NEW YORK (Reuters Health) – Daclizumab added to ongoing interferon-beta treatment further decreases multiple sclerosis disease activity, according to a multicenter phase II trial reported online February 16 in The Lancet Neurology.
Daclizumab is an anti-CD25 monoclonal antibody that increases levels of CD56(bright) natural killer cells, believed to cause cell-mediated lysis of autologous activated T cells.
Dr. John W. Rose and co-researchers conducted their randomized, double-blind trial at 51 centers in North America and Europe. The 230 study subjects were on a stable interferon-beta regimen, and 212 had the relapsing-remitting form of the disease. Each subject had at least one gadolinium contrast-enhancing lesion of the brain or spinal cord and/or at least one relapse in the year prior to enrollment. Mean age was 39.8 years.
The authors randomized 75 patients to high-dose subcutaneous daclizumab (2 mg/kg every 2 weeks), 78 to low-dose daclizumab (1 mg/kg every 4 weeks), and 77 to placebo. All continued to take interferon-beta. After the 24-week active treatment phase, the researchers followed patients for an additional 48 weeks for safety purposes.
An enlarged gadolinium contrast-enhancing lesion was defined as an increase in size of at least 50% for lesions less than 5 mm in diameter or at least 20% for larger lesions.
The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the placebo group, 1.32 in the high-dose daclizumab group (p = 0.004), and 3.58 in the low-dose group (p = ns).
The corresponding mean increases in total volume of such lesions between weeks 8 and 24 were 453 mm3, 140 mm3 (p = 0.046), and 352 mm3 (p = ns).
The annualized relapse rate was 0.86 in the placebo group, 0.49 in the high-dose group, and 0.58 in the low-dose group, but the differences were not statistically significant.
When treatment stopped, lesion formation returned to roughly baseline levels. The number of CD25+ T cells fell by 25% during daclizumab treatment but also returned to pretreatment levels after the active treatment phase.
The same was true for CD56(bright) natural killer cells, which rose 7- to 8-fold during treatment in both daclizumab groups. As the quartile ranking of CD56(bright) cell counts increased, the formation of lesions decreased (p = 0.006 for trend).
These findings, the researchers point out, support the theory that expansion of CD56(bright) cells mediates some of the effects of daclizumab on multiple sclerosis lesion activity.
The authors report that daclizumab was well tolerated, with the number of common adverse events, including infections, generally equal across groups. There were more grade 3 events associated with daclizumab, but these resolved with standard interventions.
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