓纖維化（PMF）是一種克隆性幹細胞疾病，目前被列為骨髓增生性腫瘤（MPN）。PMF的中位生存期估計為6年，但PMF在纖維化早期生存範圍在幾個月到幾十年之間。疾病總是伴隨著漸進性貧血、脾腫大和嚴重的全身性症狀。死亡原因包括骨髓衰竭的白血病轉化且伴隨出血、血栓、門靜脈高壓或感染的併發症。雖然後期的PMF病患受益於JAK2抑制劑的治療，但沒有證據顯示早期治療可預防疾病惡化為骨髓纖維化(MF)。干擾素α已被證明可以減少白血球數量計數、提升血小板數量以及改善脾臟腫大，並且在PMF的早期階段即觀察到疾病修復能力。
The aim of the present phase II study was to test the capability of a novel pegylated interferon compound (Ropeginterferon-alfa-2b) to improve hematologic parameters, splenomegaly and to monitor the course of the disease concerning clinical symptoms in a homogeneous cohort of early pre-fibrotic PMF patients. The endpoints of the study were hematological response, maintenance or improvement of quality of life and the symptom scales during a period of 2 years interferon treatment, and interferon tolerability.
本次臨床二期研究的目的是測試新一代長效型干擾素P1101（Ropeginterferon-alfa-2b）改善血液學參數、脾腫大和監控早期纖維化的PMF病患臨床症狀的疾病的能力。該研究的終點是在兩年期的干擾素治療期間血液學反應、生活品質的維持或改善以及治療期間的症狀量表以及干擾素耐受程度。
Twenty-five patients were included in the study. Nine patients were pretreated with pegylated interferon alfa 2b (PegIntron or Pegasys) during at least 3 years and 16 patients were interferon naïve. At start of therapy the median red blood cell count was 4.3 T/l (3.3–5.2); median hemoglobin level was 12.5 g/dl (9.6 – 14.7 g/dl), median WBC count was 7.7 G/l (2.44–27.55 G/l) and the median platelet count was 435 G/l (124 – 1161 G/l). Median LDH-level was 263.5 U/l (163–538 U/l) and the median spleen size was 11.2 cm (8–22 cm). 13 patients were JAK2 positive, and 12 patients were CALR positive. Detailed patient characteristics in 6-month intervals for pretreated and interferon naïve patients are given in Table 1.
該研究納入了25名病患。 9名病患在先前至少使用長效型干擾素(PegIntron or Pegasys)治療3年期間，16名為新使用干擾素進行治療的病患。
治療開始時病患紅血球數中位數為4.3 T/l（3.3-5.2）；血紅蛋白中位數水平為12.5 g/dl（9.6-14.7 g/dl），白血球中位數為7.7 G/l（2.44-27.55 G/l），血小板數量中位數為435 G/l（124 - 1161 G/l））。乳酸脫氫酵素中位數為263.5 U/l（163-538 U/l），脾臟大小中位數為11.2 cm（8-22 cm）。13名病患檢測為JAK2陽性，12名病患為CALR陽性。
表1給出了預先使用干擾素以及初期使用干擾素治療病患6個月間隔的詳細病患特徵。
At study entry, 12 patients presented with anemia, 12 with thrombocytosis, 9 with leukocytosis, 14 with elevated LDH levels and 7 with splenomegaly. After 24 months of treatment, 6 patients improved their anemia (N=2 pretreated, 4 treatment-naïve), 6 their thrombocytosis (N=6 treatment-naïve), 7 their leukocytosis (N=7 treatment-naïve), 6 normalized LDH levels (N=1 pretreated, 5 treatment-naïve) but none showed response in the form of significant spleen size reduction. The fact that no patient showed disease progression in any single parameter after 2 years of treatment can already be considered a success.
