Milella Giammarco, Sozzo Marco, Lasorella Piergiorgio, Scannicchio Stefania, Carlone Sebastiano, Fornaro Marco, Defazio Giovanni
Department of Translational Biomedicine and Neurosciences (DiBraiN), Neurology Unit, University of Bari Aldo Moro, Bari, Italy.
Neurology Unit, AOU Consorziale Policlinico, University of Bari, Bari, Italy.
J Neurol. 2025 May 30;272(6):432. doi: 10.1007/s00415-025-13175-0.
There is growing evidence that anti-TNF-α therapies may trigger immune-mediated polyneuropathies. However, the clinical spectrum, therapeutic strategies, and long-term outcomes remain insufficiently defined. This systematic review aims to address these gaps by collecting published case-reports and describing two additional cases of anti-TNF-α-induced neuropathy.
A total of 99 cases from the literature and two from our center were included (n = 101). Clinical, neurophysiological, therapeutic, and outcome data were summarized. Predictors of poor neurological outcomes were identified using univariate and multivariate logistic regression.
Ninety percent of neuropathies typically developed within the first 24 months of treatment (median: 6 (IQR: 3-14) months), with Infliximab as the most frequently implicated agent (63.4%). Motor impairment, either isolated (29.7%) or with sensory symptoms (55.4%), was the predominant presentation. Neurophysiological studies showed conduction blocks (41%) or demyelination (39%). TNF-α therapy was discontinued in 94.8% of cases, and rescue immunotherapy was used in 73%. Complete recovery occurred in 39.6%, while 31.7% developed a chronic inflammatory demyelinating polyneuropathy-like phenotype. Univariate analysis identified sensory-motor involvement, demyelination, and conduction blocks as predictors of poor outcome; multivariate analysis confirmed sensory-motor involvement as an independent predictor (OR = 5.14; 95% CI: 1.24-21.34; p = 0.024). Symptom recurrence was evident in 7 re-exposed patients, while no relapse was observed in 2 patients who underwent dose reduction or different anti-TNF-α drug.
Anti-TNF-α therapy can induce neuropathies characterized predominantly by motor symptoms and demyelinating features, frequently resulting in chronic neurological impairment despite drug withdrawn and immunomodulatory therapy. Drug rechallenge should be approached cautiously, and close monitoring is warranted if rechallenge is considered.
越来越多的证据表明，抗TNF-α疗法可能引发免疫介导的多发性神经病。然而，其临床谱、治疗策略和长期预后仍未得到充分界定。本系统评价旨在通过收集已发表的病例报告并描述另外两例抗TNF-α诱导的神经病病例来填补这些空白。
纳入了来自文献的99例病例和我们中心的2例病例（n = 101）。总结了临床、神经生理学、治疗和预后数据。使用单变量和多变量逻辑回归确定神经预后不良的预测因素。
90%的神经病通常在治疗的前24个月内发生（中位数：6（四分位间距：3 - 14）个月），英夫利昔单抗是最常涉及的药物（63.4%）。运动障碍，无论是单独出现（29.7%）还是伴有感觉症状（55.4%），是主要表现。神经生理学研究显示传导阻滞（41%）或脱髓鞘（39%）。94.8%的病例停用了TNF-α疗法，73%的病例使用了挽救性免疫疗法。39.6%的患者完全康复，而31.7%的患者发展为慢性炎症性脱髓鞘性多发性神经病样表型。单变量分析确定感觉运动受累、脱髓鞘和传导阻滞是预后不良的预测因素；多变量分析证实感觉运动受累是独立的预测因素（比值比 = 5.14；95%置信区间：1.24 - 21.34；p = 0.024）。7例再次暴露的患者出现症状复发，而2例接受剂量减少或改用不同抗TNF-α药物的患者未观察到复发。
抗TNF-α疗法可诱发主要以运动症状和脱髓鞘特征为特点的神经病，尽管停用药物并进行免疫调节治疗，但仍常导致慢性神经功能损害。药物再激发应谨慎进行，如果考虑再激发，有必要密切监测。
