Abstract
Background: The efficacy of alemtuzumab, a highly effective anti-CD52 agent, was shown to be superior compared with interferon β in relapsing-remitting multiple sclerosis (MS). However, its efficacy relative to other potent therapies is unknown.
Objective: To compare treatment effectiveness of alemtuzumab vs natalizumab, fingolimod and interferon β.
Methods: 3936 patients (72% female, median follow-up 2.9 years, age 35, Expanded Disability Status Scale [EDSS] 2.5) from MSBase and MS centres in Cambridge, Cardiff, Bristol, Swansea, Dublin and Dresden were included. The inclusion criteria consisted of relapsing-remitting MS, on-treatment follow-up ⩾6 months, 1 baseline and 2 follow-up EDSS scores and availability of the minimum dataset. Three pairwise comparisons of alemtuzumab vs natalizumab, fingolimod or interferon were carried out. Propensity score was used to match on demographic and clinical characteristics, using 1:2 variable matching and 0.1 caliper. Multivariable clustered weighted models were used to compare annualised relapse rates (ARR; negative binomial model) or cumulative hazard of relapses, and 6-month confirmed EDSS progression or regression events (Andersen-Gill survival models). Six sensitivity analyses for matching strategy, inclusion of secondary progressive MS, or high pre-treatment ARR or prior on-treatment relapses were carried out.
Results: The included cohort consisted of 189, 2155, 828 and 1160 patients treated with alemtuzumab, interferon, fingolimod or natalizumab, respectively. Compared to interferon, alemtuzumab was associated with lower ARR (0.5 vs 0.2, p=10-16) and lower risk of EDSS progression and more likely EDSS reduction in patients with previously highly active MS (hazard ratio(HR)=4, p=0.02). Compared to fingolimod, ARR was lower on alemtuzumab (0.3 vs 0.15, p=10-11). Importantly, no differences in ARR (0.2 both groups, p=0.8) and EDSS progression were found between alemtuzumab and natalizumab. The likelihood of EDSS reduction was higher on natalizumab (HR=2.9, p=10-4). Sensitivity analyses largely confirmed the above results. Statistical power was sufficient to demonstrate clinically meaningful effects.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
Objective: To compare treatment effectiveness of alemtuzumab vs natalizumab, fingolimod and interferon β.
Methods: 3936 patients (72% female, median follow-up 2.9 years, age 35, Expanded Disability Status Scale [EDSS] 2.5) from MSBase and MS centres in Cambridge, Cardiff, Bristol, Swansea, Dublin and Dresden were included. The inclusion criteria consisted of relapsing-remitting MS, on-treatment follow-up ⩾6 months, 1 baseline and 2 follow-up EDSS scores and availability of the minimum dataset. Three pairwise comparisons of alemtuzumab vs natalizumab, fingolimod or interferon were carried out. Propensity score was used to match on demographic and clinical characteristics, using 1:2 variable matching and 0.1 caliper. Multivariable clustered weighted models were used to compare annualised relapse rates (ARR; negative binomial model) or cumulative hazard of relapses, and 6-month confirmed EDSS progression or regression events (Andersen-Gill survival models). Six sensitivity analyses for matching strategy, inclusion of secondary progressive MS, or high pre-treatment ARR or prior on-treatment relapses were carried out.
Results: The included cohort consisted of 189, 2155, 828 and 1160 patients treated with alemtuzumab, interferon, fingolimod or natalizumab, respectively. Compared to interferon, alemtuzumab was associated with lower ARR (0.5 vs 0.2, p=10-16) and lower risk of EDSS progression and more likely EDSS reduction in patients with previously highly active MS (hazard ratio(HR)=4, p=0.02). Compared to fingolimod, ARR was lower on alemtuzumab (0.3 vs 0.15, p=10-11). Importantly, no differences in ARR (0.2 both groups, p=0.8) and EDSS progression were found between alemtuzumab and natalizumab. The likelihood of EDSS reduction was higher on natalizumab (HR=2.9, p=10-4). Sensitivity analyses largely confirmed the above results. Statistical power was sufficient to demonstrate clinically meaningful effects.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
| Original language | English |
|---|---|
| Article number | 251 |
| Pages (from-to) | 829-832 |
| Number of pages | 4 |
| Journal | Multiple Sclerosis |
| Volume | 22 |
| Issue number | Supp: 3 |
| DOIs | |
| Publication status | Published - Sept 2016 |
| Externally published | Yes |
Keywords
- multiple sclerosis (MS)
- alemtuzumab
- natalizumab
- Patient outcomes