This Is MS Multiple Sclerosis Community: Knowledge & Support

Just had an evaluation by a new neuro and he dx'd me as SPMS I think based on the length of time I seem to have had the disease. I never seemed to have had an RR form of the disease. I had a bout of ON in 1985 that eventually resolved and have not had a recurrence of that. The results of the LP at that time had some very strong indicators of MS ( 5 O bands, elevated MBP and elevated IgG). I was going along fine untill about 6 years ago when I begin to experience neuropathic pain in my lower legs and that has continued to be my complaint along with worsening balance.

His recommendation was IV Solumedrol (he was ready to give an IV in the office that day), MRI and evoked potential test, and to consider Betaseron. I told him I would have to think about it and get back with him. When I questioned the effectiveness of CRABs for SPMS and told him that I had read that they were only about 30% effective and were not considered to be even that effective for SPMS, he asked where I was getting my information. I did not respond to that question. He also went on to say that he sees research data all the time that shows that the CRABs are about 50% effective. My questions to those that frequent this site are 1) are CRABs considered an effective tx for SPMS and 2) if so, where can I find the data that supports that argument. If not, where can I find the data that shows that CRABs are not effective for SPMS. At this juncture in the road I am thinking about giving the abx a trial before I go the CRAB route.

I was also given a packet of information (put out by the makers of Betaseron) to help me make an informed decision. Where are all the users of the CRABs that are happy with them (side effects and all). I do check their forums from time to time and it is kind of a mixed review. I don't know if the argument of "it's the best we have to treat MS right now" is good enough for me because I feel that it plays on the patient's fears of doing nothing and continuing to progress. I know several MS patients personally that seemed to have continued to progress while taking a CRAB and one friend has tried a couple of different ones and has not been happy with them. The last one she tried was Betaseron and she was not happy with it. I do want to make an informed decision, but I want idependent data and patient testimonials negative and positive). Also it seems that doctors are so quick to recommend a CRAB at the first sign of MS. Could it be the case that some of these patients may not have MS at all therefore the data supporting the use of a CRAB could posibly be skewed. I do believe I have read that having lesions does not necessarily correspond to disability level. Does relapse rate correspond to lesion load? So what if by being on a CRAB one does not have the formation of new lesions but continues to progress in disability. To me something is wrong with tht picture ( I guess you might consider that a pun) The treatment (until a cure is found) should be one that improves disability level and makes a patient feel better. I suppose that may be a novel idea.

I don't deny that I have MSand I don't deny that I am probably SPMS, I just did not think I was quite as "bad off" as the neuro seemed to think I was. Sure my balance has become worse and I may not have the stamina that I once had, but I'm still ambulatory without assistance, still do all my own husework, still exercise some and try to take care of myself, so I was a little surprised at the "worse case scenario" assesment.

Throwing in an interesting tidbit about the neuropathic pain - a serendipitous discovery . The night I forgot to take the 10 mg of Baclofen at bedtime, the better I felt the next day. So I have tried leaving it off several nights in a row with similar results. A little T&E I don't think I will continue with the baclofen.

Any info or comments would be greatly appreciated.

Ladelle

Here's a bit of information from Pubmed on Betaferon for SPMS:



Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study.

Neurology. 2004 Nov 23;63(10):1788-95.
Panitch H, Miller A, Paty D, Weinshenker B; North American Study Group on Interferon beta-1b in Secondary Progressive MS.
University of Vermont, College of Medicine, Burlington 05401, USA. hillel.panitch@vtmednet.org

OBJECTIVE: To evaluate the efficacy and safety of interferon beta-1b (IFNbeta-1b) in subjects with secondary progressive multiple sclerosis (SPMS).

METHODS: This 3-year, multicenter, double-blind, placebo-controlled, randomized trial of IFNbeta-1b included 939 subjects from the United States and Canada with SPMS and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were randomly assigned to receive either placebo or IFNbeta-1b (250 microg or 160 microg/m2 body surface area), administered subcutaneously every other day. The primary outcome was time to progression by > or =1.0 EDSS point (0.5 point if EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes included mean change in EDSS score from baseline, relapse-related measures, MRI activity, and a standardized neuropsychological function test.

RESULTS: There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNbeta-1b treatment groups. However, IFNbeta-1b treatment resulted in improvement on secondary outcome measures involving clinical relapses, newly active MRI lesions, and accumulated burden of disease on T2-weighted MRI. Effects were similar for both IFNbeta-1b treatment groups. Neutralizing antibodies to IFNbeta-1b were detected in 23% of 250-microg and 32% of 160-microg/m2 recipients, but their presence did not consistently affect clinical or MRI outcomes. IFNbeta-1b was also well tolerated at both doses.

