PT  - JOURNAL ARTICLE
AU  - Mike Ufer
AU  - Kasra Shakeri-Nejad
AU  - Anne Gardin
AU  - Zhenzhong Su
AU  - Ines Paule
AU  - Thomas C. Marbury
AU  - Eric Legangneux
TI  - Impact of siponimod on vaccination response in a randomized, placebo-controlled study
AID  - 10.1212/NXI.0000000000000398
DP  - 2017 Nov 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e398
VI  - 4
IP  - 6
4099  - http://nn.neurology.org/content/4/6/e398.short
4100  - http://nn.neurology.org/content/4/6/e398.full
SO  - Neurol Neuroimmunol Neuroinflamm2017 Nov 01; 4
AB  - Objective: To evaluate effects of siponimod on response to T-cell–dependent (influenza) and T-cell–independent (pneumococcal polysaccharide vaccine [PPV-23]) vaccinations in healthy participants.Methods: In this double-blind, placebo-controlled, parallel-group study, each participant underwent a 7-week treatment period and received intramuscular injections of influenza and PPV-23 vaccines (day 21). Participants were randomized to 4 treatment groups (N = 30 each) and received placebo or siponimod 2 mg once daily in concomitant, interrupted, or preceding fashion. Individual response to vaccination was defined by a ≥4-fold (influenza) antibody titer increase and by a ≥2-fold increase in serotype-specific immunoglobulin (Ig) G concentrations (PPV-23) on day 28 vs baseline. Responder rates were compared using noninferiority analysis.Results: Mean influenza titers were similar to placebo in the preceding and interrupted groups but lower in the concomitant group. The proportion of participants with influenza titers ≥40 four weeks after vaccination (seroprotection) was similar to placebo across all groups and antigens. In each treatment group, response criteria were met for 3 of 4 antigens including H1N1 and H3N2. A noninferior response was determined in the context of preceding treatment but not interrupted or concomitant treatment. Regarding PPV-23, approximately 90%–100% of participants exhibited a ≥2-fold increase in IgG concentrations vs baseline. Noninferior responder rates were determined for each siponimod treatment group.Conclusions: Siponimod treatment had no relevant effect on antibody response to PPV-23. European Medicines Agency response criteria were essentially met for influenza, but titers were lower on concomitant treatment. Overall, these data suggest that siponimod has limited effect on the efficacy of vaccinations with neoantigens.Classification of evidence: This study provides Class II evidence that in healthy persons, siponimod had limited effect on the immune response following influenza or pneumococcal vaccinations.AE=adverse event; CI=confidence interval; EMA=European Medicines Agency; GMT=geometric mean titer; HIA=hemagglutination inhibition assay; Ig=immunoglobulin; LC-MS=liquid chromatography–mass spectrometry; MS=multiple sclerosis; PD=pharmacodynamic; PK=pharmacokinetic; PPV-23=pneumococcal polysaccharide vaccine; q.d.=once daily; S1P=sphingosine 1-phosphate