Goodin
et al. Cause of death in MS:
long-term follow-up of a randomised cohort, 21 years after the start of
the pivotal IFNβ-1b study. BMJ Open. 2012 Nov 30;2(6). doi:pii: e001972. 10.1136/bmjopen-2012-001972. Print 2012.
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.
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.
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.
"The bottom line is that starting
treatment with interferon beta 3-years earlier, compared to MSers in
the placebo-arm, increased their chance of being alive at 21 years by
~50%. In addition, the number of relapses in the 2-years on the trial
also predicted mortality; another reason to reduce relapses early on in
the course of MS and necessarily within the first 2-years."