Table 3.
Summary of previous studies of natalizumab EID versus SID.
| Publication | Sample sizes | Dosing definitions | Observed average dosing intervals | Prior SID exposure for EID group | Follow-up time | Efficacy outcomes | PML outcomes | Author conclusion |
|---|---|---|---|---|---|---|---|---|
| Zhovtis Ryerson et al.7 | SID: 1080 EID: 894 |
SID defined as Q4W EID defined as ⩾31 days |
SID: 30 days EID: 31–61 days |
⩾6 months Q4W dosing | Q4W: 27.39 doses (mean) EID: 40.07 doses (mean total); 24.96 (mean as EID) |
Proportion with no new MRI activity: 81% during Q4W 82% during EID Proportion with no new clinical activity: 74% during Q4W 75% during EID: Proportion with no new MRI activity and no new clinical activity: 62% during Q4W 78% during EID |
Q4W: 4 cases EID: no cases |
‘Dosing intervals up to 8 weeks and 5 days did not diminish effectiveness of natalizumab therapy’. |
| Yamout et al.8 | SID: 85 EID: 85 (all participants switched to EID) |
SID defined as Q4W EID defined as ⩾35 days |
SID: Not reported EID: 35–56 days |
Mean of 15.4 months Q4W dosing | Q4W: 15.4 months EID: 11.8 months |
Proportion relapse free: At end of Q4W 95.3% At end of EID 93.9% Proportion with no new MRI activity: 81.2% at end of Q4W 92.0% at end of EID Mean (SD) EDSS score: 2.56 (1.62) at end of Q4W 2.59 (1.61) at end of EID |
EID: no cases | ‘In patients treated with natalizumab, shifting from Q4W dosing to EID has no negative effect on efficacy as evidenced by relapse rate, disability progression, and MRI activity’. |
| Bomprezzi and Pawate10 | SID: 361 EID: 96 |
SID defined as Q4W EID defined as 42–56 days |
SID: not reported EID: not reported |
Mean of 22 months Q4W dosing (range, 12–24 months) | Q4W: 22 months (mean) EID: ⩾6 months (mean 20 months) |
Proportion relapsed: 13% during Q4W 13% during EID Proportion with new MRI activity: 11% during Q4W 9% during EID |
Not reported | ‘EID did not compromise the treatment effect as measured by relapse rate, and no significant breakthrough disease activity was observed’. |
| Clerico et al.11 | SID: 216 EID: 144 |
SID defined as < 35 days EID defined as ⩾35 days |
SID: 30.1 days during first 6 months of follow-up; 30.8 days overall EID: 43.4 days during first 6 months of follow-up; 42 days overall |
6 months SID | SID and EID: 2.2 years | ARR (95% CI): SID: 0.060 (0.033, 0.087) EID: 0.039 (0.017, 0.063) |
SID: no cases EID: no cases |
‘In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting’. |
| Chisari et al.17 | SID: 1254 EID: 838 |
SID defined as 28–32 days EID defined as 33–49 days |
SID: 30.8 days EID: 39.8 days |
⩾6 months | SID and EID: Follow-up assessments at 12 months and 24 months | Proportion relapsed at 12 months: SID: 4.3% EID: 3.5% Proportion relapsed at 24 months: SID: 3.7% EID: 3.1% Mean (SD) ARR at 12 months: SID: 0.10 (0.09) EID: 0.11 (0.08) Mean (SD) ARR at 24 months: SID: 0.09 (0.05) EID: 0.10 (0.05) Mean (SD) EDSS score at 12 months: SID: 3.1 (2.9) EID: 3.2 (2.5) Mean (SD) EDSS score at 24 months: SID: 3.3 (2.8) EID: 3.4 (2.1) |
Not reported | ‘The use of natalizumab with an extended interval schedule showed similar effectiveness compared with SID’. |
ARR, annualized relapse rate; CI, confidence interval; EDSS, Expanded Disability Status Scale; EID, extended interval dosing; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy; Q4W, every 4 weeks; SD, standard deviation; SID, standard interval dosing.