Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy.

Abstract

OBJECTIVE:

To assess the current use of glucocorticoids (GCs) in Duchenne muscular dystrophy in the UK, and compare the benefits and the adverse events of daily versus intermittent prednisolone regimens.

DESIGN:

A prospective longitudinal observational study across 17 neuromuscular centres in the UK of 360 boys aged 3-15 years with confirmed Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off) prednisolone for a mean duration of treatment of 4 years.

RESULTS:

The median loss of ambulation was 12 years in intermittent and 14.5 years in daily treatment; the HR for intermittent treatment was 1.57 (95% CI 0.87 to 2.82). A fitted multilevel model comparing the intermittent and daily regiments for the NorthStar Ambulatory Assessment demonstrated a divergence after 7 years of age, with boys on an intermittent regimen declining faster (p<0.001). Moderate to severe side effects were more commonly reported and observed in the daily regimen, including Cushingoid features, adverse behavioural events and hypertension. Body mass index mean z score was higher in the daily regimen (1.99, 95% CI 1.79 to 2.19) than in the intermittent regimen (1.51, 95% CI 1.27 to 1.75). Height restriction was more severe in the daily regimen (mean z score -1.77, 95% CI -1.79 to -2.19) than in the intermittent regimen (mean z score -0.70, 95% CI -0.90 to -0.49).

CONCLUSIONS:

Our study provides a framework for providing information to patients with Duchenne muscular dystrophy and their families when introducing GC therapy. The study also highlights the importance of collecting longitudinal natural history data on patients treated according to standardised protocols, and clearly identifies the benefits and the side-effect profile of two treatment regimens, which will help with informed choices and implementation of targeted surveillance

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I'm interested in anyone's 'real-life' experience of the 10 days on/off regime versus daily? My just-turned-four year old son is due to start steroids in March and I'm extremely anxious that I'll make the wrong decision for him. We were edging towards the 10 on/off as he's already bothered by his short stature, is classed as 'doing well' and also as a mutation that will benefit from exon-skipping 51 (if approved, or if approved in time). We're thinking that a 'milder' regime might allow him to still grow a bit and maintain the quite good function he has, whilst he might possibly then also benefit later from Eteplirsen or Drisapersen? However, having now seen the results of this study, it seems there's a considerable difference in the length of time a boy is ambulatory. I hadn't realised that there would be such a discrepancy - 2.5 years is a long time to remain independent. I'd like to hear anyone's experiences if you don't mind sharing. Thanks.
I'd like to read the whole paper. Do you have the source?

J Neurol Neurosurg Psychiatry                                 doi:10.1136/jnnp-2012-303902                                

Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy

  1. 1.Valeria Ricotti1,
    2.Deborah A Ridout2,
    3.Elaine Scott3,
    4.Ros Quinlivan1,4,
    5.Stephanie A Robb1,
    6.Adnan Y Manzur1,
    7.Francesco Muntoni1,4,

       
  2. on behalf of the NorthStar Clinical Network
  • Published Online First 18 December 2012                                

First off - don't be anxious about making the "wrong" decision.  There's not right or wrong answer here, so don't be anxious about it.  Only you can decide what's the best decision for your son, given your personal situation.  I'll give you my opinion, though.

 

One thing to keep in mind about exon skipping drugs - or for that matter, most, of the therapies being explored right now.  They do not restore fibrotic muscle tissue.  Once muscle tissue is lost - it's gone forever.  If you're exon 51 skip eligible - I'd personally consider trying to maintain functional muscle for as long as possible, hoping that therapy will get approved before all muscle function is lost.  That 2.5 years of extended mobility you get under the daily regimen might make the difference.  It's a different situation, than say, you had a rare mutation, which even under the best scenario is probably many years from approval - if ever. 

 

Good luck. 

 

 

 

 



lisa burke said:

I'm interested in anyone's 'real-life' experience of the 10 days on/off regime versus daily? My just-turned-four year old son is due to start steroids in March and I'm extremely anxious that I'll make the wrong decision for him. We were edging towards the 10 on/off as he's already bothered by his short stature, is classed as 'doing well' and also as a mutation that will benefit from exon-skipping 51 (if approved, or if approved in time). We're thinking that a 'milder' regime might allow him to still grow a bit and maintain the quite good function he has, whilst he might possibly then also benefit later from Eteplirsen or Drisapersen? However, having now seen the results of this study, it seems there's a considerable difference in the length of time a boy is ambulatory. I hadn't realised that there would be such a discrepancy - 2.5 years is a long time to remain independent. I'd like to hear anyone's experiences if you don't mind sharing. Thanks.

Has anybody tried alternate use of prednisone and deflazacort? They have bit different side effects so the therapeutic effect might be as on daily regime and side effect as on intermittent regime.

I'm also interested in anyone's experience with weekend dosing.

Our son was on daily deflazacort for 9 years (from age 4 to 13).  In late October we switched from a daily dose to weekends only.   We switched because our son wanted to grow taller and we thought it would be a first step (growth hormones to be a second but that is another matter).  We have noticed changes in his facial features - less cushingoid and looking a bit older, more like a teen than a little boy.  Which is important at age 13.  He is ambulatory.  He has not grown yet, but it has only been a little over 2 months.  Our fear is that he will lose strength.  He is finding stairs much harder, almost impossible.  Is that the natural progression, or is it because we changed the dosing?  Hard to say because he was finding stairs harder before we made the change.  Further, the dose he is taking on the weekends is less than 1/2 of what he took when he took it daily.  His pediatrician has never given a weekend dose before and wasn't sure what dose to prescribe.  I think it is too low.  