在研究開始時，12名病患出現貧血、12名病患有血小板增多症、9名患有白血球增多症，14名病患的乳酸脫氫酵素(LDH)水平增加，7名患有脾臟腫大。
治療24個月後，6名病患改善貧血（2名預先使用干擾素治療，4名初期使用干擾素治療），6名改善血小板增多症（6名均為初期使用干擾素治療），7名改善白血球增多症（7名均為初期使用干擾素治療），6名病患乳酸脫氫酵素(LDH)恢復正常水平（1名預先使用干擾素治療，5名初期使用干擾素治療），但沒有人有顯著的脾臟大小減少的反應。在2年治療期間，沒有病患在任何單一參數中顯示疾病惡化的事實，這被認定為成功的治療方式。
The most common side effects observed during this study include flu-like symptoms (N=7 pretreated, 15 treatment-naïve), lack of concentration (N=3 pretreated, 8 treatment-naïve), pruritus (N=2 pretreated, 7 treatment-naïve), infections (N=2 pretreated, 5 treatment-naïve) and bleeding (N=2 pretreated, 4 treatment-naïve). Generally, pretreated patients suffered from fewer side effects than treatment-naïve patients in every category. This may be due to the fact that those patients had already been exposed to an interferon in previous treatment regimen. Two patients had to be withdrawn from the study after approximately 12 months due to psychological side effects, both from the treatment-naïve group.
在這項研究中觀察到最常見的副作用包括類流感症狀（7名預先使用干擾素治療，15名初期使用干擾素治療）、注意力不集中（3名預先使用干擾素治療，8名初期使用干擾素治療）、瘙癢（2名預先使用干擾素治療，7名初期使用干擾素治療）、感染（2名預先使用干擾素治療，5名初期使用干擾素治療）和出血（2名預先使用干擾素治療，4名初期使用干擾素治療）。
一般來說，預先使用干擾素治療的病患副作用比初期使用干擾素治療病患要少。這可能是由於這些病患在之前的治療方案中已經處在干擾素治療的狀況。由於心理面的副作用影響，兩名病患在大約12個月後退出研究，這兩位也都是初期使用干擾素治療病患。
Additionally to conventional symptom screening, the EORTC-QLQ-C30 questionnaire was used to assess therapy-response. With this tool, function scales, symptom scales and quality-of-life were recorded. After 24 months of treatment, almost every category showed improvement for both pretreated and treatment-naïve patients. Detailed results about symptom scales are shown in Figure 1.
除常規症狀篩檢外，EORTC-QLQ-C30問卷用於評估治療反應。使用此工具用來記錄功能量表，症狀量表和生活品質。治療24個月後，幾乎每個類別都顯示出預先使用干擾素治療以及初期使用干擾素治療的病患有所改善。關於症狀量表的詳細結果如圖1所示。
In conclusion, the data demonstrate that Ropeginterferon-alfa-2b is able not only to induce hematologic responses but also to improve constitutional symptoms and overall quality of life in prefibrotic PMF. Thus ropeginterferon-alfa-2b warrant further investigation as a treatment option in prefibrotic PMF, where only very limited alternatives exist.
總之，數據顯示出，藥華藥新一代長效型干擾素Ropeginterferon-alfa-2b不僅能誘導血液學反應，還能改善纖維化前期的PMF病患全身症狀以及整體生活品質。因此，在纖維化前期的PMF的有限治療選擇下，藥華藥新一代長效型干擾素Ropeginterferon-alfa-2b需要進一步研究以作為治療選項。
Q3 2018 Incyte Corporation Earnings Conference Call
https://investor.incyte.com/static-files/59d4d250-6796-4bc5-818f-9cd8c8bd89df
# Incyte 公布 Q3財報顯示出, 2018年JAKAFi 前三季累計營收已超越10億美金, 營收不論單季年增率或累計年增率均持續增長動能。
# 營收動能持續, 2018年前9月產品營收累計年增25%
(可參考藍色 Jakafi 營收成長柱狀圖, 橘色 Jakavi 銷售權利金)
# 使用 Jakafi 的人數持續增加, 累計至2018年Q3 為止統計使用JAKAFi 進行治療之病患已超過 12500名, 估計Jakafi 2018年營收達 13.7-14億美金
# Jakafi 於 於 2011年被FDA 取得MF 一線用藥核可; 2014年被FDA 取得PV 二線用藥核可;
使用JAKAFi 進行治療之MF 病人數年增率9% ;
使用JAKAFi 進行治療之PV 病人數年增率18%
(藍色 為 MF, 橘色為 PV)
# 下圖說明 JAK抑制劑適用於治療多種適應症
PV 於 2014年被FDA 取得二線用藥核可, 25000名目標病患中, 滲透率達 20%
MF 於 2011年被FDA 取得一線用藥核可, 16000名目標病患中, 滲透率達 40%
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