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Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in
Abstract:
The central nervous system lesions of multiple sclerosis (MS) can be detected by magnetic resonance imaging (MRI) and the initial perivascular inflammatory component is distinguished by the presence of gadolinium enhancement. To assess the effect of systemic lymphocyte depletion on disease activity, seven patients with MS received a 10-day intravenous course of the humanised monoclonal antibody CAMPATH-1H (anti-CDw52). With some variations in the protocol, enhanced cerebral MR images were obtained monthly for 3-4 months before and at least 6 months after treatment. 28 enhancing areas were detected on the first series of 7 scans; 51 additional active lesions were identified on 18 scans before treatment; 15 were detected on 20 scans done over the next 3 months, but only 2 active lesions were seen on 23 scans during follow-up beyond 3 months. The difference in lesion incidence rate before and after treatment varied and the rate ratio was significantly reduced in only three patients. Collectively, in a "meta-analysis", the rate ratios were 0.15 [corrected] (95% CI 0.09-0.24) for all seven patients and 0.24 (0.14-0.42; p < 0.001) with exclusion of the patient whose scanning schedule differed. The effect of CAMPATH-1H on disease activity provides direct, but preliminary, evidence that disease activity in MS depends on the availability of circulating lymphocytes and can be prevented by lymphocyte depletion. It is too early to say anything about the clinical results of treatment with this agent.
Insights
Systemic lymphocyte depletion using CAMPATH-1H significantly reduced multiple sclerosis (MS) disease activity, as shown by fewer active lesions on MRI scans. This suggests circulating lymphocytes are crucial for MS progression.
Area of Science:
- Neuroimmunology
- Clinical Neurology
Background:
- Multiple sclerosis (MS) involves central nervous system lesions detectable by MRI.
- Gadolinium enhancement on MRI indicates active inflammation in MS.
Purpose of the Study:
- To evaluate the impact of systemic lymphocyte depletion on MS disease activity.
- To assess the efficacy of CAMPATH-1H (anti-CDw52) in reducing inflammatory lesions.
Main Methods:
- Seven MS patients received a 10-day intravenous course of CAMPATH-1H.
- Enhanced cerebral MRI scans were performed monthly before and after treatment for 3-6 months.
- Lesion incidence rates were compared pre- and post-treatment.
Main Results:
- A significant reduction in active MRI lesions was observed after CAMPATH-1H treatment.
- The rate ratio for new lesions decreased substantially post-treatment (0.15 overall, 0.24 excluding one patient).
- Preliminary evidence suggests lymphocyte depletion halts MS disease activity.
Conclusions:
- CAMPATH-1H treatment effectively reduces MS disease activity.
- Circulating lymphocytes play a key role in MS pathogenesis.
- Further research is needed to determine clinical outcomes.