Could galcanezumab modulate inflammatory cytokines? A single-centre exploratory study.

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Migraine is a disabling neurological disorder with complex pathophysiology.
• Calcitonin gene-related peptide (CGRP) is implicated, but alternative mechanisms like neuroinflammation involving cytokines are suggested.
• Distinct cytokine profiles may differentiate migraine subtypes and influence treatment response.

Purpose of the Study:

• To compare plasma cytokine profiles in episodic migraine (EM), chronic migraine (CM), and healthy controls (HC).
• To investigate the effect of galcanezumab on cytokine levels in EM patients.

Main Methods:

• Prospective pilot study involving 17 EM, 18 CM patients, and 17 HC.
• Plasma cytokine levels (IFN-γ, IL-1β, IL-10, IL-6, TNF-α) measured via multiplex immunoassay during the interictal phase.
• EM patients receiving galcanezumab had samples collected at baseline, Cmax (5 days), and drug half-life (27 days).

Main Results:

• EM patients exhibited elevated interictal levels of IFN-γ, IL-1β, IL-6, and IL-10 compared to CM and HC.
• Galcanezumab treatment led to a significant decrease in IFN-γ, IL-1β, IL-10, and TNF-α at Cmax, but not IL-6.
• Cytokine levels showed a transient reduction during the first month of galcanezumab therapy.

Conclusions:

• Distinct cytokine profiles are associated with EM and CM.
• Galcanezumab treatment transiently reduces both pro- and anti-inflammatory cytokines.
• Findings support the role of CGRP in modulating inflammatory pathways in migraine pathophysiology.