Citation

Goodin DS, Ebers GC, Cutter G, Cook SD, O'Donnell T, Reder AT, Kremenchutzky M, Oger J, Rametta M, Beckmann K, Knappertz V. BMJ Open 2012; 2(6).

Copyright

(Copyright © 2012, BMJ Publishing Group)

DOI

10.1136/bmjopen-2012-001972

PMID

unavailable

Abstract

OBJECTIVES: Compared with controls, multiple sclerosis (MS) patients die, on average, 7-14 years prematurely. Previously, we reported that, 21 years after their participation in the pivotal randomised, controlled trial (RCT) of interferon β-1b, mortality was reduced by 46-47% in the two groups who received active therapy during the RCT. To determine whether the excessive deaths observed in placebo-treated patients was due to MS-related causes, we analysed the causes-of-death (CODs) in these three, randomised, patient cohorts.

DESIGN: Long-term follow-up (LTF) of the pivotal RCT of interferon β-1b. Setting: Eleven North American MS-centres participated. Participants: In the original RCT, 372 patients participated, of whom 366 (98.4%) were identified after a median of 21.1 years from RCT enrolment. Interventions: Using multiple information sources, we attempted to establish COD and its relationship to MS in deceased patients. Primary outcome: An independent adjudication committee, masked to treatment assignment and using prespecified criteria, determined the likely CODs and their MS relationships.

RESULTS: Among the 366 MS patients included in this LTF study, 81 deaths were recorded. Mean age-at-death was 51.7 (±8.7) years. COD, MS relationship, or both were determined for 88% of deaths (71/81). Patients were assigned to one of nine COD categories: cardiovascular disease/stroke; cancer; pulmonary infections; sepsis; accidents; suicide; death due to MS; other known CODs; and unknown COD. Of the 69 patients for whom information on the relationship of death to MS was available, 78.3% (54/69) were adjudicated to be MS related. Patients randomised to receive placebo during the RCT (compared with patients receiving active treatment) experienced an excessive number of MS-related deaths.

CONCLUSIONS: In this long-term, randomised, cohort study, MS patients receiving placebo during the RCT experienced greater all-cause mortality compared to those on active treatment. The excessive mortality in the original placebo group was largely from MS-related causes, especially, MS-related pulmonary infections.

Language: en

Keywords

adult; human; North America; suicide; injury; randomized controlled trial; cause of death; article; major clinical study; controlled study; lung embolism; placebo; cerebrovascular accident; sepsis; follow up; cardiovascular disease; accidental death; brain dysfunction; infection; respiratory failure; aspiration pneumonia; lung infection; neoplasm; multiple sclerosis; brain stem; idiopathic disease; outcome assessment; interferon beta serine; randomized controlled trial (topic)