In patients with multiple sclerosis treated with fingolimod, there is a risk of disease relapse following cessation of this treatment. |
This study investigated the risk factors associated with an increased disease relapse. |
Disease reactivation following fingolimod cessation is more common in younger patients, those with greater disease activity prior to cessation and those who switch to a low-efficacy therapy. |
1 Introduction
2 Methods
2.1 Participants
2.2 Clinicodemographic Variables
2.3 Statistical Analyses
3 Results
3.1 Sample Characteristics
Variable | Total sample (n =685) | No relapse in 12 months following cessation (n = 467) | Any relapse in 12 months following cessation (n = 218) |
---|---|---|---|
Clinicodemographic | |||
Age at fingolimod cessation (years) | 39.56 (9.88) | 40.75 (10.05) | 37.02 (9.01) |
Female, n (%) | 539 (79) | 356 (76) | 183 (84) |
Disease duration at cessation (years) | 12.31 (7.23) | 12.61 (7.19) | 11.67 (7.30) |
Treatment duration at cessation (years) | 2.51 (1.32) | 2.52 (1.32) | 2.49 (1.34) |
No. of relapses year prior to cessation | 0.54 (0.42) | 0.45 (0.70) | 0.60 (0.77) |
Last EDSS prior to cessation | 3.05 (2.50) | 3.17 (2.11) | 2.81 (1.82) |
Pregnancy within 12 months, n (%) | 72 (11) | 47 (10) | 25 (12) |
New therapy within 12 months, n (%) | |||
None | 92 (13) | 70 (15) | 22 (10) |
Low efficacy | 184 (27) | 117 (25) | 67 (31) |
High efficacy | 409 (60) | 280 (60) | 129 (59) |
Delay to new therapy (months), n (%) | |||
0–2 | 322 (47) | 240 (51) | 82 (38) |
2–4 | 108 (16) | 60 (13) | 48 (22) |
4–6 | 48 (7) | 25 (5) | 23 (11) |
6–8 | 25 (4) | 13 (3) | 12 (6) |
8–10 | 19 (3) | 12 (3) | 7 (3) |
10–12 | 22 (3) | 11 (2) | 11 (5) |
> 12 | 141 (21) | 106 (23) | 35 (16) |
3.2 Relapse Rates
ARR [95% CI] | |||
---|---|---|---|
Cohort | Before treatment | During treatment | After cessation |
All (n = 685) | 1.71 [1.59, 1.85] | 0.50 [0.44, 0.55] | 0.43 [0.38, 0.49] |
Switch to new therapy (12 months) | |||
None (n = 92) | 1.38 [1.09, 1.73] | 0.28 [0.17, 0.42] | 0.26 [0.16, 0.36] |
Low efficacy (n = 184) | 1.38 [1.17, 1.60] | 0.33 [0.24, 0.41] | 0.51 [0.40, 0.62] |
High efficacy (n = 409) | 1.95 [1.79, 2.13] | 0.62 [0.54, 0.69] | 0.44 [0.36, 0.51] |
Time to switch (months) | |||
0–2 (n = 322) | 1.87 [1.68, 2.07] | 0.58 [0.50, 0.67] | 0.38 [0.27, 0.42] |
2–4 (n = 108) | 1.72 [1.43, 2.03] | 0.52 [0.39, 0.67] | 0.53 [0.41, 0.65] |
4–6 (n = 48) | 1.21 [0.81, 1.68] | 0.29 [0.13, 0.48] | 0.71 [0.46, 0.98] |
6–8 (n = 25) | 1.72 [0.96, 2.64] | 0.44 [0.16, 0.84] | 0.80 [0.44, 1.37] |
8–10 (n = 19) | 1.74 [1.11, 2.32] | 0.32 [0.11, 0.58] | 0.84 [0.32, 1.68] |
10–12 (n = 22) | 1.23 [0.64, 2.18] | 0.23 [0.05, 0.36] | 0.86 [0.45, 1.41] |
