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武田发布评估HYQVIA®用于慢性炎性脱髓鞘性多发性神经根神经病(CIDP)维持治疗的枢纽性3期临床试验阳性顶线结果

2022-07-25 网络 网络

数据显示,HYQVIA®[免疫球蛋白输注液10%(人类)暨重组人类透明质酸酶]维持治疗组的慢性炎性脱髓鞘性多发性神经根神经病复发率低于安慰剂

武田(Takeda, TSE:4502/NYSE:TAK)今天宣布ADVANCE-1达到主要终点。ADVANCE-1是一项随机、安慰剂对照、双盲3期临床试验,评估HYQVIA®[免疫球蛋白输注液10%(人类)暨重组人类透明质酸酶]用于慢性炎性脱髓鞘性多发性神经根神经病(CIDP)的维持治疗。顶线数据显示,HYQVIA维持治疗可减少CIDP的神经肌肉残疾及损伤的复发,为其作为促进性皮下免疫球蛋白(fSCIG)解决方案的潜力提供了数据支持。该解决方案或可允许众多CIDP患者每月输注一次。ADVANCE-1的分析正在进行中,公司预计在即将召开的医学论坛上披露更多数据。 

枢纽性ADVANCE-1临床试验评估HYQVIA在132例成人CIDP患者中的有效性、安全性和耐受性。这些患者在输注前接受静脉内免疫球蛋白(IVIG)治疗稳定给药方案至少3个月。主要终点分析显示,按《炎性神经病病因和治疗量表》(INCAT),HYQVIA剂量和给药间隔与该患者既往IVIG相同时,其CIDP复发率低于安慰剂[分别为9.7%和31.4%;p值=0.0045]。本研究多数患者接受每4周HYQVIA给药一次方案。 

武田血浆衍生疗法事业部研发负责人Kristina Allikmets表示:“虽然静脉内注射免疫球蛋白治疗CIDP的有效性和安全性已得到公认,1但CIDP患者长期用药会带来沉重的负担。非常需要一种既有效又可以每月一次在家或医院给药的治疗,减少输液部位的数量,减少给药持续时间和频次。我们致力于尽快将这种疗法带给CIDP患者。” 

慢性炎性脱髓鞘性多发性神经根神经病是一种罕见的慢性自身免疫性疾病,可累及周围神经系统。2,3该病况可导致手臂和腿脚进行性对称性无力和感觉功能受损。2免疫球蛋白治疗因其广泛的、多方面、抗炎和免疫调节效应已成为CIDP患者的标准治疗。4,5,6

ADVANCE-1顶线分析结果显示,HYQVIA安全性良好,进一步支持其用作CIDP的维持治疗。在HYQVIA治疗的62例患者中,多数治疗相关不良事件报告为轻度或中度。未报告新的HYQVIA安全性风险。进行中的ADVANCE-3临床试验数据将进一步支持HYQVIA对CIDP的安全性,ADVANCE-3是同类研究中延伸期最长的研究,部分参研者的随访数据长达6年。7

在全部数据分析后,武田计划在2022财年向美国和欧盟的监管部门报批HYQVIA。 

 

关于慢性炎性脱髓鞘性多发性神经根神经病(CIDP)

慢性炎性脱髓鞘性多发性神经根神经病(CIDP)是一种累及周围神经系统的慢性、获得性、免疫介导疾病,其特征是肢体远端及近端进行性、对称性无力以及四肢感觉功能受损。CIDP是一种罕见、致残性、缓慢进展性或复发性疾病,8全球患病率约为每10万人中有0.67-10.3例。CIDP的主要症状进展缓慢,导致准确诊断可延迟数月至数年。2,10

关于HYQVIA®

HYQVIA® [免疫球蛋白输注液10%(人类)暨重组人类透明质酸酶]是一种含有重组人类透明质酸酶和免疫球蛋白(Ig)的液体药物,在美国获准用于治疗原发性免疫缺陷(PI)成人患者。同时在欧盟获准作为成人、儿童和青少年原发性免疫缺陷和继发性免疫缺陷(SID)的替代疗法。这些患者患有重度或复发性感染,抗菌治疗无效,被证实特异性抗体失效(PSAF)或血清IgG水平<4克/升。HYQVIA经皮下注入皮下脂肪组织。HYQVIA含有采自人类血浆的免疫球蛋白。免疫球蛋白是维持人体免疫系统的抗体。HYQVIA的透明质酸酶部分有助于人体吸收更多的免疫球蛋白。HYQVIA每月最多输注一次(每3或4周)。如需了解有关HYQVIA的更多信息,请访问HyQvia.com。 

