New prescribing guidelines for multiple sclerosis

Scolding N et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis Pract Neurol 2015

The Association of British Neurologists (ABN) revised prescribing guidelines for the treatment of relapsing-remitting MS (RRMS) have been published. MS charities had the opportunity to comment on the revisions and contribute the patient voice.

In the last 20 years the UK has gone from having no available treatments for RRMS to having eleven. 

The whole document can be read online but here are some extracts:

In June 1999, the ABN first published guidelines for the use of the licensed MS DMT. This 2015 revised guideline replaces former versions. It includes all newly approved or licensed treatments for MS and represents a consensus concerning their use. These guidelines will require future revision as other treatments receive approval (eg, daclizumab and ocrelizumab).

The guideline is not intended to provide a complete description of the possible complications and monitoring of disease-modifying treatments in MS.
  • In the individual patient, MS remains a fundamentally unpredictable condition. 
  • We stress the importance of shared conversations about disease activity, risk and benefit, to make the choice that is right for the individual and their circumstances.
  • The ABN believes that people with MS should be managed by neurologists with specialist experience.
  • All of the licensed disease-modifying treatments for MS – β-interferons, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, natalizumab and alemtuzumab – reduce relapse rate and MRI lesion load. 
  • We suggest that these seven agents can be divided into two broad classesdrugs of moderate efficacy (average relapse reduction in 30–50% range), including the β-interferons, glatiramer, teriflunomide, dimethyl fumarate and fingolimod; and drugs of high efficacy (average relapse reduction substantially more than 50%), alemtuzumab and natalizumab. Side effect profiles vary considerably between
  • the Mitoxantrone has significant adverse effects and is not obviously superior in efficacy to the newer drugs of high efficacy. It is not licensed for MS in the UK, but is still used
  • There is a consensus that none of the currently available disease-modifying therapies significantly modifies progressively increasing disability that is unrelated to relapses (progressive non-relapsing MS).The implication, however, is that no disease-modifying treatment is effective, or indicated, in patients with established progressive MS in the absence of relapses.
  • It is not yet clear whether treatment should aim for a target such as ‘no evidence of disease activity’—either clinical or radiological. 
  • New MRI lesions are a more sensitive index of inflammatory disease activity than clinical relapses, occurring up to 10 times more frequently than clinically eloquent relapses.
  •  Many now substitute MRI activity for clinical activity in the classification, diagnosis and management of MS. 
  • Recently, the European Medicines Agency has explicitly recognised that MS may be defined as ‘active’ on radiological or clinical evidence.
  • Meanwhile, particularly in the first years after diagnosis, it is appropriate to consider including MRI scanning during the annual review recommended by the 2014 NICE Clinical Guideline for the management of MS, both on grounds of monitoring efficacy and safety. 
  • There are now many people with relatively long-standing relapsing–remitting MS who have used β-interferons or glatiramer for perhaps several years and whose disease is stable clinically. It is unclear whether such patients would benefit from MRI monitoring.
  • Immunotherapies appear particularly helpful when given early to people with active relapsing–remitting disease, before there is fixed disability or secondary progression. 
  • MS specialist neurologists may adopt either an ‘escalation’ strategy or an ‘induction’ strategy in treating MS. The ‘escalation’ strategy involves starting with the drug that is considered the least toxic but which will control the patient’s disease, and escalating to more potent therapies in the face of continued disease activity. An ‘induction’ strategy involves giving a powerful drug, with significant side effects, early in the disease.
  • As newer treatments emerge and when there is clinical equipoise agreed between clinician and patient, and there are clinical trials available for recruitment, then patients should be offered participation in relevant studies.
  • UK health systems have diverged with the devolved administrations in respect of treatment guidelines and/or restrictions. 
  • These differences render it now impossible to make treatment recommendations that are simultaneously compliant with all of the relevant advisory or statutory medicines agencies.
  • The ABN continues to support a fundamental principle of the NHS that, despite these changes, all patients have a right to access the appropriate expertise and therapy.

