Matching-adjusted indirect comparison via a polynomial-based non-linear optimization method.

Aim: To demonstrate the potential of fourth-order polynomials within a non-linear optimization framework for matching-adjusted indirect comparison (MAIC). Materials & methods: Simulated individual patient data were reweighted via fourth-order polynomials (polyMAIC) to match aggregate-level data across multiple baseline characteristics. The polyMAIC approach employed pre-specified matching tolerances and maximum allowable weights. Matching performance against aggregate-level targets was assessed, and also compared against the current industry-standard MAIC approach (Signorovitch). Results: The polyMAIC method matched aggregate-level targets within pre-specified tolerances. Effective sample sizes were either similar to or somewhat higher than those obtained from the Signorovitch method. Performance gains from polyMAIC tended to increase as matching complexity increased. Conclusion: PolyMAIC incorporates greater flexibility than the industry-standard MAIC approach and demonstrates matching potential.

Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS.

BACKGROUND: Debate continues concerning the relevance of neutralizing antibody (NAb) development on the efficacy of interferon (IFN) therapy in patients with multiple sclerosis (MS). The PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study of subcutaneous IFNbeta-1a showed significant benefit on all efficacy outcomes with no significant impact from NAb development on relapses at 2 years. The 2-year extension permitted longer observation following NAb development. METHODS: Exploratory post-hoc analyses of pharmacodynamic response and clinical and MRI outcomes were performed on data from 368 patients with relapsing MS treated with IFN from study start, based on NAb status. RESULTS: Persistent NAbs, above 20 NU/mL, were present in 14% of the 44-microg three times weekly (TIW) and 24% of the 22-microg TIW group over 4 years. NAb development was associated with reduced pharmacodynamic marker induction at 1 year. Over the entire 4 years of study, relapse and disability measures were similar between NAb+ and NAb- patients. However, once NAbs developed, significant differences were noted between NAb+ and NAb- groups, particularly on MRI and relapse measures. The presence of binding antibodies alone did not affect outcome. CONCLUSION: Neutralizing antibody development in interferon-treated patients is correlated with reduced efficacy and is a potential cause for renewed disease activity.