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The side effects can be nasty, but mitoxantrone can also be highly effective...



Mitoxantrone as induction treatment in aggressive relapsing remitting Multiple Sclerosis: treatment response factors in a 5-year follow-up observational study of 100 consecutive patients.

J Neurol Neurosurg Psychiatry. 2007 Sep 10
Emmanuelle LP E, Emmanuelle L E, Grégory T G, Marc C M, Jacques C J, Sean M S P, Gilles E G.
CHU Pontchaillou , RENNES, France.

BACKGROUND: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS).

OBJECTIVE: To report long-term effectiveness and safety of Mitoxantrone as induction therapy in Aggressive Relapsing Remitting MS patients and to assess treatment response factors. Material and

METHODS: 100 consecutive aggressive relapsing-remitting MS patients received Mitoxantrone 20 mg monthly combined with methylprednisolone 1g for 6 months. Relapses, EDSS and drug safety were assessed every 6 months up to at least 5 years. Within 6 months after induction, 73 patients received a maintenance therapy (Mitoxantrone every 3 months: 21; Interferon beta: 25; Azathioprine: 15; Methotrexate: 7; Glatiramer acetate: 5).

RESULTS: During the 12 months following Mitoxantrone start, the Annual Relapse Rate (ARR) was reduced by 91%, 78% of patients remained relapse-free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10-6) and 64% of patients improved by 1 point EDSS or more. At a longer term, the ARR reduction was sustained (0.29-0.42 up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved up-to 5 years. Younger age and lower EDSS at Mitoxantrone start were predictive of better treatment response. Three patients presented an asymptomatic decrease of the left ventricular ejection fraction under 50% (1 reversible). One patient was diagnosed with acute myeloid leukemia (remission 5 years after diagnostic).

CONCLUSION: Mitoxantrone monthly for 6 months as induction therapy followed by a maintenance treatment showed sustained clinical benefit up to 5 years with acceptable adverse events profile in patients with aggressive relapsing-remitting MS.

Pubmed URL

Dignan,

Good post. A similar study is being undertaken in the UK in Liverpool (run by Dr Boggild). For those with aggressive RR it provides another treatment option when the first line therapies aren't helping. I always like to see EDSS stability or improvement from treatments and side-effects which can be monitored / managed.

Ian

PS I hope you have forgiven me for trying to get you and jimmylegs together!

HI MEMBER MY NAME IS SEEVA I HAD VERY SEVERE PROGRESSIVE M.S IN ADDITION VERY BAD RELAPSES IN EARLY 1999 AND ONWARDS.EVERY TIME THE ATTACK I WAS WHEELCHAIR BOUND. AND ONLY ONE DRUG HELP ME OUT OF W.CHAIR WAS MITOXANTRON. MY NEURO IS THE ONE USING MOST FORVERY SEVERE M.S SUFFERS. IN SYDNEY. BUT ACCODING MY NEURO I HAVE USED THE MAXIMUM I CAN TAKE. SO ANY MORE ATTACK HE DOESNOT KNOW WHAT TO DO.I WILL SAY EVERY TIME I TOOK THE DRUG, FEWDAYS AFTER I WILL BE GOOD BALANCE AND BACK TO NOMAL. :roll:
SEEVA

Seeva, if Novantrone worked for you, pixantrone, which is in phase 2 trials, might be of interest. It is a very similar drug to Novantrone, but they tried to engineer out all (or at least most) of the cardio-toxicity that limits the use of Novantrone. The info below is from the US MS Society.



Agent: Pixantrone (BBR 2778)

Purpose of study: To test safety, control development of brain lesions and determine impact on immune function, also known as PIXAMS study

Possible mechanism: Intercalates DNA, inhibits topoisomerase II, cytotoxic

Study description: Open label

Dose/route: 4 courses Pixantrone 120 mg/m² iv at 3-week intervals

Outcome parameters: Immunosuppressive effects, Gd+ lesion evolution, safety

Type of MS: Aggressive RR or SP MS

Number of Subjects: 20

Start date: Fall 2007

Observation period: 2 years

Investigators: R. Gonsette and others Sites: Belgium National Centre for Multiple Sclerosis, Melsbroek, Belgium, and others, Europe

Results/Publications: Not available

Funding: Fondation-Charcot-Stichting

HI DIGNAN THANKS FOR YOUR IN FORMATION ABOUT NOVANTRONE. IT IS VERY USEFUL INFOMATION.
REGARDS
SEEVA :roll: