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有遲發潰瘍性結腸炎年長者比年輕病患更可能在一年時經歷不用類固醇的緩解
作者：Jacqueline A. Hart, MD  
出處：WebMD醫學新聞

　　April 14, 2010 — 根據線上發表於4月5日臨床腸胃病學與肝臟病學(Clinical Gastroenterology and Hepatology)期刊的回溯研究，診斷有潰瘍性結腸炎(ulcerative colitis，UC)的50歲以上病患，曾有抽菸的比率較高，但是比18-30歲的UC病患更可能在診斷一年後達到不用類固醇的緩解程度。
　　
　　第一作者、紐約市西奈山醫學院胃腸科Christina Y. Ha醫師等人解釋，UC的流行病學研究發現，該疾病的發生呈現一個雙峰分布，第一波高峰出現在30歲左右，略小的第二波高峰則是在50-80歲時，因此，即便人口老化且遲發型UC發生率增加，關於年紀對早發或遲發UC成人患者出現疾病、臨床病程、治療反應之影響的瞭解有限。
　　
　　由於UC的風險因素和免疫功能因年紀而異，作者們試圖確認診斷UC時為年輕或年長者，在臨床結果或疾病行為上的差異。
　　
　　使用回溯型世代設計，分析2001至2008年間在華盛頓大學發炎性腸道疾病(inflammatory bowel disease，IBD)門診接受治療的295名病患的：
　　* IBD相關藥物之使用
　　* 使用蒙特婁分類系統和修訂版Truelove-Witts嚴重度指數，評估診斷時的疾病範圍與嚴重度；
　　* 因結腸炎加劇而住院
　　* 選擇性結腸切除術和緊急結腸切除術
　　* 診斷一年內的死亡率；以及
　　* 主要臨床終點是，疾病發生後一年，不用類固醇的緩解。
　　
　　這兩組的設定，早發組定義為診斷時的年紀在18-30歲(n = 155人)，遲發組是在50歲以上新發現診斷(n = 140人)，蒐集其他的人口統計學資料且評估性別、抽菸史、家族UC病史之間的差異。
　　
　　在一年時，相較於較年輕的病患，遲發型UC病患較多達到不用類固醇的臨床緩解(64% vs 49%；P = .01)。兩組的緩解率在性別方面沒有差異，早發型UC病患傾向有較多的結腸切除術件數；不過，差異未達統計上的顯著程度，住院率的差異也沒有(n = 57 vs n = 66；P = .09)，除非考量其中較年長的小組，特別的是，相較於早發型UC病患，UC發生在60歲以上者，比較可能因為結腸炎加劇而住院(P = .03)。
　　
　　就疾病第一年的整體藥物使用情況而言，兩組之間沒有統計上的顯著差異，遲發型UC病患的5-aminosalicylate (5-ASA)使用率略高，免疫調節劑和infliximab的使用比率也相似，多數病患在疾病第一年需要口服或靜脈注射類固醇(63.4%的早發型病患以及將近68%的遲發型病患)，處方免疫調節劑(但不是infliximab或5-ASA)者之中，遲發型病患在一年時比早發型有較多人達到不用類固醇的緩解(分別是43.9% 和17.5%；P = .016)，在診斷時需要類固醇者之中，遲發型病患在一年時比早發型有較高比率可以停止使用類固醇且維持不用(P = .019)。
　　
　　如同作者們指出的，早發型UC看來有一種遺傳上的組成，而遲發型UC比較可能是免疫系統和腸道障礙功能的年紀相關改變所致，也可能是其他環境因素如抽菸史的影響。研究結果支持這幾個主張，也增加了對有相似結果之早期研究的信心。遲發型組有將近52%是曾經抽菸者，較年輕病患組則有13.5%是戒菸者(P < .001)，30歲以下病患有21%以上有家族IBD病，年長組則有10.8% (P = .008)。
　　
　　這個試驗的強度包括使用大型、定義良好的研究族群，直接比較遲發型和早發型UC，研究限制包括，回溯型設計；研究對象是三級照護中心病患，病情可能較嚴重；中心內醫師治療決策的差異性；採信病歷上大腸鏡檢查發現的描述與準確度；缺乏內視鏡檢查規範來證實一年時的臨床緩解。
　　
　　研究者寫道，隨著人口老化，診斷為遲發型UC的病患人數會繼續增加，年長UC病患的治療通常因為併用藥物與共病症而有所挑戰。因為年長病患的類固醇相關併發症風險增加，我們的研究強調，及早開始使用5-ASA進行維持治療，並考慮免疫調節治療的重要性。
　　
　　作者們呼籲對遲發型UC病患的藥物治療反應繼續進行研究，後續研究也要注意區別遲發型和早發型UC的環境因素與遺傳因素。
　　
　　研究作者們皆宣告沒有相關財務關係。
　　
　　Clin Gastroenterol Hepatol. 線上發表於2010年4月5日。


Older Adults With Late-Onset Ulcerative Colitis More Likely to Experience Steroid-Free Remission at 1 Year Than Younger Patients

By Jacqueline A. Hart, MD
Medscape Medical News

April 14, 2010 — Adults diagnosed with ulcerative colitis (UC) at age 50 years or older had a higher incidence of former tobacco use but were more likely than patients with UC between the ages of 18 and 30 years to be in steroid-free remission at 1 year after diagnosis, according to a retrospective study published online April 5 in Clinical Gastroenterology and Hepatology.

