Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis

Background: Interferon beta treatment is only partially effective in multip le sclerosis (MS) suggesting a potential role for adjunctive therapies. Ret inoids can augment the clinical efficacy of type 1 inteferons in patients w ith 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 ad ded to peripheral blood mononuclear cells from untreated patients with MS o r from controls potentiates this ability of interferon beta-1b to augment C D8 suppressor cell function in vitro. Objective: To determine whether retinoid administration to patients with MS who are being treated with interferon beta-lb augments their CD8 suppresso r cell function. Setting: A university hospital MS clinic. Particpants Patients with MS who were being treated with interferon beta-1b, 14 patients with secondary prog ressive 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 mouth, 25 m s twice daily for the second and third months, and 10 mg twice daily therea fter. The 25-mg tu ice daily dose was not well tolerated and of the 14 pati ents who remained in the phase 1 clinical trial through month 3 dose reduct ion to 10 mg thrice daily was required in 1 patient and to 10 mg twice dail y in 4 patients. Eleven patients completed the trial. Etretinate treatment significantly augmented suppressor function over baseline values at 1, 3, a nd 6 months. No meaningful change was noted in disability or quality of lif e over the course of the phase 1 clinical trial. Neuropsychological testing of computers 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 d aily augments suppressor cell function in patients with MS receiving interf eron beta-lb. Higher dose etretinate treatment (25 mg twice daily) is poorl y tolerated by patients with MS. Even at 10 mg twice daily adverse experien ces involving the mucous membranes and the skin become troublesome for some , but not all, patients. Whether pulse therapy or administration of retinoi d restricted to the day of interferon beta dosing will also augment suppres sor function, while being better tolerated, remains to be determined.