Tuesday, 17 September 2013

Clinic speak: how good are steroids for treating relapses?

Think twice before accepting steroid treatment for your relapse. #MSBlog #MSResearch #ClinicSpeak

"The study below mirrors my clinical experience that steroid treatment for relapses is unpredictable and at worst dangerous. Clinicians have a 'must  treat worldview' and have developed a culture that favors treatment over no treatment. When someone comes in with a relapse we tend to reach for the prescription pad and prescribe steroids. The data favoring steroid treatment of relapses is weak and if anything marginal. Firstly, the outcome at 6 months after a relapse is independent of whether, or not, you receive steroids. All that steroids do is speed up your rate of recovery from a relapse by about two weeks; in other words you get back to you old baseline, or new baseline, 2 weeks earlier if you have steroid treatment. Secondly, the evidence that steroids makes a difference when given 5 weeks after the onset of a relapse is non-existent; in other words if you are going to be treated with steroid you need to receive them as soon as possible after the onset of an attack. Thirdly, the dose counts; most studies of low dose oral have not shown a benefit. Therefore you need high intravenous or oral steroids. I would recommend the following protocols only: 
  1. 1g or 1,000mg methylprednisolone intravenously for 3 days
  2. 500mg methylprednisolone intravenously for 5 days
  3. 500mg methylprednisolone orally for 5 days
The oral methylprednisolone tablets are 100mg in size and not always available. When they are not available I simply instruct the pharmacist to dispense the liquid intravenous formulation that can be taken orally by being mixed with fruit juice. Please note that many pharmacists don't like doing the latter. 

Please note high-dosed pulsed steroids  have side effects. The following is a list of the more common ones:


  1. Increased appetite, weight gain
  2. Water retention with leg swelling or a swollen, "puffy" face
  3. Nervousness, restlessness
  4. Insomnia
  5. Sudden mood swings (happiness and sadness)
  6. Hypomania (persistent euphoria or extreme happiness) and rarely acute psychosis
  7. Avascular necrosis of the hip and other bones
  8. Thrombosus or clots
  9. Allergic reactions; this is not an allergic reaction to steroids, but to the incipients in the solution. If you are allergic to the IV formulation you can still take high-dose oral steroids.
With prolonged administration: 
  1. Muscle weakness
  2. Blurred vision
  3. Increased growth of body hair
  4. Easy bruising
  5. Lower resistance to infection
  6. Acne
  7. Osteoporosis (bone thinning)
  8. Diabetes or worsening of diabetes
  9. High blood pressure
  10. Stomach irritation
  11. Cataracts or glaucoma
As I have stated many  times before on this blog, avascular necrosis and psychosis are the side effects that worry me the most. As with all treatments there is a risk:benefit ratio and in my opinion  the risks of steroids outweigh the benefits for mild and sometimes moderate attacks. Obviously if your relapse is preventing you from functioning normally then speeding up the recovery is worthwhile. 

Some neurologists still use an oral taper; i.e. after the pulse of high-dose steroids is finished you go onto oral steroids that are then weaned over a 4-8 week period. There is no evidence that a taper makes any difference to the rate of recovery. I don't use it as it causes a large number of side effects. My only exception to this rule is rebound after the Lazarus effect. The Lazarus effect this is when MSers with a severe relapse, which renders them bed-bound, respond dramatically to a pulse of steroids; they literally get up and start walking 24-48 hours after starting steroids. If they then deteriorate after the pulse of steroids is finished and respond to a second course of steroids I will prescribe a taper to try and prevent a further deterioration. The latter presumably occurs from swelling of the a lesion in the spinal cord and a taper prevents this from reoccurring. Please note that since the wide-spread use of DMTs the number of  severe spinal relapses has plummeted and hence I have not seen a Lazarus effect in years. Since we have started using DMTs for treating RRMS not only has the number of relapses plummeted, but also the severity. Another reason for neurologists to use DMTs liberally. 

Another trend that has taken off in recent times is the use of monthly pulsed steroids as a DMT; typically 1g or 1,000 mg methylprednisolone intravenously monthly. In my opinion the evidence supporting this treatment is poor and hence I don't use it personally. The exception being is that if someone is referred to me on this treatment I tend to let them decide whether or not they want to continue, or not, with their monthly infusions after I have explained my position. In general, most MSers stop after hearing about the side effects. I have had one MSer referred to me with such bad osteoporosis from pulsed monthly steroids that she developed a spontaneous vertebral compression fracture. Hence the need to have a baseline bone density scan and to be put on osteoporosis prophylaxis if you are going to stay on steroids long-term."

