Peripheral neuropathies associated with anti-tnf-α treatments: a systematic review and proposed recommendations

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by motor symptoms and demyelinating features, frequently resulting in chronic neurological impairment despite drug withdrawn and immunomodulatory therapy.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.