Key messages
– Alemtuzumab may reduce the risk of relapse and disease progression when compared to subcutaneous interferon beta-1a in people with relapsing–remitting MS, a type of MS where you have worsened symptoms (relapses) followed by a recovery period (remitting).
– Future well-designed studies are needed to assess patient-related outcomes such as quality of life and fatigue.
What is the issue?
Multiple sclerosis (MS) is a chronic disease of the nervous system that affects young and middle-aged adults. Repeated damage to the myelin sheaths (the membranes that cover and protect nerves) and other parts of the nerves can lead to serious disability. MS may be related to problems in the immune system. Alemtuzumab is a biological medicine (a type of antibody), which has already been used for other diseases.
What did we want to find out?
We aimed to investigate the benefits and unwanted effects (called adverse events) of alemtuzumab used alone or associated with other treatments for people with any form of MS. We wanted to find out if alemtuzumab was better compared to other available treatments for people with MS.
What did we do?
We searched for studies that investigated alemtuzumab for people with any form of MS. We searched the literature up to October 2020. We analyzed and compared the results of the included studies and assessed how much confidence we had in the available evidence.
What did we find?
We found three studies (including 1713 participants) that fulfilled the review selection criteria. All studies compared intravenous (injected into a vein) alemtuzumab versus subcutaneous (injected under the skin) interferon beta-1a for people with relapsing–remitting MS. Two studies (called CARE-MS I and CAMMS223) were treating the participants for their MS the first time (treatment-naive). The third study (CARE-MS II) included participants with at least one relapse while being treated with interferon beta or glatiramer acetate for at least six months.
Main results
The review of these studies found that, compared to subcutaneous interferon beta-1a, alemtuzumab may reduce the risk of relapse and disease progression (worsening of the MS) in people with relapsing–remitting MS, and make little to no difference in the proportion of participants with at least one adverse event (but both medicines had a high proportion of participants with at least one adverse event). There is a lack of information about the effects of alemtuzumab on other outcomes such as quality of life and fatigue.
What are the limitations of the evidence?
Our confidence in the effects of alemtuzumab, compared to interferon beta-1a, for the main outcomes ranges from low to very low. This means that there is a high probability that future studies could change our conclusions.
How up to date is the evidence?
The evidence is up to date to June 2022.
Compared with interferon beta-1a, alemtuzumab may improve relapse-free survival and sustained disease progression-free survival, and make little to no difference on the proportion of participants with at least one adverse event for people with relapsing–remitting MS at 36 months. The certainty of the evidence for these results was very low to low.
Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating and preventing exacerbations, and avoiding the progression of disability. At present, there is no treatment that is capable of safely and effectively reaching these objectives. Clinical trials suggest that alemtuzumab, a humanized monoclonal antibody, could be a promising option for MS.
To evaluate the benefits and harms of alemtuzumab alone or associated with other treatments in people with any form of MS.
We used standard, extensive Cochrane search methods. The latest search date was 21 June 2022.
We included randomized controlled trials (RCTs) in adults with any subtype of MS comparing alemtuzumab alone or associated with other medications versus placebo; another active drug; or alemtuzumab in another dose, regimen, or duration.
We used standard Cochrane methods. Our co-primary outcomes were 1. relapse-free survival, 2. sustained disease progression, and 3. number of participants experiencing at least one adverse event. Our secondary outcomes were 4. participants free of clinical disability, 5. quality of life, 6. change in disability, 7. fatigue, 8. new or enlarging lesions on resonance imaging, and 9. dropouts. We used GRADE to assess certainty of evidence for each outcome.
We included three RCTs (1713 participants) comparing intravenous alemtuzumab versus subcutaneous interferon beta-1a for relapsing–remitting MS. Participants were treatment-naive (two studies) or had experienced at least one relapse after interferon or glatiramer (one study). Alemtuzumab was given at doses of 12 mg/day or 24 mg/day for five days at months 0 and 12, or 24 mg/day for three days at months 12 and 24. Participants in the interferon beta-1a group received 44 μg three times weekly.
Alemtuzumab 12 mg: 1. may improve relapse-free survival at 36 months (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.18 to 0.53; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.25, 95% CI 0.11 to 0.56; 1 study, 223 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (risk ratio [RR] 1.00, 95% CI 0.98 to 1.02; 1 study, 224 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (mean difference [MD] −0.70, 95% CI −1.04 to −0.36; 1 study, 223 participants; low-certainty evidence). The evidence is very uncertain regarding the risk of dropouts at 36 months (RR 0.81, 95% CI 0.57 to 1.14; 1 study, 224 participants; very low-certainty evidence).
Alemtuzumab 24 mg: 1. may improve relapse-free survival at 36 months (HR 0.21, 95% CI 0.11 to 0.40; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.33, 95% CI 0.16 to 0.69; 1 study, 221 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (RR 0.99, 95% CI 0.97 to 1.02; 1 study, 215 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (MD −0.83, 95% CI −1.16 to −0.50; 1 study, 221 participants; low-certainty evidence); 5. may reduce the risk of dropouts at 36 months (RR 0.08, 95% CI 0.01 to 0.57; 1 study, 215 participants; low-certainty evidence).
For quality of life, fatigue, and participants free of clinical disease activity, the studies either did not consider these outcomes or they used different measuring tools to those planned in this review.