I would love to hear from anyone on the weekend regime:

  • what dose is being given (mg/kg or just # pills and your son's weight);
  • if you noticed a change in ambulation;
  • if you notice fewer side effects (taller and less of a baby face);
  • any other information...

There is another study that states that the end results of weekend regime and daily regime are about the same, with fewer side effects with the weekend regime.  That said, I believe our son's dose is too low...

Angela

We switched our son to week end regimen,in last march,he was at daily dose of 18mg of Deflazacort/day,since last March he's on 30mg /day [sat-sun].almost 3 months later he grew almost an inch,he was very happy.Concerning his strength,I think he's still the same w/a little difficulties,w/stairs,also he's getting tired faster than before,but in general we're  happy over all.

Angela Bourgeois said:

I'm also interested in anyone's experience with weekend dosing.

Our son was on daily deflazacort for 9 years (from age 4 to 13).  In late October we switched from a daily dose to weekends only.   We switched because our son wanted to grow taller and we thought it would be a first step (growth hormones to be a second but that is another matter).  We have noticed changes in his facial features - less cushingoid and looking a bit older, more like a teen than a little boy.  Which is important at age 13.  He is ambulatory.  He has not grown yet, but it has only been a little over 2 months.  Our fear is that he will lose strength.  He is finding stairs much harder, almost impossible.  Is that the natural progression, or is it because we changed the dosing?  Hard to say because he was finding stairs harder before we made the change.  Further, the dose he is taking on the weekends is less than 1/2 of what he took when he took it daily.  His pediatrician has never given a weekend dose before and wasn't sure what dose to prescribe.  I think it is too low.  

I would love to hear from anyone on the weekend regime:

  • what dose is being given (mg/kg or just # pills and your son's weight);
  • if you noticed a change in ambulation;
  • if you notice fewer side effects (taller and less of a baby face);
  • any other information...

There is another study that states that the end results of weekend regime and daily regime are about the same, with fewer side effects with the weekend regime.  That said, I believe our son's dose is too low...

Angela

Thanks for the information. We see the neurologist this week. We'll see if he has grown. I think he has a bit. How old is your son?

Please look at our link www.miracleforthree.com for three kids with MD

Are you using the total dose for the week split by 2 days? Your doctor might want to read this article for dosing info: http://www.quest.mda.org/news/dmd-daily-weekly-prednisone-treatment...

Angela Bourgeois said:

I'm also interested in anyone's experience with weekend dosing.

Our son was on daily deflazacort for 9 years (from age 4 to 13).  In late October we switched from a daily dose to weekends only.   We switched because our son wanted to grow taller and we thought it would be a first step (growth hormones to be a second but that is another matter).  We have noticed changes in his facial features - less cushingoid and looking a bit older, more like a teen than a little boy.  Which is important at age 13.  He is ambulatory.  He has not grown yet, but it has only been a little over 2 months.  Our fear is that he will lose strength.  He is finding stairs much harder, almost impossible.  Is that the natural progression, or is it because we changed the dosing?  Hard to say because he was finding stairs harder before we made the change.  Further, the dose he is taking on the weekends is less than 1/2 of what he took when he took it daily.  His pediatrician has never given a weekend dose before and wasn't sure what dose to prescribe.  I think it is too low.  

I would love to hear from anyone on the weekend regime:

  • what dose is being given (mg/kg or just # pills and your son's weight);
  • if you noticed a change in ambulation;
  • if you notice fewer side effects (taller and less of a baby face);
  • any other information...

There is another study that states that the end results of weekend regime and daily regime are about the same, with fewer side effects with the weekend regime.  That said, I believe our son's dose is too low...

Angela

Thanks. I sent that article to our doctor.

This is what my Doc told me about regimes, and how to make intelligent decisions around choosing the most suitable one.

Body naturally produces cortizone and it typically takes about 15 days to detect a cycle change. So for a 10 day on 10 day off regime body reacts by producing less of cortizone, when extra cortizone given as a drug for 10 days. After this 10 day period the cortizone levels decline and it takes about 5 more days for the body to recognise that dosage from outside has stopped and it needs to produce more. Hence the total of 15 days for the body to adjust to a change in dosage. Till we are able to give these 2 weeks to a body to recognize changes, we should be fine.

In our case sometimes, specially during spring and autumn we were finding that my kid was developing some rashes on the skin during the 10 day off periods. These would disappear within a day or 2 of dosage start. Workign with our docs we then shift to 9 day on 9 day off regime specially during season change. Not sure how relevant is the season change for others.

Though managing tantrums is much easier with weekends, our doc suggested not to go for weekend. Her logic was that families tend to park most of the "To Dos "on weekends, and this gives the opportunity for the kids to burn themselves more with the mix of cortizone boost and lots of avenues to consume the burst. We choose not to go by weekend option, but then we did also not have major tantrum issues.

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