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ウパダシチニブについて、巨細胞性動脈炎患者さんを対象とした第III相SELECT-GCA試験で良好な結果を示す


2024年5月22日
アッヴィ合同会社

アッヴィ、ウパダシチニブ(リンヴォック(R))について、巨細胞性動脈炎患者さんを対象とした第III相SELECT-GCA試験で良好な結果を示す

ー 第III相SELECT-GCA試験の結果から、投与12週時から投与52週時までの期間に寛解維持を達成した巨細胞性動脈炎(Giant Cell Arteritis:GCA)患者さんの割合は、ウパダシチニブ(リンヴォック(R)、15 mg)の投与と26週間のステロイド漸減投与を併用した患者さんでは46%であったのに対し、プラセボの投与と52週間のステロイド漸減投与を併用した患者さんでは29%と示される1
ー GCAにおける安全性プロファイルは既に承認されている適応症のものと概ね一致し、新たな安全性シグナルは認められず1
ー 本試験は、未だにアンメットニーズの高い免疫介在性疾患の患者さんに対する、新たな治療選択肢を開発してきたアッヴィの歴史を反映

イリノイ州ノースシカゴ、2024年4月18日(米国時間)-アッヴィ(NYSE: ABBV)は本日、SELECT-GCA試験(第III相、多施設共同、無作為化、二重盲検、プラセボ対照試験)で得られた良好なトップライン結果を発表しました。この結果により、成人巨細胞性動脈炎(GCA)患者さんに対して、ウパダシチニブ(リンヴォック(R)、15 mg、 1日1回)と26週間のステロイド漸減投与の併用により、主要評価項目である12週時から52週時までの期間の寛解維持aを達成したことが示されました。本試験において寛解維持を達成した患者さんの割合は、ウパダシチニブ15 mgと26週間のステロイド漸減投与を併用した患者さんでは46%であったのに対し、プラセボの投与と52週間のステロイド漸減投与を併用した患者さんでは29%でした(p=0.0019)1。

アッヴィのvice president兼global head of immunology clinical developmentであるKori Wallace, M.D., Ph.D.は、次のように述べています。「多くのGCA患者さんは、治療選択肢が限られている中、消耗性を引き起こす可能性がある症状に苦しみ続けています。今回の結果は、未だ大きなメディカルニーズがある疾患の新たな治療法を開発することにより、免疫介在性疾患の患者さんの生活改善を目指すという、当社の絶え間ない取り組みを示すものです」

GCAは自己免疫疾患であり、側頭動脈などの頭部の動脈、大動脈およびその他の大型・中型の動脈に炎症を引き起こします。一般的には、50歳以上に発症し、70~80歳の高齢者に最も多くみられます。女性の発症リスクが最も高く、本疾患により頭痛、顎痛および視力の変化や消失(突発性かつ永久的な視力消失を含む)を引き起こす可能性があります2。

今回の結果では、主要な副次評価項目も達成し、投与12週時から投与52週時までの期間に完全寛解維持bを達成した割合は、プラセボの投与と52週間のステロイド漸減投与を併用した患者さんと比較して、ウパダシチニブ15 mgと26週間のステロイド漸減投与を併用した患者さんの方が高いことが示されました(16%対37%、p<0.0001)1。投与52週時までの期間に1回以上の再燃が認められた患者さんの割合は、プラセボ群と比較してウパダシチニブ15 mg群の方が低いことが示されました(56%対34%、p<0.0014)1。また、本試験の結果から、ウパダシチニブ7.5 mgは主要評価項目もいずれの副次評価項目も到達していないことが認められました1。

ベルギーのガストハイスベルグ大学病院 一般内科医、ベルギーのルーベン・カトリック大学の内科教授、兼SELECT-GCA試験の治験責任医師であるDaniel Blockmans, M.D., Ph.D.は、次のように述べています。「今回の結果はリウマチ性疾患の治療におけるウパダシチニブの有効性および安全性プロファイルを裏付ける一連のエビデンスを強化するものであり、心強く思います。本試験の結果に基づき、ウパダシチニブはGCA患者さんにとって、初の経口治療選択肢となる可能性があります。GCAは、主に高齢の方が罹患する大型の動脈の炎症性疾患であり、これまでに承認され、ステロイドと一般的に併用されている治療法は1つしかありません3」

52週間のプラセボ対照期間において、ウパダシチニブ15 mgの安全性プロファイルは、既に承認されている適応症で認められたものと概ね一致していました1。本試験では、ウパダシチニブ15 mgの忍容性は総じて良好であり、新たな安全性シグナルは認められませんでした1。有害事象により投与中止となった患者さんの割合は、ウパダシチニブ15 mg群では15%、プラセボ群では21%でした1。本試験において、重篤な有害事象が認められた患者さんの割合は同程度でした(ウパダシチニブ15 mg群23%、プラセボ群21%)1。重篤な感染症が発現した割合は、ウパダシチニブ15 mg群で6%、プラセボ群で11%でした1。全体として、悪性腫瘍(非黒色腫皮膚がんを除く)が発生した患者さんおよび静脈血栓塞栓症と診断された患者さんの割合は、ウパダシチニブ15 mg群(それぞれ2%および3%)とプラセボ群(それぞれ2%および4%)で偏りはみられませんでした1。プラセボ群では主要心血管イベント(MACE)と判断された事象が2件認められたのに対し、ウパダシチニブ15 mg群では認められませんでした1。治験薬投与下で発現した死亡は4件報告され、2件がプラセボ群、2件がウパダシチニブ15 mg群でした1。ウパダシチニブ15 mg群の治験薬投与下で発現した死亡2件のうち、1件はCOVID-19によるものであり、もう1件は原因不明と判断されました1。

SELECT-GCA試験のすべての投与群における詳細な結果については、今後の医学学会での発表を予定しています。GCAに対するウパダシチニブの使用は承認されておらず、その安全性および有効性はこれまで規制当局により評価されていません。

a 寛解維持とは、投与12週時から投与52週時までの期間にGCAの徴候および症状がなく、該当する試験期間にわたって治験実施計画書に規定されたステロイド漸減投与計画を遵守していることと定義します。

b 完全寛解維持とは、投与12週時から投与52週時までの期間にGCAの徴候および症状がなく、治験実施計画書に規定されたステロイド漸減投与計画を遵守し、投与12週時から投与52週までの期間に赤血球沈降速度(ESR)および高感度C反応性タンパク質(hsCRP)がいずれも正常化していることと定義します。

SELECT-GCA試験について
SELECT-GCA(M16-852)試験は、巨細胞性動脈炎患者さん428名を対象に、ウパダシチニブの安全性および有効性を評価するよう設計された、第III相、多施設共同、無作為化、二重盲検、プラセボ対照試験です。本試験は2つの期間で構成されています。第1ピリオドでは、本リリースで報告されているように、ウパダシチニブと26週間のコルチコステロイド漸減投与の併用による有効性を、プラセボと52週間のコルチコステロイド漸減投与の併用と比較して評価しました。また、本試験ではこれらの患者さんにおけるウパダシチニブの安全性および忍容性を評価しました。第2ピリオドでは、第1ピリオドで寛解維持を達成した患者さんを対象に、寛解の維持を指標として、ウパダシチニブの投与継続と投与中止の安全性および有効性を比較します1。本試験の詳細な情報については、clinicaltrials.gov をご覧ください(NCT03725202)。

巨細胞性動脈炎について
巨細胞性動脈炎(GCA)は、側頭動脈炎とも知られており、三層の血管壁に肉芽腫性炎症を引き起こすことが特徴的な中型・大型の動脈の自己免疫疾患です。側頭動脈などの頭部の動脈のほか、大動脈などの大型の動脈を侵します2,4。GCAにより、頭痛、顎痛、視力の変化や消失(突発性かつ永久的な視力消失を含む)を引き起こす可能性があります2。欧米諸国の成人によくみられる血管炎2であり、発症率は、50歳以上、主に70~80歳の白人女性で最も高くなります。男性より女性の方が発症する可能性が高いものの、研究によると眼症状が生じる可能性は男性の方が高いことが示されています5。

