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CNS Drugs

, Volume 33, Issue 1, pp 93–97 | Cite as

Correction to: Oral Disease-Modifying Treatments for Relapsing Multiple Sclerosis: A Likelihood to Achieve No Evidence of Disease Activity or Harm Analysis

  • Dimitrios Papadopoulos
  • Dimos-Dimitrios D. MitsikostasEmail author
Correction
  • 190 Downloads

1 Correction to: CNS Drugs (2018) 32:1069–1078  https://doi.org/10.1007/s40263-018-0547-z

Page 1069, Abstract, Results—the text that read:

The values for likelihood to achieve NEDA than experience any AE ratio (LHH(AE/NEDA)) were 3.9, 6.8, 12.5 and 3.7, the likelihood to achieve NEDA than experience a SAE ratio (LHH(SAE/NEDA)) values were 3.5, 15, 23.5 and 2.8, and the likelihood to achieve NEDA versus discontinue treatment (LHH(AE-D/NEDA)) values were 20.3, 4.3, 3.9 and 3.1 for cladribine, dimethyl-fumarate, fingolimod, and teriflunomide, respectively.

Should read:

The values for likelihood to achieve NEDA than experience any AE ratio (LHH(AE/NEDA)) were 3.5, 6.8, 12.5 and 2.6, the likelihood to achieve NEDA than experience a SAE ratio (LHH(SAE/NEDA)) values were 13.0, 3.5, 23.5 and 2.7, and the likelihood to achieve NEDA versus discontinue treatment (LHH(AE-D/NEDA)) values were 17.7, 6.5, 4.6 and 3.0 for cladribine, dimethyl-fumarate, fingolimod, and teriflunomide, respectively.

Page 1073, column 1, lines 9 to 12—the text that read:

NEDA was evaluated as the proportion of patients free of relapses, 3-month confirmed disability progression, and free of new or newly enlarging T2 lesion and Gadolinium enhancing lesions.

Should read:

NEDA was evaluated as the proportion of patients free of relapses and 3-month confirmed disability progression, and free of new and newly enlarging T2 lesion and Gadolinium-enhancing lesions.

Page 1073, column 2, section 3.2, line 2—the text that read:

… eight (95% CI 5.3–11.5) for DMF …

Should read:

… eight (95% CI 5.0–11.9) for DMF …

Page 1074, column 1, section 3.3, lines 7 to 12—the text that read:

The NNTHAE values were 15 (95% CI 7.8 to 65.2) for cladribine, 52 (95% CI 23.6 to − 270.1) for DMF, 68 (95% CI 27.7 to − 153.1) for fingolimod, and 44 (95% CI 14.6 to − 44.2) for teriflunomide, indicating that fingolimod has the most and cladribine the least favorable safety profile with regard to the appearance of any AE (Table 4).

Should read:

The NNTHAE values were 14 (95% CI 7.7 to 56.2) for cladribine, 52 (95% CI 23.6 to − 270.1) for DMF, 68 (95% CI 27.7 to − 153.1) for fingolimod, and 31 (95% CI 12.8 to − 79.2) for teriflunomide, indicating that fingolimod has the most and cladribine the least favorable safety profile with regard to the appearance of any AE (Table 4).

Page 1074, column 1, section 3.3, lines 15 to 19—the text that read:

Nevertheless, with regard to the AEs that led to treatment discontinuation, the NNTHAE-D was most favorable for cladribine (72 (95% CI 27.9 to − 129.5]) and least favorable for fingolimod (21 [95% CI 12.6 to 54.1]) (Table 4).

Should read:

Nevertheless, with regard to the AEs that led to treatment discontinuation, the NNTHAE-D was most favorable for cladribine (71 (95% CI 27.9 to − 129.5]) and least favorable for fingolimod (28 [95% CI 15.0 to 191.6]) (Table 4).

Page 1074, column 2, section 3.4, lines 8 to 12—the text that read:

Nevertheless, calculating the likelihood to achieve NEDA versus discontinue treatment due to an AE cladribine has the most favourable efficacy versus risk profile (LHH(AE-D/NEDA) 20.3 [95% CI 7.03–37.48]).

