חידושים אחרונים בטיפול במחלת מעי דלקתית בילדים

תוכן עניינים

• מבוא: האתגר הגובר של מחלת מעי דלקתית בילדים
• תגליות גנטיות במחלת מעי דלקתית בילדות
• דיאטה וטיפולים תזונתיים
• טיפולים תרופתיים
• אפשרויות טיפול חדשות
• יעדי טיפול בילדים עם מחלת מעי דלקתית
• מקור המידע

מבוא: האתגר הגובר של מחלת מעי דלקתית בילדים

קנדה מתמודדת עם אתגר משמעותי בתחום מחלת המעי הדלקתית בילדים (IBD), הכוללת מחלת קרוהן וקוליטיס כיבית. נתונים עדכניים מראים כי במדינתנו שיעורי התחלואה ב-IBD עם הופעה בילדות הם בין הגבוהים בעולם. כיום, כ-6,158 ילדים ובני נוער מתחת לגיל 18 חיים עם IBD, ורופאים מאבחנים 600-650 מקרים חדשים בילדים מתחת לגיל 16 מדי שנה.

באופן מדאיג, צפוי שמספר זה יעלה ל-8,079 ילדים נפגעים עד 2035. מקרים ילדותיים חדשים אלה מהווים כ-20%-10 מכלל החולים החדשים המאובחנים עם IBD. העלייה המשמעותית ביותר התרחשה בילדים מתחת לגיל 5, אם כי IBD עם הופעה בגיל ההתבגרות נותרה שכיחה יותר.

נתוני מנהל בריאות עדכניים הדגימו כי השכיחות הלאומית של IBD בכלל האוכלוסייה עמדה על 29.9 ל-100,000 איש (רווח בר-סמך 95%: 31.5 ,28.3) בשנת 2023. השכיחות עולה באוכלוסייה הילדים (שינוי שנתי ממוצע באחוזים: 1.67 ,0.82: 95%CI; 1.27%) למרות שכיחות יציבה במבוגרים (AAPC: 0.82 ,0.42-: 95%CI; 0.26%). עלייה זו בשכיחות הילדים היא תופעה עולמית שחוקרים בוחנים באופן פעיל.

הטיפול הנוכחי ב-IBD בילדים נע לכיוון גישת רפואה מותאמת אישית עם גישות ייחודיות ותקניות לגנטיקה, ריבוד סיכונים, זיהוי פנוטיפ מחלה, טיפולים תזונתיים ומתקדמים, ומרפאות מולטידיסציפליניות מיוחדות המבינות את האתגרים הייחודיים העומדים בפני חולים ילדים ומשפחותיהם עם אבחנת IBD.

תגליות גנטיות במחלת מעי דלקתית בילדות

מחקרים זיהו כי גורמים גנטיים, דיסביוזיס מיקרוביאלי (חוסר איזון בחיידקי המעי), ותגובות חיסוניות חריגות הקשורות לגורמים סביבתיים הם הגורמים העיקריים המשפיעים על התפתחות IBD. תרומת גורמים אלה ככל הנראה משתנה בהתאם לגיל הילד בעת האבחנה.

עם התקדמות ריצוף DNA מהדור הבא, רופאים יכולים כעת לאבחן גנטית ילדים עם IBD או מחלה דמוית IBD, המסווגת כ'IBD מונוגני'. חולים אלה הם בדרך כלל נדירים, סובלים ממחלה חמורה, ועמידים לטיפולים קונבנציונליים. סקירה שיטתית עדכנית אספה נתונים על מקרי IBD מונוגניים מבוססים, ומצאה שהפגם המונוגני המדווח ביותר היה קוליטיס של מסלול האיתות של אינטרלוקין (IL)-10, אחריו מחלת גרנולומטוזה כרונית (CGD), וחסר X-linked inhibitor of apoptosis (XIAP).

יש לציין כי יותר מ-10% ממקרי ה-IBD המונוגניים זוהו בקבוצות גיל מבוגרות, מה שמראה שצורות גנטיות אלה יכולות להתבטא מאוחר יותר בחיים. המחקר חשף כי 76% מהחולים עם IBD מונוגני פיתחו לפחות בעיה אחת מחוץ למעי במהלך מהלך מחלתם, עם טיפולים כולל ניתוח (27.1%), השתלת תאי גזע hematopoetic (23.1%), וטיפולים ביולוגיים (32.9%).

נתונים אלה מדגישים את האופי המגוון של מחלה מונוגנית, ורופאים צריכים לשקול בדיקה גנטית בכל החולים עם תסמיני מחלה יוצאי דופן, מחלה משמעותית מחוץ למעי, או אלה העמידים לטיפולים סטנדרטיים.

דיאטה וטיפולים תזונתיים

דיאטה מעורבת הן בהתפתחות והן באופי ההישנות/הפוגה של IBD, עם מחקר נרחב על תפקיד הדיאטה במצב זה. מחקרים אפידמיולוגיים תזונתיים רבים מדגימים קשרים מזיקים עם דפוסי דיאטה מערבית ויתרונות מגינים מדיאטה ים תיכונית. מחקרים בבעלי חיים קשרו מזונות אולטרה-מעובדים ותעשייתיים בהתפתחות דלקת.

