Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
Gut. 2019 Apr;68(4):623-632. doi: 10.1136/gutjnl-2017-315521. Epub 2018 Apr 4.
Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.
Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.
The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).
Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.
巯嘌呤类药物被用作溃疡性结肠炎（UC）的维持治疗，但这些药物是否会影响疾病的自然病程尚不清楚。我们旨在评估在开始治疗后 10 年内，巯嘌呤类药物对结肠切除术、住院、疾病程度进展和抗肿瘤坏死因子（TNF）治疗的影响。
纳入了在 1963 年至 2010 年间在厄勒布鲁大学医院（Örebro University Hospital）范围内诊断为 UC 的患者，这些患者开始使用巯嘌呤类药物（n=253）。为了克服适应证偏倚的风险，我们将因不良反应在 12 个月内停止治疗的患者（n=76）与继续治疗或因其他原因停药的患者（n=177）进行比较，并使用 Cox 回归评估长期结局，调整了潜在混杂因素的影响。
在耐受患者中，10 年内结肠切除术的累积概率为 19.5%，而不耐受患者为 29.0%（调整后的 HR 0.49；95%CI 0.21 至 0.73）。在耐受患者中，住院的概率为 34.0%，而在不耐受患者中为 56.2%（调整后的 HR 0.36；95%CI 0.23 至 0.56）。在耐受患者中，疾病程度进展的风险为 20.4%，而在不耐受患者中为 48.8%（调整后的 HR 0.47；95%CI 0.21 至 1.06）。在 10 年内，16.1%的耐受患者和 27.5%的不耐受患者接受了抗 TNF 治疗（调整后的 HR 0.49；95%CI 0.26 至 0.92）。
基于比较耐受和不耐受巯嘌呤类药物的患者的新方法，我们揭示了巯嘌呤类药物对 UC 的自然病程和长期结肠切除术率有深远的有益影响。
