Nusrat et al. Anorectal Dysfunction in Multiple Sclerosis: A Systematic Review. ISRN Neurol. 2012;2012:376023. Epub 2012 Jul 29.
Background: Constipation and fecal incontinence are common in MSers. Despite their high prevalence and potential impact on overall quality of life, few studies have addressed anorectal dysfunction in MSers.
Aim: The goal of this work is to define the prevalence, pathophysiology, impact, and potential treatment of constipation and incontinence in MSers.
Methods: The PubMed database was searched for English language publications between January 1973 and December 2011. Articles were reviewed to assess the definition of the study population, duration, type and severity of MS, sex distribution, prevalence, impact, results of physiologic testing, and treatments.
Results: The reported prevalence of constipation and fecal incontinence ranged around 40%. Anorectal dysfunction significantly affected MSers with nearly 1 in 6 MSers limiting social activities or even quitting work due to symptoms. Caregivers listed toileting as a common and significant burden. The only randomized controlled trial showed a marginal improvement of constipation with abdominal massage. All other reports lacked control interventions and only demonstrated improvement in individuals with milder symptoms.
Conclusion: Anorectal dysfunction is a common manifestation in MS that significantly affects quality of life. Therapies are at best moderately effective and often cumbersome, highlighting the need for simple and more helpful interventions.
“Somebody was making the point in a comment yesterday that on average MS was not necessarily that bad and that in the modern era most MSers live with a good quality of life. This study demonstrates that if you look a little deeper than walking impairment, which is what the EDSS measures you find a lot of hidden disabilities that impact massively on QoL. Bowel and anorectal dysfunction is one of these.”
“Does the person who made that post yesterday know how embarrassing and socially isolating bowel dysfunction is for MSers? I look after several MSers who have become recluses because of this problem. Again it is better to prevent this problem than treat the consequences.”
“Anybody share my perspective?”
That comment (not posted by me) was in response to Iain O, who seems to be a newly diagnosed RRMSer unduly pessimistic about his prospects. Do you agree with him that even new MSers will miss the bus for early aggressive treatment?
Re: "Do you agree with him that even new MSers will miss the bus for early aggressive treatment?"Only if they see a neurologist who is a therapeutic nihilist. Most will try and ascertain who has active MS and who has poor prognostic features before deciding on a therapeutic strategy. The worst crime is to tell someone up front they have benign disease and to then not monitor them. MSers with a good early prognostic profile may do very badly; it is getting the timing right with regard to treatment.
Prof G – It was I who made the post to which you refer above. I think your implicit criticism is unfair and perhaps based on a misunderstanding of my post. I was not minimising the many awful and varied symptoms of this terrible disease. It was, as the above post mentions, in response to a post by Iain that said/implied "everyone I know with MS has contemplated suicide" and "I'm not willing to live a life with someone cleaning up after me when I go to the toilet". A newly diagnosed MSer reading that could be forgiven for thinking that quadraplegia and full-time care was an inevitable outcome of their disease. It is not. Many people with MS live fulfilling and happy lives in spite of the challenges MS may present them; look at the MS paralympians or people like Mark Lewis (the phone tapping scandal lawyer) or Ann Romney (who may soon by the First Lady of the USA) – these people are not sat waiting to die, having their bums wiped as Iain put it. Many people with MS will not consider suicide even for a second. Many people with MS will have a relatively mild disease course (hence your post above about identifying people with good early prognostic profiles and monitoring to ensure that remains the case). The EDSS is walking-biased but does actually account for disability in all functional systems including anorectal (it is fatigue/cognitive functioning that it fails to take account of). New disease treatments – with great people like yourself looking for more effective ones all the time with admirable commitment and determination – means that newly diagnosed people can look at their future with at least a degree of optimism and not simply prepare to move into a nursing home. If that weren't the case then we'd surely treat everyone with the strongest drugs possibe the second they were diagnosed, regardless of risk profile. Surely that MS can be mild and/or well-managed and not always ruin lives as contemplated by Iain isn't a controversial proposition?
