Matching-adjusted indirect comparison of pneumococcal vaccines V114 and PCV20

ABSTRACT

Background

V114 (15-valent pneumococcal conjugate vaccine [PCV15]) and a 20-valent PCV (PCV20) are approved for adults (≥18 years) in the United States. We present methodologies to indirectly compare immune responses to V114 versus PCV20.

Research design and methods

Indirect treatment comparison and matching-adjusted indirect comparison (MAIC) were performed to estimate opsonophagocytic activity (OPA) geometric mean titer (GMT) ratios of V114/PCV20 at 30 days post-vaccination with PCV13 as common comparator for 13 serotypes (STs) shared with a 13-valent PCV (PCV13) among pneumococcal vaccine-naïve adults aged ≥60 years. Data from three V114 studies were pooled (V114, N = 2,196; PCV13, N = 843). In the MAIC analysis, data were reweighted, matching participant age and sex in NCT03760146 (PCV20, N = 1,507; PCV13, N = 1,490).

Results

The lower bound of V114/PCV20 OPA GMT ratio for all PCV13 STs is greater than the prespecified  0.5 non-inferiority margin and those for five PCV13 STs (3, 6A, 6B, 18C, and 23F) are greater than the prespecified 1.2 superiority margin. V114 was associated with 77% greater OPA GMT for ST3 versus PCV20.

Conclusion

V114 was non-inferior to PCV20 for all PCV13 STs and statistically superior for five PCV13 STs.

KEYWORDS:

• Immunogenicity
• matching-adjusted indirect comparison
• pneumococcal conjugate vaccine
• pneumococcal disease
• V114
• PCV15

Acknowledgments

The authors would like to thank Yirong Cao for contribution towards designing and writing of the statistical programs for these analyses. Medical writing support, including assisting authors with the development of the initial draft and incorporation of comments, was provided by Rachel Wright, PhD, of Scion, London, and Salini Mohanty, DrPH, MPH, of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and editorial support was provided by Ian Norton, PhD, of Scion, London, according to Good Publication Practice guidelines.

Disclosure statement

S Mt-Isa, L Abderhalden, L Musey, and T Weiss are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

L Abderhalden: analysis and interpretation of data, preparation of the manuscript; review of the manuscript. S Mt-Isa, L Musey, T Weiss: Indirect treatment comparison study conception, authoring of the study protocol and analysis and interpretation of data, preparation of the manuscript; review of the manuscript.

Additional information

Funding

This paper was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.