"Epidemiologic studies of [UC] reveal a bimodal distribution of disease onset with an initial peak in the third decade and a smaller second peak between the ages of 50 and 80," explain lead author Christina Y. Ha, MD, from the Division of Gastroenterology, Mount Sinai School of Medicine, New York City, and colleagues. Despite an aging population and, therefore, a rise in incidence of late-onset UC, little is understood about "the influence of age on the presentation, clinical course, and therapeutic response of patients with [early vs late] adult-onset [UC]."

Because risk factors for UC and immune function vary depending on age, the authors "sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later vs earlier stages of adulthood."

Using a retrospective cohort design, 295 patients treated at an inflammatory bowel disease (IBD) clinic at Washington University in St. Louis between 2001 and 2008 were analyzed for

IBD-related medication use;
disease extent and severity at the time of diagnosis, evaluated by the Montreal classification system and the modified Truelove and Witts Severity Index;
hospitalizations for colitis flares;
elective and emergent colectomies;
mortality rate within the first year of diagnosis; and
primary clinical endpoint of steroid-free remission 1 year after disease onset.
The 2 groups compared were defined as early onset, diagnosed between the ages of 18 and 30 years (n = 155), and late onset, newly diagnosed at age 50 years or older (n = 140). Additional demographic data gathered and differences assessed included sex, smoking history, and family history of UC.

More patients with late-onset UC achieved steroid-free clinical remission compared with younger patients (64% vs 49%; P = .01) at 1 year. There were no sex differences in rates of remission between the 2 groups. There was a trend toward greater numbers of colectomies for those with early-onset UC; however, the difference was not statistically significant, nor were differences in hospitalization rates (n = 57 vs n = 66; P = .09) until a subset of the older group was considered. Specifically, those with UC onset at age 60 years or older were more likely to be hospitalized for colitis flares compared with patients with early-onset UC (P = .03).

In terms of overall medication use during the first year of disease, there were no statistical differences between the 2 groups, with slightly higher rates of 5-aminosalicylate (5-ASA) use in the patients with late-onset UC, similar rates of immunomodulator and infliximab use, and most patients needing oral or intravenous steroids within the first year of disease (63.4% of early-onset and nearly 68% of late-onset patients). Of those prescribed immunomodulators (but not infliximab or 5-ASA), a greater number of late- vs early-onset patients achieved steroid-free remission at 1 year (43.9% vs 17.5%, respectively; P = .016). Of those who required steroids at the time of diagnosis, a higher percentage of late- vs early-onset UC adults were able to wean off of the steroids and remain steroid free at 1 year (P = .019).

As the authors note, early-onset UC appears to have a genetic component, whereas late-onset UC is more attributable to age-related changes in the immune system and intestinal barrier function, as well as other environmental influences such as former smoking history. The study results support each of these assertions and lend credence to earlier trials with similar outcomes. Nearly 52% of the late-onset group were former smokers compared with 13.5% of ex-smokers in the younger patients (P < .001). More than 21% of patients aged 30 years and younger had a family history of IBD compared with 10.8% in the older group (P = .008).

Strengths of this trial include use of a large, well-defined study population and direct comparison of patients with late- vs early-onset UC. Limitations include the retrospective design; use of a tertiary-care center, in which patients may be sicker; variability of treatment decisions by physicians at the center; reliance on medical records for accuracy and descriptions of colonoscopy findings; and lack of endoscopic criteria to corroborate clinical remission at 1 year.

"The number of patients diagnosed with late-onset UC will likely continue to increase with the aging of the population," the investigators write. "Treatment of the older UC patient is often challenged by concomitant medication use and comorbid conditions.... Given that older patients are at increased risk for steroid related complications, [our] work underscores the importance of early initiation of maintenance therapy with 5-ASA and consideration of immunomodulator therapy."

The authors go on to call for "additional research focusing on the therapeutic response to these medications in the late-onset UC population," as well as "further investigation into the environmental and genetic factors that differentiate late- versus early-onset UC."

The study authors have disclosed no relevant financial relationships.

Clin Gastroenterol Hepatol. Published online April 5, 2010.