Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma

Publication date: Available online 23 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Sumita Khatri, Wendy Moore, Peter G. Gibson, Richard Leigh, Arnaud Bourdin, Jorge Maspero, Manuel Barros, Roland Buhl, Peter Howarth, Frank C. Albers, Eric S. Bradford, Martyn Gilson, Robert G. Price, Steven W. Yancey, Hector Ortega

Abstract

Background

Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials ≤12 months' duration; however, long-term data are lacking.

Objective

To evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA).

Methods

COLUMBA (NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (NCT01000506). Patients received 100mg subcutaneous mepolizumab every 4 weeks plus standard of care, until a protocol-defined stopping criterion was met. Safety endpoints included frequency of adverse events (AEs), serious AEs (SAEs), and AEs of special interest. Efficacy endpoints included annualized exacerbation rate, changes from baseline in Asthma Control Questionnaire (ACQ)-5 score, and blood eosinophil counts. Immunogenicity was also assessed.

Results

Overall, 347 patients were enrolled for an average of 3.5yrs (maximum: 4.5yrs; total exposure: 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate: 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced ≥1 on-treatment SAE; there were 6 deaths, none assessed as related to mepolizumab. For patients with ≥156 weeks enrollment, the exacerbation rate was 0.74 events/year (Weeks 0–156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first post-baseline assessment, the mean ACQ-5 score was reduced by 0.47 points and blood eosinophil counts by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies.

Conclusion

These data support the long-term safety and efficacy of mepolizumab in patients with SEA.

Clinical Implications

Following long-term use in patients with severe eosinophilic asthma, mepolizumab maintains clinical effectiveness and continues to demonstrate a favorable safety profile, with no evidence of inducing neutralizing antibodies.

Graphical abstract

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