February 18, 2010
We've previously reported on imaging and surgical results suggesting that impaired blood drainage from the CNS is associated with MS (chronic cerebrospinal venous insufficiency, or CCSVI). One of the criticisms of this work is that it was conducted at a single center using ultrasound, a technique which can produce varying results across operators. So there have been calls for replication of this study, and as a result several centers have stepped up to answer these calls.
One of these centers, based at the University of Buffalo, has gotten off to a fast start and is reporting preliminary results from an imaging study that evaluated 500 people (MS subjects and controls). Participants in this study (Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD)) were imaged with both Doppler ultrasound and MRI. These preliminary results showed that 56% of the MS subjects and 22% of the controls met two of the five criteria developed to confirm CCSVI. These results were not quite as striking as the original results presented by Dr. Zamboni, which showed complete association of CCSVI with MS. However, they certainly are strong enough to compel further investigation in this area.
This preliminary report only gave a glimpse into the findings from this study; full results will be revealed at the next American Academy of Neurology meeting in April.
The first-line MS therapies (interferon beta and glatiramer acetate) have the benefit of long track records and good safety profiles, but they're not effective in everyone. Many of those who start one of these drugs but go on to have further relapses wind up switching therapies. However, another potential option is to add on another drug that might have a synergistic effect with the MS therapy. Recently two studies were reported that tested this strategy in people with MS who had tried interferon-beta but continued to have disease activity.
The CHOICE study was a 24-week, multi-center study that evaluated adding daclizumab to IFN-beta in people with MS. Daclizumab is a drug that is used to prevent rejection of transplanted tissues. It controls T cell expansion by binding to the CD25 molecule; this molecule is expressed by T cells and helps transmit signals that initiate cell division. In this study, 230 people who had been taking IFN-beta but who still had disease activity were randomized to added-on high-dose daclizumab, low-dose daclizumab, or placebo. The primary outcome of reducing the development of new or enlarged enhancing lesions was met, with the high-dose daclizumab group having on average only 1.32 of these events over the 24 weeks vs. 4.75 for the placebo group. This difference may be related to a 7-8 times increase in a type of immune cell called "CD56bright natural killer cells" for the daclizumab recipients vs. the placebo group. New trials to further evaluate daclizumab in MS are currently underway.
The ACTIVE trial studied adding on statins (namely, atorvastatin or Lipitor) to IFN-beta in people who had also been on IFN-beta for a while but continued to have relapses or new lesions. 45 people were randomized to IFN-beta plus statin (20 mg/day) or placebo and followed for 24 months. At the end of the study, the statin group had a significant reduction in enhancing lesions and relapses compared with baseline values, whereas the placebo group also had reductions in these measures but they were not significant. Other trials have assessed the impact of statins on MS before, with mixed results. Although this study was small in terms of numbers, it had the longest duration of any MS statin trial to date. A previous small study produced evidence that IFN-beta plus higher doses of atorvastatin may aggravate MS, but the ACTIVE study results showed the oppostive effect; this difference may be due to dose.