Renna Sara, Cottone Mario, Orlando Ambrogio
Sara Renna, Mario Cottone, Ambrogio Orlando, Division of Internal Medicine, ''Villa Sofia-V. Cervello'' Hospital, 90146 Palermo, Italy.
World J Gastroenterol. 2014 Aug 7;20(29):9675-90. doi: 10.3748/wjg.v20.i29.9675.
Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn's disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.
许多安慰剂对照试验和荟萃分析评估了不同药物治疗炎症性肠病（IBD）的疗效，包括免疫抑制剂和生物制剂。它们适用于对皮质类固醇无反应的中度至重度疾病患者以及类固醇依赖患者，作为诱导和维持治疗。英夫利昔单抗以及环孢素在重度溃疡性结肠炎或对静脉注射皮质类固醇无反应的情况下被视为二线治疗。在评估硫唑嘌呤的疗效之前，应达到足够的剂量和疗程。甲氨蝶呤是克罗恩病患者的有效选择，但其使用仅限于对硫唑嘌呤不耐受或无反应的患者。甲氨蝶呤在溃疡性结肠炎中的使用证据不足。不建议炎症性肠病患者使用沙利度胺和霉酚酸酯，仅在所有其他治疗选择均失败时才考虑这些治疗方法。在对硫唑嘌呤难治的中度活动性溃疡性结肠炎患者中，使用他克莫司被认为是生物制剂的替代方案。在临床反应不完全的情况下，增加生物治疗的剂量或缩短给药间隔可能会有帮助。在抗肿瘤坏死因子α原发性失败的情况下，应考虑换用另一种药物。目前，联合治疗疗效的数据不足以让所有IBD患者都采用这种治疗策略。治疗的最终结果应以临床缓解并伴有黏膜愈合为准，而非临床反应。评估硫嘌呤甲基转移酶活性、硫嘌呤代谢物、生物制剂血清水平和抗生物制剂抗体的血清浓度可能有助于治疗管理，但尚未在临床实践中常规应用。长期接受免疫抑制剂和生物制剂治疗的患者应考虑淋巴瘤和皮肤恶性肿瘤高风险发展的证据。
