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« : 09 Temmuz 2008 - 21:45:50 » |
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40 PPMS hastasi uzeinde LDN calismasi yapildi. Bu hastalarin beta-endorphins derecelerinin dusuk oldugu biliniyordu. Bu yuzden, MS icin kullanmakta oldugumuz guclu ilaclarin, beyindeki kan duvarindan (blood brain barrier) sizamadiklari saniliyor.
Primary Progressive hastasi olan 40 hastayla yapilan 32 haftalik calisma suresinde, LDN tedavisi alanlarda, beta-endorphins derecesi artti. Boylece LDN tedavisinde kullanilan ilacin, beyindeki kan duvarindan (blood brain barrier) sizabildigi dusunuluyor.
Not: Bizim kullandigimiz ilaclarda, ozellikle Betaferonlarda, amac beta-interferon degerimizi yuksek tutmak. Beta-interferonun, vucuttaki iltihaplanmalar icin tedavi edici ozelligi vardir.
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Relapsing-Remitting hastalari uzerinde, Laquinimod ve Placebo ilaclariyla yapilan denemelerde, Laquinimod ilacinin, MS uzerinde %40'lik bir tedavisi oldugu aciklandi.
Laquinimod ile tedavi olanlara, hergun 0.6 mg doz uygulandi. Yapilan MR kiyaslamasinda, bu arastirma, genisleyen plak averaji 2.6 olan Laquinimod kullanicilari ile 4.2 olan Placebo kullanicilari arasinda yapildi.
Laquinimod kullananlarda, yeni plak olusumu %50 engellendi.
Calismalar 36 hafta surdu ve 24., 28., 32. ve 36. haftalarda MR cekildi.
Ayrica, Laquinimod 0.3 doz kullanlarda, yeni plak olusumunda baskilayici bir gorev goruldugu aciklandi ve her 2 ayri doz uzerinde degerlendirme firsati elde edildi.
Calisma 306 relapsing-remitting hastasi uzerinde, ayrica en az 1 atak geciren ve beyninde 1 genisleyen plak bulunan hastalarda, 9 ulkenin, 51 merkezinde yapildi.
Laquinimod 0.3 doz kullaniminda elde edilen tedavi gucunun, Placeboya gore o kadar da onemli olmadigi aciklandi. (genisleyen plak averaji Laquinimod/3.9 ve Placebo/2.6)
Son 4 MR'da, Laquinimod 0.6 dozu, Placeboya gore %55 yeni plak gelisiminde azalma sagladi. (genisleyen plak averaji Laquinimod/4.0 ve Placebo/9.0)
12. ile 36. haftaya kadar olan calismada, Laquinimod 0.6 dozu kullananlarda, genis duzeyde olan plaklarda %51 (genisleyen plak averaji Laquinimod/2.7 ve Placebo/4.4), orta duzeyde olan plaklarda %60 (genisleyen plak averaji Laquinimod/6.0 ve Placebo/15.0) azalma goruldu.
Laquinimod 0.6 dozu kullananlarda, Placeboya gore %70.8'e %62.7 atak gecirmeme durumu goruldu.
Laquinimod 0.3 ve 0.6 dozlari guvenilir bulundu. Kisa sureli karaciger enzimi artisi tesbit edildi.
(20 Haziran 2008)
LDN Trial in Primary Progressive Multiple Sclerosis
A pilot study of LDN therapy in MS was carried out by the Milan neurological researcher, Dr. Maira Gironi in 2007.
Dr. Gironi’s research team has long been a locus for significant research on endorphins in relation to illness, and this study tracked accurate assessments of the patients’ beta-endorphin levels in response to their LDN treatment.
This was a 6-month pilot, multicentric, open-label, therapeutic study of 40 patients with Primary Progressive Multiple Sclerosis (PPMS) between the age of 18 and 60. The subjects were over 3 and less than 6 on the expanded disability severity scale (EDSS). They were affected with spasticity, pain, and/or fatigue. Optimisation of gabaergic or serotoninergic drugs before entering the study was requested. Any opioid-containing drug, immunosuppressive or immunomodulator medicines were not allowed.
All 40 patients were treated with LDN at a final dose of 5 mg after a 2-week titration of 2.5 mg. Common involvement of the spinal cord mostly in the primary progressive form of MS explains a high prevalence of spasticity, pain, and fatigue accompanying the disease. People with PPMS are known to have low levels of beta-endorphins and a possible mild, diffuse inflammatory reaction. Conventional anti-inflammatory drugs seem to fail to cross the blood brain barrier in people with PPMS.