General management advice

  • It is important that patients and neurologists fully appreciate the risk and benefit of drugs, and of leaving the disease untreated. 
  • Patients should also discuss the risk as well as expected benefit of treatment; monitoring requirements; and work, family and other factors that are personally important, and clinicians should take account of their views in making the treatment selection.
  • MS specialist nurses play a key role in supporting patients 
  • Patients can also obtain information from patient groups, particularly the Multiple Sclerosis Trust and the Multiple Sclerosis Society, which have produced information leaflets in plain language, as well as a range of leaflets on other symptomatic, psychological and social aspects of living with MS. There are also several excellent websites particularly targeted towards patients, providing valuable information and guidance.
  • Once started on therapy, continued supervision by the specialist MS team is essential to identify side effects and assess therapeutic efficacy.

Recommendations for starting disease-modifying treatment
Eligible patients will normally be ambulant (maximum EDSS 6.5). There are no treatments licensed for use during pregnancy (but see below).

As mentioned above, the currently licensed disease-modifying treatments divide broadly into two classes:

Drugs of moderate efficacy (‘Category 1’)

  • β-interferons (including ‘pegylated’ β-interferon)
  • glatiramer acetate
  • teriflunomide
  • dimethyl fumarate
  • fingolimod

Drugs of high efficacy (‘Category 2’)

  • alemtuzumab
  • natalizumab

Relapsing–remitting MS
Patients with relapsing–remitting MS who have had two or more clinical relapses in the previous two years are considered to have ‘active’ disease that warrants consideration of disease-modifying treatments. T
he European Medicines Agency has explicitly recognised that disease activity may be established on radiological or clinical grounds.

All individuals with active relapsing–remitting MS should be considered expeditiously for treatment. 
Most are likely to start treatment with a Category 1 drug. 
  • Dimethyl-fumarate and fingolimod are the more effective drugs in this category, with the advantage of being oral agents. 
  • Some people with active disease will prefer to start dimethyl- fumarate or, if ‘highly active’, fingolimod in this group.
  • The β-interferons and glatiramer acetate have been used extensively and there is a wealth safety experience 
  • Individuals with relatively quiescent disease and/or who are more risk-averse might choose one of the β-interferons or glatiramer acetate.
  • Individuals with needle phobia may choose teriflunomide, dimethyl fumarate or, if eligible, fingolimod. 
More active relapsing–remitting MS

The formal criteria for high-disease activity are despite interferon-β or glatiramer requires one relapse in the previous year on interferon-β and either (a) ≥1 gadolinium-enhancing MRI lesions or (b) at least nine T2-hyperintensive lesions on cranial MRI.

  • We recommend that patients with more active disease use one of the Category 2 drugs, natalizumab or alemtuzumab. Indirect comparison suggests that alemtuzumab and natalizumab have similar efficacy. 
  • Although alemtuzumab’s licensed indication is much less restrictive,we recommend that, given its potential adverse effects, it should be mainly confined to patients with more active disease.
  • Alemtuzumab and natalizumab are appropriate where one is concerned to achieve high efficacy, despite the more complex safety profile compared to Category 1 drugs.
  • Some people who have experienced relapses despite using a Category 1 agent may be particularly risk-averse or had occasional minor relapses. In such instances, it may be appropriate to change from one to another Category 1 agent.
  • Switching between Category 1 agents because of continued disease activity may be justified on the basis of MRI-proven disease activity alone.
  • Switching from a Category 1 agent to a Category 2 monoclonal antibody is probably justifiable only when there is clinical evidence of high-disease activity despite treatment.
Clinically isolated syndrome
Various disease-modifying treatments can delay the diagnosis of MS in patients with a clinically isolated syndrome
  • Currently, only the β-interferons and glatiramer are licensed for clinically isolated syndrome.
People with MS aged under 18 years of age
We believe that minors aged between 16 and 18 years should be treated according to the above guidelines. 

Children with MS aged <16 should consult with paediatric neurologists with a particular interest in MS.

