Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA.
Neuroscience Interdepartmental Program, University of California at Los Angeles, Los Angeles, CA, USA.
Am J Drug Alcohol Abuse. 2023 May 4;49(3):333-344. doi: 10.1080/00952990.2022.2124918. Epub 2022 Oct 25.
Inflammation is implicated in alcohol use disorder (AUD). Ibudilast, a neuroimmune modulator, shows promise for the treatment of AUD. Elevated inflammation, indicated by high levels of C-reactive protein (CRP), represents a possible subtype of AUD, which may be associated with treatment response to ibudilast. The current study evaluated CRP as a predictor of treatment response to ibudilast; hypothesizing that ibudilast would be more effective at reducing drinking and alcohol cue-reactivity in individuals with higher CRP levels. This is a secondary analysis of a clinical trial of ibudilast for AUD, which found that ibudilast reduced heavy drinking in individuals with AUD. Fifty-one individuals were randomized to receive ibudilast (n = 24 [16 M/8F]) or placebo (n = 27 [18 M/9F]) for two weeks. Participants provided blood samples at baseline to assess CRP levels, completed daily assessments of alcohol use, and an fMRI alcohol cue-reactivity task at study mid-point. Models tested the effects of medication, CRP levels, and their interaction on drinks per drinking day and alcohol cue-reactivity. There was a significant interaction between medication and CRP (F = 3.80, = .03), such that the ibudilast high CRP group had fewer drinks per drinking day compared to the ibudilast low CRP group. CRP moderated the effect of medication on brain activation in a cluster extending from the left inferior frontal gyrus to the right-dorsal striatum (Z = 4.55, < .001). This interaction was driven by attenuated cue-reactivity in the ibudilast high CRP group relative to the ibudilast low CRP and placebo high CRP groups. This study serves as an initial investigation into predictors of clinical response to ibudilast treatment and suggests that a baseline proinflammatory profile may enhance clinical efficacy.
炎症与酒精使用障碍（AUD）有关。神经免疫调节剂伊布地尔有望用于 AUD 的治疗。C 反应蛋白（CRP）水平升高表明存在炎症升高，这可能代表 AUD 的一种亚型，可能与伊布地尔的治疗反应有关。本研究评估了 CRP 作为伊布地尔治疗反应的预测因子；假设伊布地尔在 CRP 水平较高的个体中降低饮酒量和酒精线索反应的效果更好。这是一项伊布地尔治疗 AUD 的临床试验的二次分析，该试验发现伊布地尔可减少 AUD 患者的重度饮酒。51 名参与者被随机分为伊布地尔组（n = 24 [16 男/8 女]）或安慰剂组（n = 27 [18 男/9 女]），接受为期两周的治疗。参与者在基线时提供血液样本以评估 CRP 水平，完成每日饮酒量评估，并在研究中期进行 fMRI 酒精线索反应任务。模型测试了药物、CRP 水平及其相互作用对每日饮酒量和酒精线索反应的影响。药物和 CRP 之间存在显著的相互作用（F = 3.80，p =.03），即伊布地尔高 CRP 组的每日饮酒量较伊布地尔低 CRP 组少。CRP 调节了药物对从左额下回延伸至右背侧纹状体的脑区激活的影响（Z = 4.55，p <.001）。这种相互作用是由于伊布地尔高 CRP 组相对于伊布地尔低 CRP 组和安慰剂高 CRP 组的线索反应减弱所致。这项研究初步探讨了伊布地尔治疗临床反应的预测因子，并表明基线促炎特征可能增强临床疗效。