Should read:

Nevertheless, calculating the likelihood to achieve NEDA versus discontinue treatment due to an AE cladribine has the most favourable efficacy versus risk profile (LHH(AE-D/NEDA) 17.7 [95% CI 7.03–37.48]).

Table 2 that read:

Table 2

Source data

Treatment arm

Cladribine

Dimethyl-fumarate

Fingolimod

Teriflunomide

Active

Placebo

Active

Placebo

Active

Placebo

Active

Placebo

Patients that achieved NEDA

 Proportion (n)

178/402

60/379

132/511a

43/356a

213/783

65/773

82/358

52/363

 Percentage (%)

44.3

15.8

26

12

27.2

8.4

22.9

14.3

Patients in safety analysis (n)

433

437

769

771

783

773

360

358

Proportion of patients with any  AE (n)

347/433

319/437

733/769

720/771

751/783

730/773

325/360

315/358

Proportion of patients with any SAE (n)

36/433

28/437

135/769

165/771

96/783

101/773

57/360

46/358

Proportion of patients that discontinued treatment due to an AE (n)

15/433

9/437

109/769

93/771

101/783

62/773

39/360

29/358

References

[11, 21]

 

[12, 13, 18, 19]

 

[14, 15, 20]

 

[16, 22]

 

AE adverse event, MRI magnetic resonance imaging, NEDA no evidence of disease activity, SAE serious adverse event

aDimethyl-fumarate and placebo patients used for the NEDA analysis (MRI cohort) were the subpopulation of patients from DEFINE and CONFIRM with MRI data

Should read:

Table 2

Source data

Treatment arm

Cladribine

Dimethyl-fumarate

Fingolimod

Teriflunomide

Active

Placebo

Active

Placebo

Active

Placebo

Active

Placebo

Patients that achieved NEDA

 Proportion (n)

178/402

60/379

90/345a

41/347a

213/783

65/773

82/358

52/363

 Percentage (%)

44.3

15.8

26.1

11.8

27.2

8.4

22.9

14.3

Patients in safety analysis (n)

430

435

769

771

783

773

358

360

Proportion of patients with any  AE (n)

347/430

319/435

733/769

720/771

751/783

730/773

325/358

315/360

Proportion of patients with any SAE (n)

36/430

28/435

135/769

165/771

96/783

101/773

57/358

46/360

Proportion of patients that discontinued treatment due to an AE (n)

15/430

9/435

109/769

93/771

98/783

69/773

39/358

29/360

References

[11, 21]

 

[12, 13, 18, 19]

 

[14, 15, 20]

 

[16, 22]

 

AE adverse event, MRI magnetic resonance imaging, NEDA no evidence of disease activity, SAE serious adverse event

aDimethyl-fumarate and placebo patients used for the NEDA analysis (MRI cohort) were the subpopulation of patients from DEFINE and CONFIRM with MRI data

Table 3 that read:

Table 3

Numbers needed to treat for one patient to achieve no evidence of disease activity (NNTBNEDA)

 

Cladribine (CLARITY)

Dimethyl-fumarate (pooled DEFINE + CONFIRM)

Fingolimod (pooled FREEDOMS + FREEDOMS II)

Teriflunomide (TEMS0)

Total (n)

812

867

1561

721

RR

2.79

2.13

3.23

1.59

95% CI

2.16–3.61

1.55–2.93

2.5–4.2

1.16–2.19

p value

< 0.0001

< 0.0001

< 0.0001

< 0.0035

AR

0.28

0.13

0.19

0.08

NNTBNEDA

4

8

6

12

95% CI

2.9–4.5

5.3–11.9

4.4–6.6

7.0–34.1

AR attributable risk (proportion of patients achieving NEDA in active group minus proportion of patients achieving NEDA in placebo group), CI confidence interval, NEDA no evidence of disease activity, NNTBNEDA number of patients needed to treat for a patient to achieve NEDA, RR relative risk (proportion of patients achieving NEDA in active group out of the total patients in the active group over the proportion of patients achieving NEDA in placebo group out of the total patients in placebo group)

Should read:

Table 3

Numbers needed to treat for one patient to achieve no evidence of disease activity (NNTBNEDA)

 

Cladribine (CLARITY)

Dimethyl-fumarate (pooled DEFINE + CONFIRM)

Fingolimod (pooled FREEDOMS + FREEDOMS II)

