Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France.
Aliment Pharmacol Ther. 2017 Jan;45(2):276-282. doi: 10.1111/apt.13862. Epub 2016 Nov 16.
Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking.
To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients.
The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as 'sero-reversal', elevation of drug levels and regained clinical response were the sought outcomes.
Twenty-three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero-reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero-reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics.
In almost half of inflammatory bowel disease patients developing anti-adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico-biological response. However, these observations need to be confirmed with larger studies.
抗阿达木单抗抗体（AAA）与临床应答丧失（LOR）相关。已经证实，添加免疫调节剂可逆转英夫利昔单抗单药治疗的免疫原性，并恢复应答。阿达木单抗缺乏类似的数据。
研究免疫调节剂添加对阿达木单抗治疗患者出现 AAA 和 LOR 的影响。
回顾了三个三级医疗中心的数据库，以确定在阿达木单抗单药治疗期间出现 AAA 导致 LOR 并接受免疫调节剂作为挽救性联合治疗的患者。所有血清均使用先前描述的 ELISA 检测进行前瞻性分析。临床应答通过适当的临床评分确定。寻求的结果是消除 AAA，称为“血清学逆转”、药物水平升高和恢复临床应答。
23 名患者（21 名克罗恩病，2 名溃疡性结肠炎）出现 AAA 伴随后续 LOR，并随后开处免疫调节剂作为挽救治疗（硫唑嘌呤 n = 14，甲氨蝶呤 n = 9）。11 名患者（48%）发生血清学逆转，AAA 逐渐消除，药物谷浓度增加，临床应答恢复（血清学逆转中位时间为 5 个月）。在 12 名患者（52%）中，免疫原性和应答丧失无法逆转。在使用的免疫调节剂类型或基线临床特征方面，应答者和无应答者之间没有差异。
在近一半出现抗阿达木单抗抗体和应答丧失的炎症性肠病患者中，通过添加免疫调节剂治疗，逐渐逆转阿达木单抗的既定免疫原性，可恢复临床和生物学应答。然而，这些观察结果需要通过更大的研究来证实。