12+ (n = 141) | 1.60 [1.35, 1.88] | 0.42 [0.31, 0.54] | 0.28 [0.20, 0.38] |
3.3 Predictors of Relapse
3.4 Severe Relapses
ARR [95%] | |||
---|---|---|---|
Cohort | Before treatment | During treatment | After cessation |
All (n = 685) | 0.05 [0.03, 0.07] | 0.02 [0.01, 0.03] | 0.02 [0.01, 0.04] |
Switch to new therapy (12 months) | |||
None (n = 92) | 0.05 [0.01, 0.12] | 0.01 [0.00, 0.03] | – |
Low efficacy (n = 184) | 0.04 [0.02, 0.08] | 0.01 [0.00, 0.02] | 0.04 [0.02, 0.08] |
High efficacy (n = 409) | 0.05 [0.03, 0.08] | 0.03 [0.01, 0.04] | 0.02 [0.01, 0.04] |
Time to switch (months) | |||
0–2 (n = 322) | 0.04 [0.02, 0.07] | 0.02 [0.01, 0.03] | 0.03 [0.01, 0.04] |
2–4 (n = 108) | 0.07 [0.02, 0.16] | 0.04 [0.01, 0.07] | 0.04 [0.00, 0.09] |
4–6 (n = 48) | 0.02 [0.00, 0.06] | 0.02 [0.00, 0.06] | 0.02 [0.00, 0.06] |
6–8 (n = 25) | – | – | 0.08 [0.00, 0.02] |
8–10 (n = 19) | 0.11 [0.00, 0.21] | 0.05 [0.00, 0.16] | 0.05 [00.0, 0.16] |
10–12 (n = 22) | 0.14 [0.00, 0.41] | 0 | 0.05 [0.00, 0.14] |
12+ (n = 141) | 0.05 [0.01, 0.09] | 0.01 [0.00, 0.02] | – |
3.5 Freedom from Relapses After Discontinuing Fingolimod
Term | Exp(B) [95% CI] | |
---|---|---|
Number of relapses | First relapse | |
Clinicodemographic | ||
Sex (male) | 0.62 [0.43, 0.87] | 0.89 [0.67, 1.18] |
Age at cessation | 0.96 [0.94, 0.98] | 0.97 [0.95, 0.98] |
Disease duration at cessation | 1.01 [0.99, 1.03] | 1.01 [0.99, 1.03] |
Treatment duration | 1.02 [0.93, 1.12] | 1.02 [0.93, 1.12] |
ARR year before cessation | 1.29 [1.10, 1.51] | 1.36 [1.18, 1.56] |
EDSS before cessation | 1.02 [0.95, 1.09] | 1.00 [0.94, 1.07] |
Pregnancy post-fingolimod | 1.35 [0.90, 1.99] | 0.88 [0.58, 1.33] |
Switch to new therapy (12 months)a | ||
Switched to no treatment | 0.89 [0.45, 1.80] | 1.49 [0.84, 2.65] |
Switched to low efficacy | 1.47 [1.12, 1.94] | 1.52 [1.17, 1.98] |
Time to switchb (months) | ||
2–4 | 1.63 [1.16, 2.27] | 1.67 [1.22, 2.27] |
4–6 | 2.31 [1.51, 3.46] | 2.08 [1.38, 3.14] |
6–8 | 2.29 [1.34, 3.74] | 1.56 [0.88, 2.76] |
8–10 | 2.07 [1.13, 3.57] | 1.45 [0.75, 2.76] |
10–12 | 1.96 [1.10, 3.33] | 1.71 [0.93, 3.15] |
12+ | 0.79 [0.44, 1.32] | 0.83 [0.50, 1.37] |
Time interval (months) | No. of relapses | ARR [95% CI] | ||
---|---|---|---|---|
On treatment | Not on treatment | On treatment | Not on treatment | |
0–2 | 19 | 34 | 0.72 [0.25, 1.19] | 0.39 [0.20, 0.57] |
2–4 | 32 | 41 | 0.49 [0.24, 0.76] | 0.81 [0.45, 1.18] |
4–6 | 23 | 23 | 0.30 [0.12, 0.48] | 0.60 [0.26, 0.95] |
6–8 | 27 | 14 | 0.33 [0.15, 0.51] | 0.43 [0.11, 0.76] |
8–10 | 29 | 14 | 0.34 [0.16, 0.52] | 0.49 [0.13, 0.83] |
10–12 | 31 | 8 | 0.35 [0.17, 0.52] | 0.32 [0.01, 0.62] |