Lymphocyte clue to multiple sclerosis drug response

By Eleanor McDermid, Senior medwireNews Reporter

Patients with rapid recovery of CD4-positive T cells after alemtuzumab treatment for multiple sclerosis (MS) are at risk for disease progression or relapse, research suggests.

The difference was apparent from 3 months after treatment, implying the potential for individualized treatment protocols based on CD4+ counts, say lead researcher Neil Robertson (Cardiff University, UK) and colleagues.

"The association between disease activity and early lymphocyte recovery is not surprising, as MS is primarily a cell-mediated disorder," they write in Neurology. "However, this relationship has not been demonstrated in vivo before."

The researchers assessed 56 patients (40 women) given alemtuzumab 12 mg daily for 5 days to treat symptoms of MS. They observed an initial "profound depletion" of lymphocyte subsets, followed by gradual recovery.

CD19+ cells were the first to recover, reaching the 25th percentile of average pretreatment levels at 3-6 months after treatment. These were followed by CD8+ cells, which reached a similar level after 6-9 months.

Patients' average CD4+ cell counts remained below the 25th of pretreatment levels for up to 24 months of follow up (they received a second alemtuzumab course 12 months after initial treatment). However, recovery of CD4+ cells differed between patients who did and did not exhibit disease activity during follow up.

In all, eight patients had a relapse, five had progressive disability, and four had asymptomatic lesions on magnetic resonance imaging. CD4+ cells were significantly higher at 6 and 24 months in patients with than without clinical relapse, and in those with than without new lesions.

CD4+ counts diverged from 3 months between patients who remained stable and those with any clinical or imaging measure of new disease activity, remaining significantly higher in those with disease activity through 24 months.

Having a 12-month CD4+ count above 400x10⁶/mL was 81.1% sensitive and 73.7% specific for new disease activity by 24 months. "Current practice is to routinely image all patients at 24 months and to base treatment decisions on these scans and available clinical data," say Robertson et al.

They note that the high negative predictive value of a low CD4+ count suggests that retreatment could potentially be restricted to patients with higher counts. "Inevitably this would be attractive in managed care programs and environments where access to imaging is difficult and this economic argument could be built on if larger studies support this assertion."

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