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Etretinate Augments Interferon Beta-1b Effects on Suppressor Cells in Multiple Sclerosis
Zhi Xiang Qu, PhD;
Neil Pliskin, PhD;
Mark W. Jensen, PhD;
David White, PhD;
Barry G. W. Arnason, MD
Arch Neurol. 2001;58:87-90.
Background Interferon beta treatment is only partially effective in multiple sclerosis
(MS) suggesting a potential role for adjunctive therapies. Retinoids can augment
the clinical efficacy of type 1 interferons in patients with cancer. We reasoned
that the same might hold in MS. Interferon beta-1b added to peripheral blood
mononuclear cells in vitro partially reverses the CD8 suppressor cell defect
of patients with MS. All-trans retinoic acid added to peripheral
blood mononuclear cells from untreated patients with MS or from controls potentiates
this ability of interferon beta-1b to augment CD8 suppressor cell function
in vitro.
Objective To determine whether retinoid administration to patients with MS who
are being treated with interferon beta-1b augments their CD8 suppressor cell
function.
Setting A university hospital MS clinic.
Participants Patients with MS who were being treated with interferon beta-1b, 14
patients with secondary progressive MS and 3 patients with relapsing remitting
MS.
Results Seventeen patients with MS received etretinate treatment for up to 6
months. Planned dosing was 10 mg 3 times daily for the first month, 25 mg
twice daily for the second and third months, and 10 mg twice daily thereafter.
The 25-mg twice daily dose was not well tolerated and of the 14 patients who
remained in the phase 1 clinical trial through month 3 dose reduction to 10
mg thrice daily was required in 1 patient and to 10 mg twice daily in 4 patients.
Eleven patients completed the trial. Etretinate treatment significantly augmented
suppressor function over baseline values at 1, 3, and 6 months. No meaningful
change was noted in disability or quality of life over the course of the phase
1 clinical trial. Neuropsychological testing of completers suggested improvement
on selected aspects of verbal memory at 6 months compared with baseline values.
Conclusions Etretinate treatment at a dose of 10 mg twice or three times daily augments
suppressor cell function in patients with MS receiving interferon beta-1b.
Higher dose etretinate treatment (25 mg twice daily) is poorly tolerated by
patients with MS. Even at 10 mg twice daily adverse experiences involving
the mucous membranes and the skin become troublesome for some, but not all,
patients. Whether pulse therapy or administration of retinoid restricted to
the day of interferon beta dosing will also augment suppressor function, while
being better tolerated, remains to be determined.
From the Departments of Neurology (Drs Qu, Pliskin, Jensen, White,
and Arnason) and Psychiatry (Dr Pliskin) and the Brain Research Institute
(Drs Pliskin and Arnason), University of Chicago, Chicago Ill. The authors
have no commercial, proprietary, or financial interest in the products and
companies described in this article.
Reprints: Barry G. W. Arnason, MD, University of Chicago, Department
of Neurology, 5841 S Maryland Ave, MC 2030, Chicago, IL 60637.
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