CONCLUSIONS: Although no treatment benefit was seen on the time to confirmed progression of disability, relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested, a result consistent with the outcomes of earlier clinical trials.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum



Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials.

Neurology. 2004 Nov 23;63(10):1779-87.
Kappos L, Weinshenker B, Pozzilli C, Thompson AJ, Dahlke F, Beckmann K, Polman C, McFarland H; European (EU-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board; North American (NA-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board.
Outpatient Clinic Neurology-Neurosurgery, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. lkappos@uhbs.ch

BACKGROUND: A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS) showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset.

METHODS: Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables.

RESULTS: The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found.

CONCLUSIONS: Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum



Spotlight on Interferon-beta-1b in relapsing-remitting and secondary progressive multiple sclerosis.

BioDrugs. 2004;18(5):343-7.
McCormack PL, Scott LJ.
Adis International Inc., Yardley, Pennsylvania 19067, USA. demail@adis.co.nz

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomized, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalizations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomized trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity.

In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomized, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria.

In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum



Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study.

J Neurol. 2002 Aug;249(8):1058-62.
Fernandez O, Guerrero M, Mayorga C, Munoz L, Lean A, Luque G, Hervas M, Fernandez V, Capdevila A, de Ramon E.
Servicio de Neurologia, Complejo Hospitalario Carlos Haya Avda, Carlos Haya, 29010 Malaga, Spain. ofernand@hch.sas.cica.es

Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone.

Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured.

Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients.

Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months ( p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum

Ladelle,

As you are discovering, the decision on whether to take one of the CRABs, especially for SPMS, is a difficult one. Like most medications for MS, trying to find one that will work best for you can become a real challenge. The results that MS patients get from these medications are all over the map.

Generally speaking, the CRABs help about 1/3 of the patients that use them and that "help" is usually limited. I don't know where your neuro gets that the CRABs are 50% effective because they are not considered anywhere near that level. Up until about two years ago, none of the CRABs were used for SPMS but the makers of Betaseron supposedly revisited their data on earlier trials and came up with the result that Betaseron could be used for this. I don't know how they came to that conclusion but that is what they advertise now.

Now that Tysabri has been re-approved, you often hear neuros stating that they are glad to have an alternative to the CRABs because of their limited efficacy and numerous side-effects. Interesting to hear how the view about the CRABs can change at a moment's notice.

Some SPMS users have chosen to use LDN (now dose naltrexone). In pill form and very inexpensive, there is a ton of anecdotal evidence out there that the users say that LDN stops progression of their MS. While no clinical trials have ever been done to prove this, there is far too many MS patients who have been helped by LDN to make it not worth considering. At the same time, don't expect your neuro to consider LDN for one second.....most do not because of the lack of clinical trial evidence.

Whatever your decision, I hope it works out for you.

Harry

In response to dignan's post which mentioned combination therapy of an interferon and azathioprine, I strongly caution AGAINST azathioprine (Imuran). There is great suspicion that it causes cancer. (I think it was in The Autoimmune Connection by Baron-Faust and Buyon that it was mentioned 3 times.)

I had a dear friend, who had myasthenia gravis (MG), another "autoimmune" disease. who took Imuran, and who developed inoperable liver cancer. She died 6 years ago.

Hi Coach,

I appreciate your dilemma. I have had PPMS/SPMS? for too long, also. The problem is that you won't find sufficient hard-core evidence on any treatment; be it CRAB's, LDN, ABX, Aimspro, BVT etc. etc.

Just my opinion but 'suck it and see' is my motto. Try everything. What doesn't work for someone else, may work for you.

From my observations, of those who have done the CRAB's, Copaxone seems to get the 'thumbs up' over other CRAB's and I think some are doing it with other treatments, including ABX. What would your doctor think about Copaxone?

Regards,
Phil.

You know, it's a hard toss-up for a neuro with regard to how to present MS, especially SPMS, to a patient. If you don't stress its importance enough to some patients, they won't take their disease seriously. Then again, if you tell them about SPMS and what the real state of their disease is too strongly, you might make it worse for them.

I would think it goes like this: If you have a patient who appears just a little too "up-beat" about their disease and appears to be in psychological denial (either because they've been lucky so far, or they just don't want to face what WILL happen in the near future - IF you have a progressive form of MS), then as a physician, in order to be certain they understand the seriousness of them considering treatment, you may end up coming across very strongly to them and may sound "doom and gloom".

Now............If you have a patient who is freaking out TOO much over having SPMS, a doctor would most likely have to "downplay" the seriousness of the disease in order to get the patient into a psychological state where they can make judgment calls about their treatment more rationally.