The following is a short survey I would like you to complete on steroid use in MS:



Epub: Nickerson M, Marrie RA.The multiple sclerosis relapse experience: patient-reported outcomes from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. BMC Neurol. 2013 Sep;13(1):119.

BACKGROUND: Among MSers with relapsing-remitting multiple sclerosis, relapses are associated with increased disability and decreased quality of life. Relapses are commonly treated with corticosteroids or left untreated. They aimed to better understand MSer perceptions of the adequacy of corticosteroids in resolving relapse symptoms.

METHODS: They examined self-reported data from 4482 participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding evaluation, treatment, and recovery from relapses.

RESULTS: Forty percent (1775/4482) of respondents were simply observed for disease worsening, whereas 25% (1133/4482) were treated with intravenous methylprednisolone (IVMP) and 20% (923/4482) with oral corticosteroids; additional treatments included adrenocorticotropic hormone, plasmapheresis, intravenous immunoglobulin, and others. Among MSers who responded to questions about their most recent relapse, 32% (363/1123) of IVMP-treated and 34% (301/895) of oral corticosteroid-treated MSers indicated their symptoms were worse one month after treatment than pre-relapse, as did 39% (612/1574) of observation-only MSers; 30% (335/1122) of IVMP-treated MSers indicated their treatment made relapse symptoms worse (13% [145/1122]) or had no effect (17% [190/1122]), as did 38% (340/894) of oral corticosteroid-treated MSers (worse, 13% [116/894]; no effect, 25% [224/894]) and 76% (1162/1514) of observation-only MSers (worse, 17% [264/1514]; no change, 59% [898/1514]).

CONCLUSIONS: Overall, MSers with relapsing multiple sclerosis who receive treatment report better outcomes than those who are simply observed. However, a sizeable percentage of MSers feel that their symptoms following corticosteroid treatment are worse than pre-relapse symptoms and that treatment had no effect or worsened symptoms. MSer perceptions of relapse treatment deserve more attention, and more effective treatment options are needed.

Other posts on steroids:

13 Aug 2013
"In general I try and avoid high-dose steroids to treat acute relapses simply because of the potential complications. This case report is a reminder of one of the rare complications of this treatment; i.e. a clot in one of the venous ...
21 Mar 2013
"My first poster today at the AAN. The data speaks for itself. Treatment with BG12 reduces the need for steroids and hospitalizations. This data supports health economic arguments for BG12." ...
27 Jan 2013
METHOD: In a prospective study, we evaluated the MSers who received high-dose intravenous methylprednisolone for acute attacks. By repeated physical and laboratory examinations and history taking, MSers were ...
30 May 2013
#MSBlog #MSResearch. "My poster from the ISPOR 18th Annual International Meeting in New Orleans. The main finding is that BG12 or DMF reduces the proportion of relapses needing to be treated with intravenous steroids.

09 Nov 2011
Background and purpose: Temporary discontinuation of natalizumab/Tysabri is sometimes considered because of the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) ...
10 Jun 2012
Methods: Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age 45.2 yr) chronically treated with low-dose GC and in 54 healthy age-matched men.
25 Jul 2012
Epub: Rakusa et al. Testing for urinary tract colonisation before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation. Eur J Neurol. 2012. doi: ...
06 Feb 2012
Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with ...

04 Jan 2012
This is a report five MSers with femoral head necrosis who had RRMS and received different doses of methyl prednisolone. The cases consisted of 3 females and 2 males. The duration of disease varied between 1 and 3 ...

17 Dec 2012
Second-line treatments of steroid-unresponsive MS relapses and a possible algorithm for MS relapse management are also reviewed in this article. Whilst this is taking the coals to Newcastle if you are a RRMSer, some of the ...

21 Aug 2013
The other advantage of having less severe relapses for MSers is fewer course of high-dose steroids and hence less side effects and lower chances of those severe and unpredictable adverse events, for example avascular ...