Teriflunomide (TEMS0)

Total (n)

781

692

1556

721

RR

2.79

2.13

3.23

1.59

95% CI

2.16–3.61

1.55–2.93

2.5–4.2

1.16–2.19

p value

< 0.0001

< 0.0001

< 0.0001

< 0.0035

AR

0.28

0.13

0.19

0.08

NNTBNEDA

4

8

6

12

95% CI

2.9–4.5

5.0–11.9

4.4–6.6

7.0–34.1

AR attributable risk (proportion of patients achieving NEDA in active group minus proportion of patients achieving NEDA in placebo group), CI confidence interval, NEDA no evidence of disease activity, NNTBNEDA number of patients needed to treat for a patient to achieve NEDA, RR relative risk (proportion of patients achieving NEDA in active group out of the total patients in the active group over the proportion of patients achieving NEDA in placebo group out of the total patients in placebo group)

Table 4 that read:

Table 4

Numbers needed to harm (NNTH) analysis of safety

 

Cladribine

CLARITY

DMF (pooled DEFINE and CONFIRM)

Fingolimod (pooled FREEDOMS and  FREEDOMS II)

Teriflunomide

TEMSO

NNTHAE

15

52

68

44

95% CI

7.8–65.2

NNTH 23.6 to ∞ to

NNTB 270.1a

27.7 to ∞ to

NNTB 153.1

14.6 to ∞ to

NNTB 44.2

NNTHSAE

53

27

125

34

95% CI

18.6 to ∞ to

NNTB 64a

12.8 to ∞ to

NNTB 947.3a

24.3 to ∞ to

NNTB 40a

12/3 to ∞ to

NNTB 46.8a

NNTHAE-D

72

48

21

37

95% CI

27.9 to ∞ to

NNTB 129.5a

18.2 to ∞ to

NNTB 79.4a

12.6–54.1

14/3 to ∞ to

NNTB 64.7a

AE adverse event, AE-D adverse event leading to treatment discontinuation, CI confidence interval, DMF dimethyl-fumarate, NNTB number of patients needed to treat for a patient to have a good outcome (to achieve no evidence of activity), NNTH number of patients needed to treat for a patient to have a harmful outcome, SAE serious adverse event. In some cases the harmful effect of the treatment leading to an AE was not significantly different from placebo at the p 0.05 level and resulted in the 95% CIs of the NNTH to include infinity (∞)

aNo significant difference between active treatment and placebo

Should read:

Table 4

Numbers needed to harm (NNTH) analysis of safety

 

Cladribine

CLARITY

DMF (pooled DEFINE and CONFIRM)

Fingolimod (pooled FREEDOMS and  FREEDOMS II)

Teriflunomide

TEMSO

NNTHAE

14

52

68

31

95% CI

7.7–56.2

NNTH 23.6 to ∞ to

NNTB 270.1a

27.7 to ∞ to

NNTB 153.1

12.8 to ∞ to

NNTB 79.2

NNTHSAE

52

27

125

32

95% CI

18.6 to ∞ to

NNTB 64a

12.8 to ∞ to

NNTB 947.3a

24.3 to ∞ to

NNTB 40a

12.1 to ∞ to

NNTB 50.5a

NNTHAE-D

71

48

28

36

95% CI

27.7 to ∞ to

NNTB 129.7a

18.2 to ∞ to

NNTB 79.4a

15–191.6

14.0 to ∞ to

NNTB 69.4a

AE adverse event, AE-D adverse event leading to treatment discontinuation, CI confidence interval, DMF dimethyl-fumarate, NNTB number of patients needed to treat for a patient to have a good outcome (to achieve no evidence of activity), NNTH number of patients needed to treat for a patient to have a harmful outcome, SAE serious adverse event. In some cases the harmful effect of the treatment leading to an AE was not significantly different from placebo at the p 0.05 level and resulted in the 95% CIs of the NNTH to include infinity (∞)

aNo significant difference between active treatment and placebo

Figure 1 that was:

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Multiple Sclerosis Centre and Neurology SectionAthens Medical Centre - Paleo Phaliro ClinicAthensGreece
  2. 2.1st Neurology Department, Aeginition Hospital, Medical SchoolNational and Kapodistrian University of AthensAthensGreece

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