Pentoxifylline in ALS: a double-blind, randomized, multicenter, placebo-controlled trial.
OBJECTIVE
To assess the efficacy and safety of pentoxifylline, a US Food and Drug Administration-approved drug, in patients with ALS treated with riluzole.


METHODS
The authors conducted a double-blind, randomized, placebo-controlled, multicenter trial. Four hundred patients with probable or definite ALS and vital capacity less than 100% were randomly assigned to treatment with placebo or 1.2 g pentoxifylline daily. The primary outcome was death. Secondary outcomes were rates of deterioration of ALS Functional Rating Scale-Respiratory and muscle strength. The primary intention-to-treat analysis was the survival comparison of drug vs placebo, assessed before (log-rank test) and after adjustment (Cox model) for predefined prognostic factors.


RESULTS
At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In contrast, analysis of secondary outcome functional variables did not show the same negative effect of the drug. The most common adverse reactions were nausea, dysphagia, and flushing, all reversible after stopping the drug.


CONCLUSIONS
Pentoxifylline is not beneficial in ALS and should be avoided in patients treated with riluzole. The discrepancy between survival and measures of functional changes urges caution in equating these end points in phase III trials, and suggests that both survival and function should be used in phase III trials.
Meininger
V
V
Fédération des Maladies du Système Nerveux, Pavillon Paul Castaigne, AP-HP, Hôpital de la Salpétrière, Paris, France. vincent.meininger@psl.aphp.fr
Asselain
B
B
Guillet
P
P
Leigh
P N
PN
Ludolph
A
A
Lacomblez
L
L
Robberecht
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000009:adverse effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010919:Placebos; D019782:Riluzole / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D019782:Riluzole; D010431:Pentoxifylline