14 comments:

  1. Interestingly a large review of steroids in the treatment of traumatic head injury indicated that steroids seem to make the situation worse and recommended that they should no longer be used.
    "The review authors searched themedical literature to determine how effective and safe corticosteroids are for treating brain injury. They
    focused their search on randomised controlled trials in which one group of people received a medical treatment (corticosteroids) and
    was compared with a similar group who received a different treatment or no treatment other than standard care. The review authors
    found 20 of these studies with 12,303 participants. When the review was first done the results of the research were inconclusive. A
    new large study with about 80% of the total participants was completed by the time of the 2006 update of this review. This study,
    called CRASH, showed a significant increase in number of deaths in patients given steroids compared with patients who received no
    treatment. The significant increase in deaths with steroids suggests that steroids should no longer be routinely used in people with
    traumatic head injury."

    ReplyDelete
  2. In some EU countries you're not eligible for getting DMT (not even 1st line) if you don't have 2 relapses treated with stereoids.

    ReplyDelete
  3. Some of the side effects can be reduced if you take some potassium pills (approx. 200mg/day). Especailly if you get the high doses.

    VitD3 & Calc. can limit the long time effects when it come to bone thinning.

    Thrombosis can be prevented by administering Enoxaparin sodium while on infusions. So can stomach problems by taking a Proton-pump inhibitor (e.g. Omeprazole)

    Potassium supplement is mainly a good descision if you get Methylprednisolon infusions as the have mineralcorticoid effects which can be prevented by taking pottassium compounds.

    If you get Prednisolon you normally don't need a pottassium compound as Prednisolon hasn't mineralcorticoid side effects.

    Simple, easy and cheap :)

    ReplyDelete
  4. Prof G - I recently was told by my eye doctor that high dosage of prednisolone is very advisable if one has optic neuritis because it's better for the eye recovery (as opposed to other symptoms) - is that true from your own observations in the clinic? I don't like steroids and if necessary take a very low dosis. Thanks.

    ReplyDelete
    Replies
    1. Anon 1:56 I had 1000mg Prednisolone intravenous for 3 days twice for optic neuritis. It worked very well both times. I could not believe I had no side effects. My Optic neuritis hasn't returned 18 years later. I had always refused steroids in the past.

      Delete
    2. I get 5 days with 2000mg of Methylprednisolon. Hasn't worked for my ON....
      AND I got the infusions in time.

      Some ppl seem to be unresponsive to steroids.

      Btw. are there any markers which can predict if someone is unresponsive?

      Delete
  5. It has happened a few times a relapse started and the neuro advised waiting it out. But the symptoms kept getting worse and the relapse kept getting longer. Finally steroids were given.

    I have never seen a proper full-blown relapse go away without steroids



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  6. Does steroids ultimately have any effect on the course of MS? Or on the level of the recovery from the relapse? Or is it only a shorter time of relapse to be suffered after cortcosteroid administration?

    ReplyDelete
    Replies
    1. There are no convincing trials that steroids affect the long-term outcome. One of the reasons is that no adequately powered or large enough studies have been done. The issue is really side effects; steroids longterm safety profile makes it an unappealing drug for treating MS.

      Delete
  7. "the evidence that steroids makes a difference when given 3 weeks after the onset of a relapse is non-existent" - A Cochrane Review by Filippini et al. (2000) concludes otherwise (please see Comparison 2 table) http://www.ncbi.nlm.nih.gov/pubmed/11034713
    Are there any studies supporting the quoted claim?

    ReplyDelete
  8. I think I only do well with low dose of steroids for short period with this I have improvement. Currently taking dose of dexamethasone, on 4th day of 5-6mg a day significantly worse. 1st 2 days saw improvement, then going in opposite direction.

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  9. Spot on with this write-up, I actually think this web site wants far more consideration. I’ll probably be again to learn far more, thanks for that info.

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    ReplyDelete
  10. lol my partner's old neuro prescribed steroids with a warning that they can cause heart burn (neuro was rather obsessed with heart burn lol)... my partner got really annoyed when instead of heartburn she didn't sleep for 3 nights in a row and had to beg her GP for sleeping pills.

    the neuro before the heart burn one prescribed steroids upon diagnosis as a way of testing whether she had RRMS (and got it wrong)

    you can imagine my partner's surprise, after all of this, when she actually sat down to read the side effects of high dose steroids herself instead of relying on neuros lol

    ReplyDelete

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