This study investigated if this pharmacodynamic effect impacts humoral (antibodies and B cells) and cellular (T cell) immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo.
The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH. Limpet blood protien), and pneumococcal (pneumonia bacteria) polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus (lockjaw) toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans (Thrust, yeast).
Fingolimod caused mild to moderate decreases in antibody response to anti-KLH and anti-PPV-23 IgG and IgM antibody levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both greater than 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.
The study indicated that there was a modest reduction in antibody responses, which would equate to some reduced capacity to deal with infections but T cell responses as tested using DTH skin swelling response to infections to which we have immunity was unaffected. This is good because it means Gilenya is not completely removing our protective immunity, however we should expect some infection issues as there were some in clinical trials.