Long-term treatment of multiple sclerosis with glatiramer acetate: Natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy

A retrospective phase IV study was designed to evaluate the anti-GA antibody subtypes, test their in vitro neutralizing activity and correlate these parameters with the clinical efficacy, in long-term GA treatment of MS patients. Serum samples from 153 MS patients, 126 treated with GA for 2 to 15 years (mean 6.6 years) and 27 treated for < 2 years, were collected. Anti-myelin basic protein (MBP) and anti-GA antibodies were measured by specific ELISA. Neutralizing activity was determined by the capacity of the serum to inhibit the proliferation of GA-specific T-cells. Anti-GA antibodies were detected even after very long treatment periods, although at lower levels. Anti-MBP reactivity remained consistently negative. The IgG2 isotype of anti-GA antibodies and the multiple sclerosis severity scale (MSSS) was lower in the long-term treated patients P = 0.0003 and 0.016 respectively. The neutralizing activity of anti-GA antibodies was insignificant. Our results indicate that the clinical efficacy of GA treatment could be associated with a decrease in anti-GA IgG2 isotype in long-term GA-treated patients.