During the 32 weeks of the study, participants underwent periodic clinical and biomedical analyses to evaluate any adverse events. Neurological evaluations, using scales of spasticity, pain, and fatigue, were periodically performed. The measurement of peripheral blood mononuclear cells’ beta-endorphin levels both before and after treatment were used to confirm or deny the supposed increase of this opioid during LDN treatment. An LDN-driven increase in beta-endorphins was expected to have an anti-inflammatory effect. This would suggest that LDN can cross the blood brain barrier.
The treatment phase of the study was completed, as scheduled, in Autumn 2007, analysis of the data is ongoing.
Dr. Gironi and her colleagues presented a poster summary of their 6-month study of LDN for Primary Progressive MS to the AAN conference in Chicago in April 2008.
The open label study used a 5mg dosage of LDN in 40 patients. There were 5 dropouts, most of which appeared unrelated to the drug. Endorphin levels were measured at intervals and were seen to gradually increase throughout. This correlated with a general trend of improvement in a number of efficacy measures. Significant improvements were seen by the study’s conclusion in both fatigue and depression.
Common adverse events reported during the study were urinary tract infections, some increases in liver enzymes, mild agitation and sleep disturbance. To date no serious adverse events have been reported for the study.
Full study results are awaited and expected be published in a relevant medical journal. (20/06/08)
Laquinimod shows great promise in Multiple Sclerosis trial
Laquinimod, a new type of immumodulatory agent for relapsing-remitting multiple sclerosis, led to a 40% reduction in lesions, according to results of a multicenter, placebo-controlled phase IIb trial.
Patients treated with laquinimod at a dose of 0.6 mg a day averaged 2.6 gadolinium-enhancing lesions on MRI compared with 4.2 for the placebo group (P=0.0048) as reported by Giancarlo Comi, M.D., of the University Vita-Salute and colleagues in the June issue of The Lancet.
The between-group difference emerged early in the trial, and follow-up beyond the primary study period demonstrated even larger reductions in MRI-detected lesions with laquinimod versus placebo.
Additionally, the number of new lesions was reduced by 50% in the laquinimod group.
"The decrease of MRI activity during the last part of the study was evidence for both gadolinium-enhancing and new T2 lesions, indicating that laquinimod reduces not only the extent of blood-brain barrier opening, but also the accrual of fixed lesions," the authors said.
Available therapies for multiple sclerosis all target inflammatory aspects of the disease. In addition, all of the approved therapies require injection, creating a potential advantage for any oral agent.
Laquinimod is structurally related to linomide, a drug that reduced disease activity in MS but had unacceptable toxicity, the authors said. Preclinical and phase I clinical studies suggested laquinimod had greater activity and a more favourable safety profile compared with linomide.
In a previous 24-week, randomized phase II study, laquinimod 0.3 mg/d suppressed formation of new MS lesions and was well tolerated. Those results led to the current evaluation of two different doses of the drug.
The study involved 306 patients relapsing-remitting multiple sclerosis with who had had one or more relapses in the previous year and at least one gadolinium-enhancing lesion on screening MRI. Investigators at 51 centers in nine countries randomized the patients to placebo or to laquinimod 0.3 mg/d or 0.6 mg/d.
The trial lasted 36 weeks, and the primary outcome was the cumulative total of gadolinium-enhancing lesions from the final four MRI scans at weeks 24, 28, 32, and 36.
Compared with placebo, laquinimod 0.6 mg reduced the average number of lesions per scan on the final four MRI scans by 40.4%.
The 0.3 mg dose did not significantly reduce the number of lesions compared with placebo (3.9 versus 2.6).
Comparison of the median cumulative number of lesions from the last four MRI scans resulted in a 55% reduction in the number of lesions with laquinimod 0.6 mg versus placebo (4.0 versus 9.0).
The number of new T2 lesions on the last four scans was 44% lower with laquinimod 0.6 mg (P=0.0013), and the number of new T1-hypointense lesions was 51% lower in the laquinimod 0.6 mg group (P=0.0064).
Examination of MRI scans from weeks 12 through 36 demonstrated a 51% reduction in the mean number of gadolinium-enhancing lesions with laquinimod 0.6 mg (2.7 versus 4.4) and a 60% decrease in the median number of lesions (6.0 versus 15.0).
Patients in the laquinimod 0.6 mg group had an annualized relapse rate of 0.52 compared with 0.77 for those on placebo which was not statistically significant (P=0.0978). Additionally, 70.8% of laquinimod 0.6 mg patients were relapse-free compared with 62.7% of the placebo group.
Both doses of laquinimod were well tolerated. The primary treatment-related effect was a transient, dose-related increase in liver enzymes, the authors said.
Source: The Lancet - Comi G, et al "Effect of laquinimod on MRI-monitored disease activity in aptients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, placebo-controlled phase IIb study" Lancet 2008; 371: 2085-2092. (20/06/08)
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