GLPG0259 + methotrexate

GLPG0259 + methotrexate is a combination therapy investigated for the treatment of rheumatoid arthritis. GLPG0259 is a small molecule inhibitor of mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5), a kinase implicated in inflammatory signaling. Methotrexate is an established disease-modifying antirheumatic drug (DMARD) and the standard of care for rheumatoid arthritis. The combination was explored in clinical studies based on the hypothesis that dual mechanism inhibition (novel pathway inhibition by GLPG0259 and established anti-inflammatory action of methotrexate) could yield superior efficacy in methotrexate-refractory patients. The development program included Phase I studies showing safety and tolerability of the combination, but a Phase II trial found no added efficacy over placebo/methotrexate and development was terminated for this indication[1][2][3][4][5][7].