A double-blind, randomized, controlled study of oral pirfenidone for treatment of secondary progressive multiple sclerosis

Currently, there are no approved treatments for secondary progressive multiple sclerosis (MS) that stabilize or reverse the neurological disabilities associated with this disease. Oral pirfenidone was found to stabilize and overcome the disabilities in two published independent open-label studies in secondary progressive MS. This led us to study pirfenidone in a phase II double-blind, randomized and controlled, clinical trial in patients with advanced secondary progressive MS for 12 months. Forty-three patients met the eligibility criteria approved by the IRB and accepted by the FDA. Of these patients, 18 were randomly assigned to placebo and 25 patients to oral pirfenidone groups. All eligible patients were included in the statistical analysis of the data according to intention-to-treat principles. Some patients on oral pirfenidone manifested mild drug-related adverse effects, but it was well tolerated overall. By one month, pirfenidone significantly (P<0.05) improved the Scripps Neurological Rating Scale (SNRS) scores, and scores remained significantly improved for 3, 6 and 12 months when compared to the baseline SNRS scores. In contrast, the SNRS scores of patients on oral placebo were not significantly improved at 1, 3, 6 or 12 months of the study, when compared with baseline scores. Oral pirfenidone significantly (P<0.04) reduced the incidence of relapses (27.8% on placebo versus 8.0% on pirfenidone). Furthermore, oral pirfenidone treatment was associated with a marked improvement in bladder dysfunction (40.0% on pirfenidone versus 16.7% on placebo). Expanded Disability Status Scale scores and MRI lesion count were not significantly different in the placebo and pirfenidone groups. These findings indicate a significant effect of pirfenidone on clinical disability and bladder function for secondary progressive MS patients. A major multicentre, double-blind, randomized, controlled trial is justified.

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Evaluating the Role of Corticosteroid Pulse Therapy in Patients With Secondary Progressive Multiple Sclerosis Receiving Mitoxantrone: A Double Blind Randomized Controlled Clinical Trial

Iranian Red Crescent Medical Journal ◽

10.5812/ircmj.30618 ◽

2015 ◽

Vol 17 (10) ◽

Cited By ~ 1

Author(s):

Abolghasem Rahimdel ◽

Ahmad Zeinali ◽

Ali Mellat

Keyword(s):

Multiple Sclerosis ◽

Pulse Therapy ◽

Progressive Multiple Sclerosis ◽

Controlled Clinical Trial ◽

Randomized Controlled Clinical Trial ◽

Double Blind ◽

Secondary Progressive ◽

Randomized Controlled ◽

Corticosteroid Pulse Therapy

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Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/135245859800400206 ◽

1998 ◽

Vol 4 (2) ◽

pp. 74-78 ◽

Cited By ~ 14

Author(s):

B Dubois ◽

M B D'Hooghe ◽

K De Lepeleire ◽

P Ketelaer ◽

G Opdenakker ◽

...

Keyword(s):

Multiple Sclerosis ◽

Pilot Trial ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Tissue Type ◽

Control Group ◽

Double Blind ◽

Gelatinase B ◽

Double Blind Placebo ◽

Secondary Progressive

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficaceous protease inhibitors than those used in the combination therapy described here.

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