Clinically reversible ustekinumab-induced encephalopathy: case report and review of the literature

Abstract

Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23 approved for the treatment of Crohn’s disease, has shown to be an effective therapy with a favourable safety profile. Clinical trials and real-world studies have reported very few neurological adverse events, including posterior reversible encephalopathy syndrome, idiopathic intracranial hypertension and headache. We describe the case of a 48-year-old man with Crohn’s disease who initiated treatment with ustekinumab on top of ongoing treatment with methotrexate 25 mg/week who presented with an acute-onset encephalopathy that rapidly evolved to severe tetraparesis and akinetic mutism, associated with extensive leukoencephalopathy and restricted diffusion on brain magnetic resonance imaging (MRI), 1 month after the second dose of ustekinumab. Comprehensive in-patient diagnostic testing ruled out vascular, demyelinating, metabolic, tumoral and infectious etiologies. Brain biopsy showed patchy infiltrates of foamy histiocytes with perivascular distribution, associated with edema, diffuse astrocytic gliosis and focal perivascular axonal destruction without demyelination, and ustekinumab-induced neurotoxicity was suspected. After drug discontinuation, the patient presented a complete clinical recovery despite the persistence of leukoencephalopathy. In conclusion, in an era in which biological therapies are continually evolving and expanding, knowledge about the potential neurotoxicity of these new therapies and their management becomes crucial. Although ustekinumab-induced encephalopathy is uncommon, the recognition of this potentially serious side effect is important because prompt withdrawal is associated with a favourable outcome. Whether methotrexate played an additional contributing role is currently unknown, but it is a factor that should be considered.

Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases

“…Monitoring of patients treated with ustekinumab for signs and symptoms of PRES and prompt administration of appropriate treatment and discontinuation of ustekinumab should be considered. 56 …”

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension

“…However, the incidence of hypertriglyceridemia was relatively high in our study (10.0–12.7% with tildrakizumab), possibly attributable to different baseline serum lipid levels in various studies. Compared to specific safety concerns associated with other biologic agents, such as reversible posterior leukoencephalopathy syndrome with ustekinumab, [ 19 ] neutropenia with secukinumab, [ 20 , 21 ] or ixekizumab, [ 22 , 23 ] and suicidal ideation and behavior with brodalumab, [ 24 ] tildrakizumab demonstrated a favorable safety profile, [ 25 ] even with long-term use, as evidenced by a pooled analysis with extensive 5-year follow-up. [ 6 ]…”