Unlike other autoimmune blistering diseases, eosinophils appear to play a significant role in the pathophysiology of Bullous Pemphigoid (BP) as lesions have been shown to contain eosinophil-rich infiltrates in the upper dermis. Furthermore, successful therapy of BP has been demonstrated with the use of anti-IgE antibody treatment, an important aspect as eosinophils from BP patients express the high-affinity IgE receptor FcƐRI.¹ The role of eotaxin in the recruitment of eosinophils into inflammatory sites has been described and the specific eotaxin receptor, CCR3, has been documented to be expressed on eosinophils, basophils, and Th2 cells. Eotaxin-1 binds CCR3 on eosinophils and ultimately drives chemotaxis and degranulation. The expression of both eotaxin-1 and CCR3 in lesional skin from patients with active BP and control subjects affected with pemphigus vulgaris (PV) was analyzed in a study.² A strong immunostaining for eotaxin-1 and CCR3 was observed in BP skin specimens and eotaxin serum levels were significantly higher in BP patients when compared to healthy donors (P=0.003) and PV patients (P=0.01).

All these results confirm the role of eotaxin-1 in the recruitment of activated cells at inflammatory sites during BP and the expression of CCR3 further supports the involvement of Th2 cells in the pathogenesis of this disease.

Bertilimumab is an anti-eotaxin-1 antibody with a high affinity and specificity for eotaxin-1. It blocks eotaxin-mediated chemotaxis and inhibits eotaxin-1-induced eosinophil conformational change.

To evaluate the safety, efficacy, and pharmacodynamic effect of bertilimumab in patients with BP.

Type of study (NCT02226146)³

• Phase 2A
• Interventional
• Open-label.

Patient populations

• ≥60 years
• Karnofsky performance status >60%
• Newly diagnosed or resistant to steroid taper
• Moderate-to-extensive BP.

Primary Outcome Measure

• Safety.

Secondary Outcome Measure

Change in Bullous Pemphigoid Disease Area Index (BPDAI) score.

Drug/Procedures used

• Three doses of 10 mg/kg of bertilimumab intravenously injected every 2 weeks
  • Infused over a period of 30 minutes
  • Concomitant 30 mg of prednisone daily with an end taper to 2.5 mg, based on clinical response.

Primary endpoints

• Bertilimumab was well-tolerated with only 4 adverse events (AEs) reported in 3 subjects, all of which reversed.
• All AEs were mild in intensity, 1 was serious but was believed to be unrelated to the drug (peripheral vascular disease exacerbation requiring hospitalization).

Secondary endpoints

• There was an 85% reduction in the BPDAI total activity index (P=0.0096) with all patients demonstrating a >50% improvement and 4 out of 6 patients demonstrating >90% improvement.
• Additionally, with the tapering of prednisone, 26 mg (0.3 mg/kg) tapered to a mean of 9 mg (0.1 mg/kg) by the last assessment (P=0.0145), subjects were spared more than 2,500 mg of prednisone over an 84-day period.