Pirfenidone for chronic progressive multiple sclerosis

Current treatment of secondary progressive multiple sclerosis is unsatisfac tory in stabilizing or reversing the disabilities associated with the disea se. Pirfenidone is a new non-peptide drug which has been shown in vitro and in vivo to decrease synthesis of Tumor Necrosis Factor-alpha (TNF-alpha) a nd block receptors for TNF-alpha. Since TNF-alpha seems to be a key cytokin e in demyelination, a pilot study of oral pirfenidone was undertaken in an open-label baseline vs treatment protocol over a 2-year period in 20 patien ts, Fourteen (14/20) patients (70%) remained in the study for 2 years. Thre e (3/20) patients dropped out early because of gastrointestinal adverse rea ctions, and another three patients dropped out for personal reasons after 1 year (not because of adverse reactions). The remaining patients did not ma nifest any other drug-related adverse reactions and complications. Improvem ent or stabilization occurred in most patients at about 3 months, and it wa s sustained at 6, 12 and 24 months as evaluated by both primary and seconda ry outcome measures. Magnetic resonance imaging failed to reveal any new le sions. Thus, pirfenidone appears to offer protection against the usual slow progression of the disease. Most patients experienced a distinct decrease in their neurological disability These findings indicate that an extensive multi-center double blind and placebo controlled trial is warranted.