I have a co-worker who was just diagnosed with RRMS, and since she has been lucky so far, she doesn't want to admit she has MS at all. I find myself wanting to SCREAM at her that she needs to take her diagnosis at least a little more seriously! On the other side, if she were freaking out about the diagnosis, I'd be reassuring her that it might not end up being as bad as she fears. Depends on the psychological state of the patient.

I'd have to agree almost TOTALLY with Brainteaser, IF you have been diagnosed with one of the progressive forms of MS. It is known what WILL happen with the progression of those forms of the disease. As long as you stay in the RRMS stage, anything might or might NOT happen. BUT, once you hit the definite progressive types of MS, you KNOW you will continue to progress, so treatment is of much larger concern.

Phil, to my knowledge, Copaxone doesn't show ANY applicability for SPMS treatment, so I doubt that trying that for SPMS would be useful. And I would doubt you could get a neuro here in the U.S. to prescribe Copaxone for SPMS.

About the only thing with any real "recognized" numbers associated with it for treatment of SPMS (and that have clinical trial results) is the CRAB Betaseron. Harry is right, though, as far as the CRABs go in general; but right now there isn't anything much else that a neuro can suggest, and have ANY legitimized legal justification for.

Oh, and Ladelle? The neuro you saw has about 600 MS patients alone (to my knowledge anyway), and perhaps with his experience in prescribing Betaseron to his SPMS patients (which I know he has been doing for a long time now), he may indeed have noticed closer to a 50% efficacy rate.

It all sucks, though, doesn't it?

Deb

Ok.....here we go.

Ladelle: My gut feeling was that the neuro you saw came back from the Greece conference that he went to recently with some new statistical "figures", but before I said anything for certain, I wanted to see what was presented in Greece.

As a general rule of thumb now, it appears that Betaseron for treatment of MS (not necessarily specifically for SPMS, though) is now being shown at about a 50% efficacy rate.



I know, I know............those are the statistics that the pharmas come out with, but for right now, since pharmas are about the only ones who can afford conducting the majority of clinical trials, the data that the neuros have no real choice but to "rely" on (for lack of a better word) are the pharma trials.



So, anyway, that neuro didn't lie. The stats he is seeing DO say 50%.

Deb

Hi Deb,

Good to hear from you.

You and Harry are no doubt technically correct about Betaseron being the only 'legitimate' CRAB for SPMS and partly, this is the reason I raised Copaxone. In Australia, my neuro had me on Copaxone with and without Imuran for as long as I wanted it which turned out to be about 2 years, finishing 2 years ago. I found it easier to cope with than an earlier period of Betaseron although neither seemed to help me. Nonetheless, it was a useful exercise and I then moved on to other treatments. Importantly, despite the progressive nature of my MS, I appreciated my neuro at least trying different treatments for me. I believe the approval criteria in Australia is similar to the US & Canada.

Regards,
Phil.

Ladelle

In the UK Betaseron (Betaferon as it is known here) is currently the only CRAB approved for SPMS. And I must say that was a factor that weighed with me when deciding which regime to start.

My personal experience of its use has been very unremarkable. Using the sprung-loaded gadget they provide the jab itself I find not pleasant but not painful. And fortunately, after about 9 months use, I've not had any bad site reactions. Mixing the product is a bit of a bother but nothing serious if you can use both hands. Set against this you dont need to keep the product in a fridge, this makes travel easy too.

Good luck with whatever choice you make.

_________________
John
I am what I am

Hi, Phil! Good to see you, too!

Yes, I agree with you about your neuro and trying different things. That was the way I was when it was THOUGHT I had definite MS. I was also prescribed the medications (even though way out of the box) that I chose for my "MS", even though they were very untraditional to say the least (after I considered and then refused taking any of the CRABs). Whether it turned out in the end that I had/have MS or not, I do appreciate now my first neuro's willingness to let me give those meds a chance (when it was thought we were treating MS), ya know?

And who yet knows about me for sure? A few weeks ago, I had three toes on my right foot suddenly go completely numb and stay that way for weeks! (Numbness like that is not part of fibro.) That was a new one for me, and kinda scary. I even picked myself with a pin and couldn't feel a thing in my toes! After about three months or so, though, I see that feeling is starting to return. So, who knows what really is going on with me. We may never know it all.

And I hope you are doing well, by the way, Phil!! Keep up the good fight!

Deb

Ladelle,

Making a decision as to whether to try one of the CRABs or not is excrutiating to make. I know - we all know.


I battled with myself about it for weeks, then decided I would try one, then backed out of it and said no, I wanted to try something else first. I'm just SO thankful that the "something else" appears to be working for me..............whether it is MS, fibro or Debitis!


Deb