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#Post#: 1178--------------------------------------------------
(Abst.) Cochrane Database Review of alemtuzumab
DIR By: agate
Date: April 16, 2016, 11:28 pm
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From PubMed, April 16, 2016:
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> Cochrane Database Syst Rev. 2016 Apr 15;4:CD011203.
>
> Alemtuzumab for multiple sclerosis
>
> Riera R1, Porfírio GJ, Torloni MR.
>
>
> BACKGROUND:
>
> 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 exacerbations,
preventing new exacerbations and avoiding the progression of
disability. However, at present there is no effective treatment
that is capable of safely and effectively reaching these
objectives. This has led to the development and investigation of
new drugs.
>
> Recent clinical trials suggest that alemtuzumab, a humanised
monoclonal antibody against cell surface CD52, could be a
promising option for MS.
>
> OBJECTIVES:
>
> To assess the safety and effectiveness of alemtuzumab used
alone or associated with other treatments to decrease disease
activity in patients with any form of MS.
>
> SEARCH METHODS:
>
> We searched the Trials Register of the Cochrane Multiple
Sclerosis and Rare Diseases of the CNS Group (30 April 2015),
which contains trials from the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS and
the trial registry databases ClinicalTrials.gov and WHO
International Clinical Trials Registry Platform. There was no
restriction on the source, publication date or language.
>
> SELECTION CRITERIA:
>
> All randomised clinical trials (RCTs) involving adults
diagnosed with any form of MS according to the McDonald
criteria, comparing alemtuzumab alone or associated with other
medications, at any dose and for any duration, versus placebo or
any other active drug therapy or alemtuzumab in other dose,
regimen or duration. The co-primary outcomes were relapse-free
survival, sustained disease progression and number of
participants with at least one of any adverse events, including
serious adverse events.
>
> DATA COLLECTION AND ANALYSIS:
>
> Two independent review authors performed study selection, data
extraction and 'Risk of bias' assessment. A third review author
checked the process for accuracy.
>
> We used the Cochrane 'Risk of bias' tool to assess the risk of
bias of the studies included in the review. We used the GRADE
system to assess the quality of the body of evidence. To measure
the treatment effect on dichotomous outcomes we used the risk
ratio (RR); for the treatment effect on continuous outcomes, we
used the mean difference (MD) and for time-to-event outcomes we
used hazard ratio (HR). We calculated 95% confidence intervals
(CI) for these measures. When there was no heterogeneity, we
used a fixed-effect model to pool data.
>
> MAIN RESULTS:
>
> Three RCTs (1713 participants) fulfilled the selection
criteria and we included them in the review. All three trials
compared alemtuzumab versus subcutaneous interferon beta-1a for
patients with relapsing-remitting MS. Patients were
treatment-naive in the CARE-MS and CAMMS223 studies.
>
> The CARE-MS II study included patients with at least one
relapse while being treated with interferon beta or glatiramer
acetate. Alemtuzumab was given for 12 or 24 months; for some
outcomes, the follow-up period reached 36 months. The regimens
were (a) 12 mg or 24 mg per day administered intravenously, once
a day for five consecutive days at month 0 and 12 or (b) 24 mg
per day, intravenously, once a day for three consecutive days at
month 12 and 24.
>
> The patients in the other arm of the trials received
interferon beta-1a 44 μg subcutaneously three times weekly
after dose titration.At 24 months, alemtuzumab 12 mg was
associated with: (a) higher relapse-free survival (hazard ratio
(HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies,
moderate quality evidence); (b) higher sustained disease
progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191
participants; two studies; moderate quality evidence); (c) a
slightly higher number of participants with at least one adverse
event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two
studies; moderate quality evidence); (d) a lower number of
participants with new or enlarging T2-hyperintense lesions on
magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91;
1238 participants; two studies; I2 = 80%); and (e) a lower
number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248
participants; two studies, I2 = 29%; low quality evidence).
>
> At 36 months, alemtuzumab 24 mg was associated with: (a)
higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11
to 0.40; one study; 221 participants); (b) a higher sustained
disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69;
one study; 221 participants); and (c) no statistical difference
in the rate of participants with at least one adverse event.
>
> We did not find any study that reported any of the following
outcomes: rate of participants free of clinical disease
activity, quality of life, fatigue or change in the numbers of
MRI T2- and T1-weighted lesions after treatment. It was not
possible to perform subgroup analyses according to disease type
and disability at baseline due to lack of data.
>
> AUTHORS' CONCLUSIONS:
>
> In patients with relapsing-remitting MS, alemtuzumab 12 mg was
better than subcutaneous interferon beta-1a for the following
outcomes assessed at 24 months: relapse-free survival, sustained
disease progression-free survival, number of participants with
at least one adverse event and number of participants with new
or enlarging T2-hyperintense lesions on MRI.
>
> The quality of the evidence for these results was low to
moderate.
>
> Alemtuzumab 24 mg seemed to be better than subcutaneous
interferon beta-1a for relapse-free survival and sustained
disease progression-free survival, at 36 months.
>
> More randomised clinical trials are needed to evaluate the
effects of alemtuzumab on other forms of MS and compared with
other therapeutic options. These new studies should assess
additional relevant outcomes such as the rate of participants
free of clinical disease activity, quality of life, fatigue and
adverse events (individual rates, serious adverse events and
long-term adverse events). Moreover, these new studies should
evaluate other doses and durations of alemtuzumab course.
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