Matching-adjusted indirect comparison of pneumococcal vaccines V114 and PCV20.

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-naive 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.