美国版适应证与用药限制

HYQVIA适用于治疗成人原发性免疫缺陷。HYQVIA仅供皮下给药。HYQVIA中的重组人类透明质酸酶在原发性免疫缺陷之外各类病况中长期用药的安全性和有效性尚未确立。 

美国版重要安全性信息

警示:血栓形成

  • 包括HYQVIA在内的免疫球蛋白产品可导致血栓形成。风险因素可包括高龄、长时间不活动、高凝状态、静脉或动脉血栓形成史、使用雌激素、留置血管导管、高粘血症和心血管风险因素。血栓形成可发生于没有已知危险因素的情况下。
  • 对于有血栓形成风险的患者,应以可行的最低剂量和输注速度进行HYQVIA给药。给药前应确保患者水分充足。
  • 有高粘血症风险的患者应监测血栓形成的体征和症状,并评估血液粘度。

禁忌症

  • 对人类免疫球蛋白的过敏性或重度全身性超敏反应史
  • 伴IgA抗体的IgA缺陷患者和对人类免疫球蛋白的超敏反应史
  • 已知对透明质酸酶(包括HYQVIA的重组人类透明质酸酶)有全身性超敏反应
  • 已知对(透明质酸酶溶液中的)人类白蛋白有全身性超敏反应

警示与注意事项

  • 超敏反应:可发生重度超敏反应,即使对于既往耐受人类免疫球蛋白治疗的患者也不例外。若有发生超敏反应,应立即停止输注并给与相应治疗。伴IgA抗体的IgA缺陷患者发生潜在重度超敏反应(包括过敏反应)的风险较高。
  • 血栓形成:可发生于免疫球蛋白产品治疗后,且无已知风险因素。对于风险患者,应以可行的最低剂量和输注速度给药。给药前应确保水分充足。有高粘血症风险的患者应监测血栓形成的体征和症状,并评估血液粘度。
  • 重组人类透明质酸酶(rHuPH20)免疫原性:可产生针对重组人类透明质酸酶成分的非中和抗体。此类抗体的临床意义或其能否干扰人类受精尚属未知。
  • 无菌性脑膜炎综合征:免疫球蛋白用药中已有报道,女性可能较常见。有体征和症状表现的患者应进行全套神经系统检查,以排除脑膜炎的其他病因。停用免疫球蛋白治疗后可在数天内缓解,未见后遗症。
  • 溶血:HYQVIA含有可能导致阳性直接抗球蛋白反应和溶血的血型抗体。患者应监测有无溶血和迟发性溶血性贫血的体征和症状,若有存在,应通过实验室检测进行相应确认。
  • 肾功能不全/衰竭:免疫球蛋白产品尤其是含蔗糖的产品静脉内用药时可能发生急性肾功能不全/衰竭、急性肾小管坏死、近端肾小管病、渗透性肾病和死亡。应确保患者在输注前没有低血容量。对于因基础肾功能不全或易患急性肾功能衰竭而处于风险中的患者,应在启动治疗之前及治疗全程评估肾功能,并考虑少量多次给药。如果肾功能恶化,应考虑停药。
  • 局部感染扩散:不要将HYQVIA注入感染部位或感染部位周围,因为局部感染可能有扩散的风险。
  • 输液相关急性肺损伤:免疫球蛋白静脉给药时可能会发生非心源性肺水肿。患者应监测肺部不良反应。若有疑诊,应相应检测产品及患者血清中有无抗中性粒细胞和抗HLA抗体。可在具备充分通气支持的情况下采用氧疗进行处治。
  • 传染性病原体:由于HYQVIA由人类血浆制成,它可能具有传播传染性病原体(例如病毒、其他病原体)的风险。尚无任何病毒性疾病或变异型克雅氏病(vCJD)传播病例与HYQVIA相关。
  • 干扰实验室检测:由于被动转移抗体,可能会出现假阳性血清学检测结果和某些检测读数,可能会导致误读。

不良相互作用

>5%的临床试验患者中观察到的最常见不良反应有:局部不良反应,包括疼痛、红斑、水肿和瘙痒,以及全身性不良反应,包括头痛、产生针对重组人类透明质酸酶的抗体(rHuPH20)、疲乏、恶心、发烧和呕吐。 

药物相互作用

抗体的被动转移可能会短暂干扰对活性减毒病毒疫苗(例如麻疹、腮腺炎、风疹和水痘)的免疫应答。 

 

医疗信息

本新闻稿所提到的产品可能并未在所有国家上市,或可能以不同的商标进行销售,或用于不同的病症,或采用不同的剂量,或拥有不同的效力。本文中所包含的任何信息都不应被看作是任何处方药的申请、推广或广告,包括那些正在研制的药物。 

_______________________________________  
1
 Eftimov F, et al. Cochrane Database Syst Rev. 2013;12:CD001797.  
2 Dalakas MC. Nat Rev Neurol. 2011;7(9):507–17.  
3 Köller H, et al. N Engl J Med. 2005;352(13):1343–56.  
4 Elovaara I, et al. Eur J Neurol. 2008;15(9):893–908.  
5 Jacob S, Rajabally YA. Curr Neuropharmacol. 2009;7(4):337–42.  
6 Nimmerjahn F, Ravetch JV. J Exp Med. 2007;204(1):11–5.  
7 Takeda data on file.  
8 Guptill JT, et al. Muscle Nerve. 2014;50(1):47‐51.  
9 Broers MC, et al. Neuroepidemiology. 2019;52(3‐4):161‐172.  
10 Chaudhary UJ and Rajabally YA. J Neurol. 2021;268(4):1366‐1373.