Just to divert back to the original topic, though I find the discussion very interesting. Prof G,I wonder what effect some of the drugs comonly taken by MSers have on digestion, eg Baclofen, Tizanidine, and whether they slow down the action of peristalsis because the muscles are relaxed? What I mean is, are MSers having anorectal problems because of treatments, rather than the underlying MS?Thanks
"Does the person who made that post yesterday know how embarrassing and socially isolating bowel dysfunction is for MSers? I look after several MSers who have become recluses because of this problem. Again it is better to prevent this problem than treat the consequences.""Anybody share my perspective?"G: are you doing politics now? what's the point of this comment? it's an insult to my MS. Do you know what the readership of this blog is ? or is just cheap populism?You can do better….
I always wondered whether my Irritable bowel syndrome had anything to do with my MS!After all, they are both wrongdoings of the immune system from what I understand.
Dear TonyYou apear to be one of the MSers ho have other autoimmune diseases. The differences in autoimmunity is often at the the level of the target, which may mean you have avariant of a transplantation molecule (HLA) that predisposes you to more than one autoimmune condition but it is likely that there are shared pathways in both diseases. As such it is not unknown that one immune inhibitor will work in more than one immune-mediated condition eg. tysabri.
Re: "MSers having anorectal problems because of treatments, rather than the underlying MS?"Treatments can make constipation worse, they don't cause incontinence. The latter is usually due to spinal cord disease.
Re: "are you doing politics now?"No. It only takes one strategic spinal cord MS lesion to leave you with anorectal dysfunction. If the spinal cord does not recover the dysfunction is permanent. The point I am trying to make is that it is better to prevent this happening if you can. You can't predict, with any accuracy, where MS will hit next or how severe or benign your disease will be. Benign MS is a retrospective diagnosis; you have to have the disease for at least 15 years with no disability before you can be labelled as having benign disease. In hospital populations of MSers about 30% have benign disease at 15 years, which drops to 15% at 25 years. In community based populations this figure is ~45% at 15 years. All these data are based on the EDSS that does not capture hidden symptoms very well, for example depression, anxiety, cognitive impairment, sphincter dysfunction, etc. We have to be very careful what we label as benign MS.
In which case, shouldn't everyone be offered the most aggressive treatments possible, including Alemtuzumab when it resurfaces? Shouldn't I be able to balance the risk of side effects eg PML/ITP depending on the drug (typically at 0.1-1%) against risk, for example, of anorectal problems (apparently 40%). I know how I would play those odds…
My son (early 20's) has relatively early MS. He was relapsing on rebif and began to suffer faecal incontinence during relapses. He was in tears with the shame and embarrassment of it. He's had alemtuzumab off licence. No relapses since and no more faecal incontinence. Thank God his spinal cord lesion was not so damaged that it couldn't repair itself
Is you son otherwise well? Any negative effects from the Alemtuzumab? Does he have any residual disability from the relapses or is he (at present at least) 'cured'?
Re: "In which case, shouldn't everyone be offered the most aggressive treatments possible, including Alemtuzumab when it resurfaces? Shouldn't I be able to balance the risk of side effects eg PML/ITP depending on the drug (typically at 0.1-1%) against risk, for example, of anorectal problems (apparently 40%). I know how I would play those odds…"Alemtuzumab will only be licensed for MSers with active relapsing disease and may the EMA or NICE will narrow that group down further. Alemtuzumab is a risky therapy not everybody is prepared to take risks. We need to respect this. I have a few MSers who don't want DMTs at all; this is despite being eligible for treatment under the ABN guidelines.
Alemtuzumab will only be licensed for MSers with active relapsing diseaseIsn't that – by definition – everyone newly diagnosed (assuming that to be diagnosed they need to have had a relapse and/or sub-clinical activity and disemmination in space and time)?Also, respecting patient choice on risk is one thing. Allowing EMA/NICE/risk averse neuros to take that choice out of their hands is surely another?
My son (off licence alamtuzumab) is fine. He has monthly blood tests and is aware of the need to watch out for unexplained bruising. He is not back to normal- his balance is still affected as is his bladder, but he has stabilised. When on a relapse he could hardly walk a mile (early MS- I know lots of MSers would love to be able to walk that far) but since alemtuzumab he's walked 11 miles in one go.
That's great news. I hope he stays relapse free and also doesn't progress to SPMS (one potential yet still to be seen benefit of Alemtuzumab early in disease course). Has he had MRI monitoring? Has he stayed free of new lesions as well as clinically stable do you know? How long ago did he take Alemtuzumab? Has he had second dose yet? (sorry for all the questions – it's just very interesting to talk to someone with direct patient experience of Alem). Was he ill from the infusions at all?
