Avonex plus Doxycycline trial preliminary results
Posted: Wed Apr 05, 2006 8:55 am
An abstract from the AAN meeting about the combination trial of doxycycline and Avonex. The preliminary, small sample results look promising.
Combination Therapy with Intramuscular Interferon Beta-1a and Oral Doxycycline in Patients with Multiple Sclerosis: An Open-Label Trial
Alireza Minagar, J. Steven Alexander, Rhonda Brooks, Roger E. Kelley, Robert N. Schwendimann, Eduardo Gonzalez-Toledo, Dana Merrill Bryan, Shreveport, LA
OBJECTIVE: To determine the safety, tolerability, and efficacy of doxycycline combined with intramuscular (IM) interferon beta-1a (IFNb-1a) in multiple sclerosis (MS) patients experiencing breakthrough disease
BACKGROUND: Doxycycline is a potent matrix metalloproteinase (MMP) inhibitor that can potentially suppress destruction of the extracellular matrix and therefore limit the transendothelial migration of activated leukocytes in MS. Additionally, because MMP-9 is capable of cleaving IFNB potentially contributing to relapses during therapy, doxycycline may be expected to reduce the frequency of relapses
DESIGN/METHODS: This was an open-label, single-center, single-arm, cross-over study. Patients aged 18 to 55 years with relapsing MS, an EDSS score of 1.5 to 4.5, one or more gadolinium-enhancing (Gd+) lesions on MRI, continuous treatment with IM IFNb-1a for a minimum of 6 months, and a relapse within 60 days of their baseline visit (month 3) were eligible. Patients underwent MRIs at months -3, -2, -1, 0, +1, +2, +3. Daily oral doxycycline 100 mg combined with weekly IM IFNb-1a 30 mcg, began at month 0
RESULTS: To date, 15 patients have been enrolled and 11 have completed the study. The patients had a mean age of 42.013.3 years and 9 were female. An interim analysis included 11 patients with 1 pre-treatment and 1 on-treatment MRI and neurologic examination. During pretreatment (months 3, -2, -1, and 0), the mean number of Gd+ lesions was 10.36.6, decreasing to 6.25.4 during combination therapy (p=0.001). Mean pretreatment EDSS was 3.90.4 decreasing to 1.40.5 (p=0.001) during treatment. One patient had transiently elevated hepatic enzymes on combination therapy, none have withdrawn. Final results of MRI and clinical measures will be presented
CONCLUSIONS/RELEVANCE: Combination therapy with doxycycline 100 mg daily and IM IFNb-1a 30 mcg weekly appears to be safe and effective in patients with relapsing MS.
Combination Therapy with Intramuscular Interferon Beta-1a and Oral Doxycycline in Patients with Multiple Sclerosis: An Open-Label Trial
Alireza Minagar, J. Steven Alexander, Rhonda Brooks, Roger E. Kelley, Robert N. Schwendimann, Eduardo Gonzalez-Toledo, Dana Merrill Bryan, Shreveport, LA
OBJECTIVE: To determine the safety, tolerability, and efficacy of doxycycline combined with intramuscular (IM) interferon beta-1a (IFNb-1a) in multiple sclerosis (MS) patients experiencing breakthrough disease
BACKGROUND: Doxycycline is a potent matrix metalloproteinase (MMP) inhibitor that can potentially suppress destruction of the extracellular matrix and therefore limit the transendothelial migration of activated leukocytes in MS. Additionally, because MMP-9 is capable of cleaving IFNB potentially contributing to relapses during therapy, doxycycline may be expected to reduce the frequency of relapses
DESIGN/METHODS: This was an open-label, single-center, single-arm, cross-over study. Patients aged 18 to 55 years with relapsing MS, an EDSS score of 1.5 to 4.5, one or more gadolinium-enhancing (Gd+) lesions on MRI, continuous treatment with IM IFNb-1a for a minimum of 6 months, and a relapse within 60 days of their baseline visit (month 3) were eligible. Patients underwent MRIs at months -3, -2, -1, 0, +1, +2, +3. Daily oral doxycycline 100 mg combined with weekly IM IFNb-1a 30 mcg, began at month 0
RESULTS: To date, 15 patients have been enrolled and 11 have completed the study. The patients had a mean age of 42.013.3 years and 9 were female. An interim analysis included 11 patients with 1 pre-treatment and 1 on-treatment MRI and neurologic examination. During pretreatment (months 3, -2, -1, and 0), the mean number of Gd+ lesions was 10.36.6, decreasing to 6.25.4 during combination therapy (p=0.001). Mean pretreatment EDSS was 3.90.4 decreasing to 1.40.5 (p=0.001) during treatment. One patient had transiently elevated hepatic enzymes on combination therapy, none have withdrawn. Final results of MRI and clinical measures will be presented
CONCLUSIONS/RELEVANCE: Combination therapy with doxycycline 100 mg daily and IM IFNb-1a 30 mcg weekly appears to be safe and effective in patients with relapsing MS.