The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART'MUS) trial: rationale, objectives and state of advancement.

Multiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system, which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss. It usually begins with acute episodes of neurological dysfunction, the relapses, followed by periods of partial or complete remission. This relapsing-remitting phase is usually followed by a steady, continuous and irreversible worsening of the neurological dysfunction, which characterizes the progressive phase of the disease. Recent prospective studies reported a significant decline by two-third in the rate of relapses during the third trimester of pregnancy and a significant increase by two-third during the first three months post-partum by comparison to the relapse rate observed during the year prior to the pregnancy. These dramatic changes in the relapse rate occur at a time when impregnation of many substances, among which sexual steroids, is at its highest, before a dramatic decline to the pre-pregnancy levels, immediately following delivery. It may be hypothesized that sexual steroids could exert beneficial effects through a modulation of the immune state with a lowering of the pro-inflammatory lymphocyte responses of the Th1 type and an enhancement of anti-inflammatory responses of the Th2 type. They may also play a direct role in remyelination of central nervous system lesions, as they do in the peripheral nervous system, where progesterone increases the extent of myelin sheath formation after a cryolesion of the male mouse sciatic nerve. The POPART'MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administrating high doses of progestin, in combination with endometrial protective doses of estradiol. Treatment is given immediately after delivery and continuously during the first three months post-partum. At present, 126 patients have been enrolled and 107 patients have completed the protocol. Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum. The trial is registered under the reference NTC00127075.

RCT Entities:   Population Interventions Outcomes