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topicList=[TopicDto(id=4704, encryptionId=f88a4e047f, topicName=CID)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=570f404, createdName=xlxchina, createdTime=Wed Feb 01 13:28:23 CST 2023, time=2023-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911296, encodeId=33e919112968f, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Tue Feb 21 22:28:23 CST 2023, time=2023-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491445, encodeId=c9d314914457d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1516421, encodeId=1df415164211f, content=<a href='/topic/show?id=8160852e55c' target=_blank style='color:#2F92EE;'>#脱髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85275, encryptionId=8160852e55c, topicName=脱髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f3ba10959947, createdName=1696533704_45270457, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517291, encodeId=1591151e29191, content=<a href='/topic/show?id=a0176333892' target=_blank style='color:#2F92EE;'>#武田#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63338, encryptionId=a0176333892, topicName=武田)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6da11069119, createdName=12498f17m69暂无昵称, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1595538, encodeId=dc461595538e5, content=<a href='/topic/show?id=371912932d' target=_blank style='color:#2F92EE;'>#3期临床试验#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1293, encryptionId=371912932d, topicName=3期临床试验)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79cd18252620, createdName=slcumt, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234782, encodeId=d9631234e82af, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1bdd5596550, createdName=清漩, createdTime=Tue Jul 26 08:31:38 CST 2022, time=2022-07-26, status=1, ipAttribution=)]
    2022-12-23 jml2009
  3. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Dec 23 10:28:23 CST 2022, time=2022-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1756310, encodeId=82671e56310ca, content=<a href='/topic/show?id=7414e433393' target=_blank style='color:#2F92EE;'>#神经根#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74333, encryptionId=7414e433393, topicName=神经根)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=806637100031, createdName=dzx0922901, createdTime=Wed Apr 12 05:28:23 CST 2023, time=2023-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991647, encodeId=a373199164eab, content=<a href='/topic/show?id=f88a4e047f' target=_blank style='color:#2F92EE;'>#CID#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4704, encryptionId=f88a4e047f, topicName=CID)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=570f404, createdName=xlxchina, createdTime=Wed Feb 01 13:28:23 CST 2023, time=2023-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911296, encodeId=33e919112968f, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Tue Feb 21 22:28:23 CST 2023, time=2023-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491445, encodeId=c9d314914457d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, 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Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234782, encodeId=d9631234e82af, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1bdd5596550, createdName=清漩, createdTime=Tue Jul 26 08:31:38 CST 2022, time=2022-07-26, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Dec 23 10:28:23 CST 2022, time=2022-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1756310, encodeId=82671e56310ca, content=<a href='/topic/show?id=7414e433393' target=_blank style='color:#2F92EE;'>#神经根#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74333, encryptionId=7414e433393, topicName=神经根)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=806637100031, createdName=dzx0922901, createdTime=Wed Apr 12 05:28:23 CST 2023, time=2023-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991647, encodeId=a373199164eab, content=<a href='/topic/show?id=f88a4e047f' target=_blank style='color:#2F92EE;'>#CID#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4704, encryptionId=f88a4e047f, topicName=CID)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=570f404, createdName=xlxchina, createdTime=Wed Feb 01 13:28:23 CST 2023, time=2023-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911296, encodeId=33e919112968f, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Tue Feb 21 22:28:23 CST 2023, time=2023-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491445, encodeId=c9d314914457d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1516421, encodeId=1df415164211f, content=<a href='/topic/show?id=8160852e55c' target=_blank style='color:#2F92EE;'>#脱髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85275, encryptionId=8160852e55c, topicName=脱髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f3ba10959947, createdName=1696533704_45270457, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517291, encodeId=1591151e29191, content=<a href='/topic/show?id=a0176333892' target=_blank style='color:#2F92EE;'>#武田#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63338, encryptionId=a0176333892, topicName=武田)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6da11069119, createdName=12498f17m69暂无昵称, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1595538, encodeId=dc461595538e5, content=<a href='/topic/show?id=371912932d' target=_blank style='color:#2F92EE;'>#3期临床试验#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1293, encryptionId=371912932d, topicName=3期临床试验)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79cd18252620, createdName=slcumt, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234782, encodeId=d9631234e82af, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1bdd5596550, createdName=清漩, createdTime=Tue Jul 26 08:31:38 CST 2022, time=2022-07-26, status=1, ipAttribution=)]
    2023-02-01 xlxchina
  5. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, 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encodeId=1591151e29191, content=<a href='/topic/show?id=a0176333892' target=_blank style='color:#2F92EE;'>#武田#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63338, encryptionId=a0176333892, topicName=武田)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6da11069119, createdName=12498f17m69暂无昵称, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1595538, encodeId=dc461595538e5, content=<a href='/topic/show?id=371912932d' target=_blank style='color:#2F92EE;'>#3期临床试验#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1293, encryptionId=371912932d, topicName=3期临床试验)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79cd18252620, createdName=slcumt, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234782, encodeId=d9631234e82af, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1bdd5596550, createdName=清漩, createdTime=Tue Jul 26 08:31:38 CST 2022, time=2022-07-26, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Dec 23 10:28:23 CST 2022, time=2022-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1756310, encodeId=82671e56310ca, content=<a href='/topic/show?id=7414e433393' target=_blank style='color:#2F92EE;'>#神经根#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74333, encryptionId=7414e433393, topicName=神经根)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=806637100031, createdName=dzx0922901, createdTime=Wed Apr 12 05:28:23 CST 2023, time=2023-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991647, encodeId=a373199164eab, content=<a href='/topic/show?id=f88a4e047f' target=_blank style='color:#2F92EE;'>#CID#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4704, encryptionId=f88a4e047f, topicName=CID)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=570f404, createdName=xlxchina, createdTime=Wed Feb 01 13:28:23 CST 2023, time=2023-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911296, encodeId=33e919112968f, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Tue Feb 21 22:28:23 CST 2023, time=2023-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491445, encodeId=c9d314914457d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1516421, encodeId=1df415164211f, content=<a href='/topic/show?id=8160852e55c' target=_blank style='color:#2F92EE;'>#脱髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85275, encryptionId=8160852e55c, topicName=脱髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f3ba10959947, createdName=1696533704_45270457, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517291, encodeId=1591151e29191, content=<a href='/topic/show?id=a0176333892' target=_blank style='color:#2F92EE;'>#武田#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63338, encryptionId=a0176333892, topicName=武田)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6da11069119, createdName=12498f17m69暂无昵称, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1595538, encodeId=dc461595538e5, content=<a href='/topic/show?id=371912932d' target=_blank style='color:#2F92EE;'>#3期临床试验#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1293, encryptionId=371912932d, topicName=3期临床试验)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79cd18252620, createdName=slcumt, createdTime=Wed Jul 27 10:28:23 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234782, encodeId=d9631234e82af, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1bdd5596550, createdName=清漩, createdTime=Tue Jul 26 08:31:38 CST 2022, time=2022-07-26, status=1, ipAttribution=)]
    2022-07-27 axin012
  7. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, 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  8. [GetPortalCommentsPageByObjectIdResponse(id=1755099, encodeId=edb91e55099d8, content=<a href='/topic/show?id=d1011021391e' target=_blank style='color:#2F92EE;'>#髓鞘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102139, encryptionId=d1011021391e, topicName=髓鞘)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f28436833652, createdName=xiaogang329, createdTime=Tue Aug 23 12:28:23 CST 2022, time=2022-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890395, encodeId=7772189039556, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, 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  9. 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