Addition of oral methylprednisolone (MP) the standard treatment of subcutaneous interferon beta-1a (IFB1a) substantially reduces the relapse rate in patients with relapsing-remitting multiple sclerosis (RRMS). The findings are reported in an Article published Online First and in the June edition of The Lancet Neurology, and linked to the findings of a similar study being announced at the American Academy of Neurology meeting in Seattle, USA.*
Like other treatments for MS, IFB1a is only partly effective, and second-line therapies (mitoxantrone and natalizumab) with enhanced effectiveness can have serious side-effects eg, mitoxantrone can cause leukaemia in 1 per 150 patients treated. Thus, new safe and effective treatments are needed. This study (the NORMIMS** trial) analysed 130 patients with RRMS in 29 centres in Denmark, Norway, Sweden, and Finland, and was carried out by Dr Per Soelberg Sorensen, Danish Multiple Sclerosis Research Center, Rigshospitalet, Copenhagen, Denmark, and colleagues. Each patient had had at least one relapse in the previous 12 months, and was being treated with subcutaneous IFB1a. Patients were randomised to receive, in addition to IFB1a, 200mg of oral MP (66 patients) or matching placebo (64) on five consecutive days, every four weeks for 96 weeks.
The researchers found that a high number of patients had withdrawn from the study before week 96 (26% of MP group, 17% of placebo group). MP group withdrawals were mainly because of side-effects, and those from the placebo group mainly because of lack of effect. The mean yearly relapse rate was 22% in the MP group, versus 59% in the placebo group — and was thus nearly three times higher for placebo patients compared with MP patients. Sleep disturbance and neurological and psychiatric symptoms were the most frequent side-effects recorded in the MP group; but bone mineral density (which can be reduced with prolonged therapy with glucocorticoids such as MP) had not changed after 96 weeks.
The authors conclude: "Oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in relapse rate. However, because of the small number of patients and the high dropout rate, these findings need to be corroborated in larger cohorts."
In an accompanying Reflection and Reaction comment, Dr Jeffrey A Cohen, Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Ohio, USA, says that despite the results from NORMIMS, whether or not addition of oral MP to IFB1a improves outcomes for RRMS patients remains uncertain. This will remain the case until the findings of the MECOMBIN study — which is a similar trial in a larger number of patients — are published . These results from MECOMBIN will be announced at the AAN meeting at the same time as NORMIMS is published by The Lancet Neurology on www.thelancet.com (See above for embargo).
Dr Per Soelberg Sorensen, Danish Multiple Sclerosis Research Center, Rigshospitalet, Copenhagen, Denmark (attending AAN meeting) T) +45 40303545 E) pss@rh.dk
For Dr Jeffrey A Cohen, Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Ohio, USA (who is attending AAN meeting) please contact Molly Johnson T) +1 216-312-9253 E) johnsm@ccf.org / cohenj@ccf.org
For full Article and Reflection and Reaction, see: http://press.thelancet.com/tlnnormims.pdf
Notes to editors: *The AAN meeting is taking place from April 25 to May 2 at Washington State Convention and Trade Center, Seattle, USA. For media information on the MECOMBIN study, please contact Angela Babb, +1 651 695-2789, ababb@aan.com; Jenine Anderson, +1 651 695-2738, janderson@aan.com ; AAN Press Room 307/308 (April 25–May 1): + 1 206 219-4730.
**NORMIMS = nordic trial of oral methylprednisolone as add-on therapy to interferon beta-1a for treatment of relapsing-remitting multiple sclerosis
Journal
The Lancet Neurology