עיקר הטיפול התזונתי ב-IBD בילדים היה הזנה אנטרלית בלעדית (EEN) עבור מחלת קרוהן - טיפול שבו חולים מקבלים רק פורמולת תזונה נוזלית למשך מספר שבועות. בקנדה, שיעורי השימוש ב-EEN דומים לאלה של קורטיקוסטרואידים לטיפול השראתי לפי נתונים מהרשת הקנדית ל-IBD בילדים.

EEN הדגימה יעילות במחקרים מרובים להשראת הפוגה וריפוי רירית, ולשיקום תזונתי. היא גם הראתה תועלת בילדים עם מחלה היצרות/חדירה או עם מסות דלקתיות. בחירת חולים נותרת חשובה להצלחת EEN, והיא עובדת בצורה הטובה ביותר כאשר היא נתמכת על ידי דיאטנית במרכז IBD עם ניסיון ב-EEN.

מחקרים מראים כי חולים עם מחלה בעיקר באילאום דיסטלי וחומרת מחלה קלה-בינונית נוטים יותר להגיב ל-EEN. מחקרים הבוחנים חתימות מיקרוביום וסמנים גנטיים הקשורים להצלחת EEN מתבצעים כעת, מה שעשוי לעזור לזהות אילו חולים ייהנו ביותר מטיפול זה.

טיפולים תזונתיים מרוצים הוצעו כדיאטות 'טיפול' ל-IBD, עם סקירת ספרות עדכנית שזיהתה יותר מ-24 דיאטות שונות המשמשות בניהול IBD. המוערכת ביותר היא דיאטת ההרחקה של מחלת קרוהן (CDED), המשלבת דיאטה מוגבלת עם הזנה אנטרלית חלקית (PEN) לאורך מספר שלבים של הגבלה הולכת ופוחתת.

הגבלות דיאטה התבססו על נתונים מבעלי חיים שבהם מוצרי מזון השפיעו על דלקת, דיסביוזיס, או חדירות מעי. שילוב זה היה דומה ל-EEN בהשראת הפוגה בשבוע 6 (75% בקבוצת CDED plus PEN לעומת 59% בקבוצת EEN), אך היו לו הצלחות מוגבלות בחולים עם מחלה חמורה, או אלה שאיבדו תגובה לתרופות ביולוגיות.

ברחבי מרכזים ילדותיים קנדיים, נותרת שונות משמעותית בהמלצות הדיאטה הסטנדרטיות ובאימוץ טיפולים תזונתיים עד שיופיעו נתונים חזקים יותר על דיאטות טיפוליות, מה שממשיך להיות מקור לתסכול עבור חולים ומשפחות המחפשות גישות תזונתיות לניהול IBD.

טיפולים תרופתיים

מספר הטיפולים התרופתיים שאושרו ל-IBD בחולים מבוגרים עלה במהירות בשנים האחרונות. עם זאת, אי-זמינות תרופות אלה לילדים הייתה בעיה גוברת עבור מטפלי IBD ילדותיים. יש פער זמן משמעותי לפני השלמת ניסויים אקראיים מבוקרים ילדותיים ומתן אישור רגולטורי, מה שמוביל לשימוש ממושך off-label של טיפולים חדשים בילדים.

טיפולים השראתיים מסורתיים כמו קורטיקוסטרואידים ו-EEN ממשיכים לשמש, אך השימוש באימונומודולטורים כמונותרפיה אחזקה, במיוחד במחלת קרוהן, ירד משמעותית כאשר רופאים עוברים להתמקד ב'טיפולים יעילים מוקדמים' כחלק מגישת treat-to-target. זה חשוב במיוחד מכיוון שרוב החולים הילדים מציגים מחלה בינונית-חמורה ונרחבת.

בקוליטיס כיבית, מחקר PROTECT הדגים כי חלק סביר מילדים המגיבים לסטרואידים מגיבים לטיפולי 5-ASA סטנדרטיים, אך בשבוע 52, רק 40% מהחולים הצליחו להמשיך טיפול 5-ASA ללא צורך בהגברת טיפול.

טיפולים נגד גורם נמק גידול (TNF) ממשיכים להיות הטיפולים האחזקה הנפוצים ביותר בילדים בשל זמינותם הממושכת ויעילותם, עם infliximab ו-adalimumab being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being 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being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being being

לאור הצרכים המורכבים הללו, קיימת הכרה גוברת כי יש לטפל בילדים עם מחלת מעי דלקתית (IBD) במרכזים מומחים רב-מקצועיים עם גישה לרופאים, אחיות מומחיות, דיאטנים ואנשי מקצוע בתחום בריאות הנפש בעלי מומחיות ב-IBD. גישה צוותית זו מסייעת להבטיח שילדים ומשפחותיהם יוכלו לקבל טיפול באיכות הגבוהה ביותר ל-IBD שלהם לאורך הילדות וההתבגרות.

מידע מקור

כותרת המאמר המקורי: עדכונים בטיפול במחלת מעי דלקתית בילדים

מחבר: Nicholas Carman, MBBS, FRACP

שיוך מוסדי: המרכז למחלת מעי דלקתית בסיק קידס, חטיבת גסטרואנטרולוגיה, הפטולוגיה ותזונה, בית החולים לילדים חולים (SickKids), טורונטו, אונטריו; אוניברסיטת טורונטו

פרסום: כרך 2, גיליון 1, אביב 2024

מאמר ידידותי זה למטופל מבוסס על מחקר שעבר ביקורת עמיתים ושומר על כל הממצאים המשמעותיים, הסטטיסטיקות והמידע הקליני מהפרסום המדעי המקורי.