Efficacy of thalidomide for the treatment of amyotrophic lateralsclerosis: A phase II open label clinical trial

摘要

Neuroinflammation through the cytokine, tumor necrosis factor-alpha (TNF-α) is thought to play an important role in thepathogenesis of amyotrophic lateral sclerosis (ALS). We conducted a preliminary phase II trial of thalidomide, whichreduces levels of TNF-α pre-transcriptionally and post-transcriptionally in vivo and has been shown to prolong diseaseduration and extend the lifespan of transgenic animal models of ALS. Patients who met diagnostic criteria for ALS receivedthalidomide at escalating doses to a target dose of 400 mg/day. The primary endpoints in the trial were the ALS FunctionalRating Scale (ALSFRS) and pulmonary function testing (PFT) curves after nine months of thalidomide treatment that werecompared to historical controls. Secondary endpoints were: survival stratified for newly diagnosed and progressive disease,toxicity, quality of life, and serum cytokine measurements. Twenty-three patients were enrolled, but only 18 were evaluablefor the primary outcome. There was no improvement in the ALSFRS or PFT compared to historical controls. Thalidomidehad several side-effects in our ALS patients. There was no significant shift in cytokine profile after treatment compared tobaseline. In conclusion, treatment of ALS with the TNF-α inhibitor, thalidomide, does not appear to effectively modulatedisease progression and can cause adverse effects.