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Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis
Z X Qu1, N Pliskin, M W Jensen
1University of Chicago, Department of Neurology, 5841 S Maryland Ave, MC 2030, Chicago, IL 60637, USA.
Archives of Neurology
|February 15, 2001
Summary
Adding retinoids like etretinate to interferon beta-1b treatment for multiple sclerosis (MS) can enhance CD8 suppressor cell function. Lower doses of etretinate were better tolerated and showed benefits in MS patients.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Interferon beta (IFN-β) therapy for multiple sclerosis (MS) has limited efficacy, necessitating exploration of adjunctive treatments.
- Retinoids have shown potential to enhance type 1 interferon efficacy in cancer and may offer similar benefits in MS.
- In vitro studies indicate that IFN-β-1b can partially reverse CD8 suppressor cell defects in MS, an effect potentiated by all-trans retinoic acid.
Purpose of the Study:
- To investigate whether retinoid administration augments CD8 suppressor cell function in patients with MS undergoing interferon beta-1b treatment.
- To assess the tolerability and potential impact on disability and quality of life of etretinate in MS patients.
Main Methods:
- A phase 1 clinical trial conducted at a university hospital MS clinic.
- Seventeen patients with MS (14 secondary progressive, 3 relapsing-remitting) receiving interferon beta-1b were treated with etretinate for up to 6 months.
- Dosing involved escalating and then reducing etretinate based on tolerability, with CD8 suppressor cell function, disability, quality of life, and neuropsychological tests assessed.
Main Results:
- Etretinate treatment, particularly at lower doses (10 mg BID/TID), significantly augmented CD8 suppressor cell function compared to baseline at 1, 3, and 6 months.
- Higher dose etretinate (25 mg BID) was poorly tolerated, leading to dose reductions in several patients.
- No significant changes in disability or quality of life were observed, though some completers showed improvements in verbal memory.
Conclusions:
- Low-dose etretinate (10 mg BID/TID) effectively augments suppressor cell function in MS patients on interferon beta-1b.
- Higher doses of etretinate are not well-tolerated, and even lower doses can cause side effects like skin and mucous membrane issues.
- Further research is needed to explore alternative retinoid administration strategies, such as pulse therapy, for better tolerability and sustained efficacy.
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