He only had the 2nd alemtuzumab 6 months ago. You get IV steroids before it to help with any side effects during the infusion. He needed IV anti sickness and ordinary paracetemol during the infusions. He also got the 'campath rash' that came and went for a few days post infusion. No problems otherwise- but he was careful about what he ate for 3 months post infusion.He is being monitored MRI- the last one said no new lesions, but it is early days, let's see what the months and years ahead bring- hopefully neuroprotective agents.
Well, I wish him the very best and hope he continues to improve or, at least, remain stable.
Re: "Isn't that – by definition – everyone newly diagnosed (assuming that to be diagnosed they need to have had a relapse and/or sub-clinical activity and disemmination in space and time)?"The licensing of the drug is usually bsaed on the inclusion criteria of the clinical trials; i.e:CAREMS-11. Diagnosis of MS and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years2. Onset of MS symptoms within 5 years3. EDSS score 0.0 to 3.04. ≥2 MS attacks within 24 months, with ≥1 attack within 12 monthsCAREMS-21. Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS2. Onset of MS symptoms within 10 years3. EDSS score 0.0 to 5.04. ≥2 MS attacks within 24 months, with ≥1 attack within 12 months5. ≥1 MS attack (relapse)during treatment with a beta interferon therapy or 6. glatiramer acetate after having been on that therapy for at least 6 months within 10 yearsSo you have to have more than 1 attack and have early disease. There are no guarantees that alemtuzumab is going to widely accessible to MSers.
It would be a real disgrace is such a promising treatment were restricted to those who were treatment non-responsive to GA or IFN. Not having an obvious relapse whilst on GA does not mean GA is halting the progression of your MS. Does 'attack' in the definition above include sub-clinical progression?
This is, sad to say, the real state of affairs. If GA stops you relapsing it's likely that you'll be kept on it. Even if your neurons are being timed to self destruct 10 years down the line.People with HIV get access to drugs even when their disease burden is minimal.But I feel that the MS community isn't loud or visible enough to demand its rights more.And, of course, we are all susceptible to the profit driven motives (this isn't a judgement call – it's just a statement of fact) and the other marketing machinations of the drugs industry.Imagine a scene in the early 1990s in New York. Imagine a major drug company pulling a drug that has been shown to be efficacious in HIV and putting it on hold for (what 2 years) a time… the invigorated, angry, political, outrageous and eloquent gay community would not stand for it. There would be demonstrations, headline news, killer heels…But Campath slips from our grasp – with the prospect of a £66,000 price tag on a relabelled (they call it new!) drug coming down the pipeline. Do we scream? Do we urge India to get on the generic bandwagon? Do we lobby, protest, counter, argue, defend and take to the streets?No. We don't even burp in protest.MSers won't end with a bang. We won't even manage a whimper.Well. I'll be vocal. One day soon I'll come out of the MS closet and use what little clout I have in the media to get things shaken up a bit. I'm just working out how best to do this.I am beginning to find my MS voice. And it's an angry one. Not just for me. But for all of those who have lost, forgotten or just never found theirs.The nice thing is I think Prof G agrees with this in a quiet way. And Mouse Doc probably does too.(Maybe not the HIV / Pharma analogy, but at least the sentiment of MSers taking some political action).
There are two, related but distinct issues. One – licensing and two – NICE/NHS/PCT. in respect of licensing, there should be no issue. If someone with MS wants and, NHS aside, can afford Alemtuzumab they should be allowed to take that decision. To limit patient choice would be appalling, paternalistic nonsense. In terms of NICE etc I think we have to be realistic – they have limited funds and will want to manage people in the cheapest way possible. Even if NICE are relatively flexible, local PCTs can ignore and refuse to pay. The big hope with Alemtuzumab is, actually, it is cheaper as it is usually only a two dose deal. £60k for two doses a year apart is cheaper than GA at £6,000 pa for 20 years. I'm sure Genzyme will make that point. The counter is that NICE are very short term focused (who knows what the budget will be next year etc) and so whilst Alem might make long term economic sense, it might still be highly restricted. Me? I'm saving up and I'll be taking Lemtrada as soon as the EMA or FDA approve it, even if I have to travel to Eastern Europe to find a neuro who'll prescribe it to me – sod the NHS. £60k is nothing in the context of the potential to 'cure' my MS.
