title: Immune parameters of patients treated with laquinimod, a novel oral therapy for the treatment of multiple sclerosis: results from a double-blind placebo-controlled study.
abstract: Laquinimod is a novel orally administered drug for the treatment of relapsing remitting multiple sclerosis (RRMS). In this immunological substudy of the phase III Assessment of Oral Laquinimod in Preventing Progression of MS (ALLEGRO) trial, we performed an ex vivo and in vitro analysis of effects exerted by laquinimod on peripheral blood immune cell populations from RRMS patients with a special focus on monocyte phenotype and function. Approximately 100 patients were enrolled following a standardized protocol. Half of the patients received laquinimod and the other half received placebo. Peripheral blood samples were collected prior to commencement of therapy and after 1, 3, 6, 12, and 24 months of continuous therapy. Main lymphocytic and antigen presenting cell fractions were analyzed in peripheral blood mononuclear cells (PBMCs) ex vivo by flow cytometry. The proliferative response of PBMCs to mitogen or recall antigen was assessed in culture experiments. Untouched monocytes were sorted magnetically and cultured under pro-inflammatory conditions. PBMC analysis showed no significant differences of investigated lymphocytic and antigen presenting cell populations over time within each group, or between the two groups. However, the detailed in vitro analysis of monocytes demonstrated a lower level of CD86 expression on monocytes stimulated with LPS in laquinimod patients beginning from the 1st month of treatment. Upon pro-inflammatory stimulation, monocytes obtained from laquinimod treated patients tended to secrete lower levels of the proinflammatory chemokines CCL2 or CCL5. Taken together, in this prospective study, we demonstrate immune modulation but no immunosuppressive biological activity of laquinimod in a large group of MS patients.
authors.affiliation: Department of Neurology, Polish Mother's Memorial Hospital-Research Institute Lodz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Stasiolek
authors.affiliation: Department of Neurology, Ruhr-University Bochum St. Josef-Hospital, Bochum, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Teva Innovative Research and Development Group, Teva Pharmaceutical Industries Ltd 5 Bazel Street, Petah, Tiqva, 49131, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Hayardeny
authors.affiliation: Teva Innovative Research and Development Group, Teva Pharmaceutical Industries Ltd 5 Bazel Street, Petah, Tiqva, 49131, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Bar Ilan
authors.affiliation: Department of Neurology, Ruhr-University Bochum St. Josef-Hospital, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
keywords: immunomodulation; laquinimod; monocytes; multiple sclerosis; neuroimmunology