Evidence Table 14Effectiveness and adverse events in active-control and placebo-controlled trials of mitoxantrone

StudyDosage, PopulationWithdrawalsOutcomesAdverse eventsComments
Bastianello
1994
Italy

Efficacy quality: Fair
AE quality: Fair
MITO
IV 8 mg/m2, 30 min infusion every month, for 1 year

N=13

Male: 5 (38%)
Female: 8 (62%)

Mean age (SD): 30 (5.2)
Total WDs: 0
AE WDs: 0
Mean change in EDSS: −0.27 at 1 year, P=0.18; 95% CI, NR

Proportion of patients with EDSS deterioration: 8% at 1 year, P=0.49; 95% CI, NR

Mean relapse rate: 0.54 at 1 year, P=0.014; 95% CI, NR

Total number of patients experiencing an exacerbation: 5 at 1 year, P=0.02; 95% CI, NR
Amenorrhea: 1/13 (7.7%)

Diarrhea, vomiting and slight fever: 1/13 (7.7%)

Nausea: 7/13 (53.8%)

AEs not separated by drug; AEs of 25 people all together are reported.
On intervention: Mean BL values, MITO vs placebo:
EDSS: 3.7 vs 3.5
Relapses 2 years prior to
study entry: 2.8 vs 3.3
Bastianello
1994
Italy

Efficacy quality: Fair
AE quality: Fair
Placebo

N=12

Male: 5 (42%)
Female: 7 (58%)

Mean age (SD): 28 (6.5)
Total WDs: 0
AE WDs: 0
Mean change in EDSS: 0.08 at 1 year, P=0.18; 95% CI, NR

Proportion of patients with EDSS deterioration: 17% at 1 year, P=0.49; 95% CI, NR

Mean relapse rate: 1.67 at 1 year, P=0.014; 95% CI, NR

Total number of patients experiencing an exacerbation: 10 at 1 year, P=0.02; 95% CI, NR
AEs not separated by treatment arm. AEs of 25 people all together are reported. (See AEs under treatment arm)
Millefiorini
1996
Italy

Efficacy quality: Good
AE quality: Good
MITO
IV 8 mg/m2, once per month, for 1 year

N=27

Male: 10 (37%)
Female: 17 (63%)

Mean age (SD): 31 (6.0)
Total WDs: 4 (15%)
AE WDs: NR
Mean exacerbations per person-year: 0.44 at 2 years, P=0.0002; 95% CI, 0.62 to 2.84

Proportion of patients with EDSS deterioration: 7% at 2 years, P=0.02; 95% CI, 8 to 52

Proportion of relapse-free patients: 63% at 2 years, P=0.006; 95% CI, 15 to 65
Amenorrhea: 5/51 (9.8%)

Headache: 3/51 (5.9%)

Nausea/vomiting: 9/51 (17.6%)

Respiratory infections: 2/51 (3.9%)

UTI: 3/51 (5.9%)

(Data not separated by treatment arms)
On intervention: Mean BL values, MITO vs placebo:
EDSS: 3.6 vs 3.5
Relapses 2 years prior to study entry: 2.8 vs 2.8
Disease duration (years): 5.7 vs 5
Incomplete recruitment generated an imbalance in terms of sex.
Millefiorini
1996
Italy

Efficacy quality: Good
AE quality: Good
Placebo
IV saline solution, once per month, for 1 year

N=27

Male: 10 (37%)
Female: 17 (63%)

Mean age (SD): 31 (6.0)
Total WDs: 5 (21%)
AE WDs: NR
Mean exacerbations per person-year: 1.31 at 2 years, P=0.0002; 95% CI, 0.62 to 2.84

Proportion of patients with EDSS deterioration: 37% at 2 years, P=0.02; 95% CI, 8 to 52

Proportion of relapse-free patients: 21% at 2 years, P=0.006; 95% CI, 15 to 65
Data not separated by treatment arms. See AEs under treatment arm.
Zipoli
2008
MITO vs CPA as second-line therapy

RRMS (active) or SPMS
NRMITO vs CPA
Median time to first relapse: 2.6 years vs 2.5 years, NSD
Time to progression on EDSS: 3.8 yrs vs 3.6 yrs, P=0.04
SPMS and shorter duration of SPMS were significantly associated with higher probability of progression; ARR: MITO 76% reduction (1.7 +/− 1.8 to 0.4 +/− 0.8, P=0.001)
NR

Discontinued therapy: MITO 4 (5%); CPA 17 (22%), P=0.03
Discontinued due to nausea: MITO 20 (27%) vs 28 (36%)

From: Evidence Tables

Cover of Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis
Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet].
Smith B, Carson S, Fu R, et al.
Portland (OR): Oregon Health & Science University; 2010 Aug.
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.

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