I'm not sure, but once it's approved by the EMA/FDA I would've thought any neurologist working privately would be able to prescribe it- if you're willing to pay, without the need to go to Eastern Europe. Also I think ProF G mentioned some time ago that it's difficult to copy alemtuzumab as its a monoclonal antibody, not a drug,so I'd be very wary of anything purporting to be 'like alemtuzumab' from India or elsewhere.
This might be the case, but it looks like Sanofi is going to up its price from £10k to £60k. This will likely mean that only those with either a big cheque book (to go private) or clear disability progression on First Tier DMTs (and so even if it works, likelihood is you'll still have disability) will get it.What hasn't been made clear is this: by taking Campath off the market, does Sanofi retain intellectual rights to the creation of monoclonal antibody production? Does it mean that the new drug they will launch in its place will start the IP ownership of such a drug from year 0? I imagine so.This strikes me as abusing the system of IP ownership. Withdrawing a drug and then relaunching the same drug as another name but at 6 times the price with the clock going back to 0 on IP rights… surely this should be challenged? But by whom? I don't buy into the argument that to interfere in this case would harm R&D in Pharma.Coles in Cambridge was innovative to work out that Alem might work in PsMS. Yes, he got funding… but the risk to Sanofi wasn't from ground zero. They had already got the drug in their armoury.What is the main issue here? This: that the most efficacious drug on the scene for MS at this moment in time has just been taken out of reach of the majority of people with MS. So people will accrue disability where they need not. Jobs will be lost by people whose disability increases where jobs need not be lost. QOL will be diminished. All due to a £50k add-on pricing strategy.And as for the 'poll' that Prof G has very sensibly done on this matter? I am very concerned that the PR company that Sanofi has hired to manage their reputation might be voting on it. I know that they are monitoring social media on this story.
Yes there are no copies of CAMPATH-1H so avoid anything proporting to be a me-too. If it were a drug then we would not even be talking about it as it has taken too long to get to Market, it is well over twenty years old and the original patent would be long expired.
If the PR company is voting on the poll about Alemtuzumab being withdrawn, it will not matter much because it has been withdrawn, whether we agree or not. If it comes out that the majority agree I would be very surprised but you have probably just given the PR company marketeering Lemtrada an idea. We are aware that companies may use anon or otherwise posting as marketeering opportunities, e.g. sometimes we hear about adverse events of some drug very quickly.Whilst repackaging may speak to safety monitoring at the center of Lemtrada it is just plain Alemtuzumab dressed up in new packaging in a new vial size with probably a vastly higher price. However this was always going to happen otherwise Sanaofi/Genzymne would not have paid for the trials and the rest. The question is how much increase is this going to be? Maybe this is why Sanofi bought GenzymneWith regard patents, I doubt there is little to stop another company making a new antibody against the same target i.e. CD52 but they would have to do the same trials that alemtuzumab has done and ensure that existing patents are not infringed. Companies layer as many patents around their drug as possible to make it as unappeallng as possible for others to follow in the footsteps.Also any me-toos would be years behind Sanofi/Genzymne unless a sting in the tail occurs. However these companies have legal teams working out how to extend the life of patent protection.Glaterimer actetate patents expire I think in 2014 but this agent was made in the 1970s A dosage and timing of delivery patents of CAMPATH-1 in MS was filed by Genzymne and this creates new patents such as WO 2008/031626 filed 2006. Who knows there may be fillings on once a week delivery rather than infusion over 5 days or maybe subcutaneous formulation. When companies make drugs they have a stable and as one comes to the end of its patent life a newer better version replaces it.Maybe one should be asking why Cambridge University did not do these studies through government, rather than company support many years ago. Coles got funding but from Companies Genzymne had to pay for others work when they bought the licence so they did not buy it from time zero but if you buy further down the line it costs a load more. They crated their own monster by licensing to pharma, however I am sure the University of Cambridge are saying thanks very much for the wads of cash they will get. However thats what Governments wants…academic entrapeneurs
Surely the marketeers from other companies could also try fixing the vote the other way round. There aremore antis than pro compnaies?