ウパダシチニブ(リンヴォック(R))について
アッヴィの科学者が発見し開発したリンヴォックは、複数の免疫介在性炎症性疾患を対象に研究が進められている、JAK阻害薬です6,7。酵素および細胞アッセイにおいて、ウパダシチニブは、JAK-2、JAK-3およびTYK-2と比較してJAK-1に対しより強い阻害能力を示しました6。特定のJAK酵素の阻害が、治療効果と安全性にどのように関連しているかは現時点では明らかとなっていません。円形脱毛症、巨細胞性動脈炎、化膿性汗腺炎、高安動脈炎、全身性エリテマトーデス、白斑を対象とするウパダシチニブ(リンヴォック)の第III相試験が進行中です8-13。

リウマチ領域におけるアッヴィについて
アッヴィは 20 年以上にわたり、リウマチ性疾患とともに生きる患者さんの治療の向上に取り組んできました。革新的な治療を発見し、提供するという当社の長年の取り組みを主軸とし、有望な新たな経路や標的の理解を深める最先端科学を追求し、より多くのリウマチ性疾患の患者さんが治療目標を達成できるよう支援していきます。

アッヴィについて 
アッヴィのミッションは現在の深刻な健康課題を解決する革新的な医薬品の創製とソリューションの提供、そして未来に向けて医療上の困難な課題に挑むことです。一人ひとりの人生を豊かなものにするため次の主要領域に取り組んでいます。免疫疾患、がん、精神・神経疾患、アイケア、さらに美容医療関連のアラガン・エステティックスポートフォリオの製品・サービスです。アッヴィの詳細については、www.abbvie.comをご覧ください。X(旧Twitter)@abbvieFacebookLinkedInInstagramでも情報を公開しています。 

References:
1.AbbVie. Data on file ABVRRTI78418.
2.Ameer MA, Peterfy RJ, Khazaeni B. Giant cell arteritis. Updated August 8, 2023.
https://www.ncbi.nlm.nih.gov/books/NBK459376/
3.RoActemra 20 mg/mL concentrate for solution for infusion. SmPC Mar 2023
4.Weyand CM, Goronzy JJ. Immunology of Giant Cell Arteritis. Circ Res. 2023;132(2):238-250. doi:10.1161/CIRCRESAHA.122.322128
5.Giant Cell Arteritis. Arthritis Foundation. Available at: https://www.arthritis.org/diseases/giant-cellarteritis. Accessed April 11, 2024.
6.RINVOQ [Package Insert]. North Chicago, IL: AbbVie Inc.;2023.
7.Pipeline — Our Science I AbbVie. 2023. Available at: https://www.abbvie.com/ourscience/pipeline.html. Accessed April 17, 2024.
8.A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants with Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed April 9, 2024
9.A Study to Evaluate the Efficacy and Safety of Upadacitinib in Participants with Takaysu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/study/NCT04161898. Accessed April 9, 2024.
10.Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus (SELECT-SLE).
ClinicalTrials.gov. Available at: https://clinicaltrials.gov/study/NCT05843643. Accessed April
9, 2024.
11.A Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib in Adult and Adolescent Participants With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy (Step-Up HS). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/study/NCT05889182. Accessed April 9, 2024.
12.A Study To Assess Adverse Events and Effectiveness of Upadacitinib Oral Tablets in Adult and Adolescent Participants With Vitiligo (Viti-Up). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/study/NCT06118411. Accessed April 9, 2024.
13.A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata (Up-AA). ClinicalTrials.gov. Available at: https://clinicaltrials.govistudyNCT06012240. Accessed April 9, 2024.

 

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      Function: callBlock

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
      Line: 184
      Function: callBlock

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
      Line: 186
      Function: process

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
      Line: 156
      Function: process

      File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
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      Function: instanceBlock

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      Function: content_66f26b3cb92fa0_94546305

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
      Line: 114
      Function: getRenderedTemplateCode

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 217
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 386
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
      Line: 116
      Function: _subTemplateRender

      File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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      Function: endChild

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
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      Function: content_675a781dcbf339_49719938

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
      Line: 114
      Function: getRenderedTemplateCode

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 217
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 238
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 116
      Function: _execute

      File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
      Line: 45
      Function: fetch

      File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
      Line: 32
      Function: view

      File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
      Line: 292
      Function: require_once

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    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Undefined offset: 1

    Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php

    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 24
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
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