Primary or secondary progressive MS
None of the current disease-modifying treatments is recommended in non-relapsing secondary progressive MS or in primary progressive MS. Some people with relapsing progressive MS may benefit from disease-modifying treatment.

Recommendations for stopping disease-modifying treatment
Decisions to start or stop treatment should recognise the central importance of patient choice.

We believe it is not feasible to have mandatory stopping criteria that apply in all cases.

Clinicians should consider stopping disease-modifying treatment in the following scenarios:
  • Significant side effects specific to any individual agent should trigger withdrawal of that agent and consideration of an alternative treatment.
  • Development of non-relapsing secondary progressive MS.


  • During pregnancy, disease-modifying treatments should normally be stopped. 
  • We recommend that women stop disease-modifying treatments while trying to conceive unless, the woman’s clinical condition requires treatment.
  • Given the increased risk of relapse, treatment should be restarted early after delivery, depending on discussions concerning breast feeding.

This is a consensus guideline and so not every neurologist will agree with the contents of this !

CoI: Prof G and I are co-authors of these guidelines (and neither of us agrees with every paragraph).

About the author


  • If normalising atrophy is so important, as highlighted on this blog (and I agree that it is, given that it's one of the biggest correlates with disability), why would you issue guidelines that a) don't even mention it and b) seemingly recommends first line treatments, for a majority of patients, which have close to zero impact on atrophy?

    Feels like these guidelines are going to lead to many patients committing to a path which leads to SPMS (for which you have no treatments), when there are drugs which can apparently delay (or maybe even prevent) SPMS when given early.

    Definitely an improvement on what's out there, but as thought-leaders in MS, I would have thought you'd have pushed this a bit more.

    Really, in 2015, knowing what we know, why would a neurologist give anyone interferon beta, the lowest efficacy drug which bears almost no prospect of long term normalisation of atrophy, prevention/delay of SPMS, etc.

    This blog is always saying neurologist/the field in general needs a good kick up the arse and a reality check for being too conservative… And then you go and deliver a paper like this!

    Missed opportunity?

  • Also, "it is not yet clear whether treatment should aim for a target such as No Evidence of Disease Activity"….. WHAT???!!

    In what possible scenario could NEDA not be a better target than EDA?!

    Relapses, MRI activity, progression and atrophy are all signs of active disease, all are associated with irreversible neurological injury, and you're saying it's not cleR whether avoiding this is a sensible target?

    Jeez. As an MS'er reading this, it's not hard to see why patients don't respect their neurologist, or head off to seek treatment abroad.

    Dr G is clearly one of the good guys in the field, and I understand there's politics at play here, but politics over patients is not the way it should be. If you had MS yourself, are you seriously telling me you'd even contemplate beta interferon?

    • i heard profG talking about this last week and in his words he "lost"
      on this one.
      As said it is concensus but as you say where is the ambition.

    • It's good to see acknowledgement of induction or at least aggressive early treatment and the role of patient choice.

  • I second matts point. Fair enough if you are stable on injectables why change but a newly diagnosed young person starting them what?!??@& Its been shown aggressive treatment early in the disease can massively effect the progression and the quality of life for that person. For the life of me I don't understand why all newly diagnosed are not at least being offered alemtuzumab. Fair enough they may decide the side effects outweigh benefits but at least let them make that informed choice and then work down the scale. Neuro's are not even mentioning aggressive treatments to the newly diagnosed…. That's not their choice to make its the person living with the disease and its consequences. Ugh rant over sorry

  • These guidelines are consensus guidelines; developed using a democratic process. We used a modified DELPHI method. At least they are a moving in the right direction. We will eventually get to NEDA; adoption is a slow process.

    • They are a step in the right direction. With the strong focus on patient engagement it would be heartening to see MSers involved in the next review. Would the DELPHI model work in that respect?

  • I'm on Tec, my first DMT after several nasty relapses. I discussed DMT's with my MS nurse and they said alemtuzumab would be considered if first line tablets or injectables were not working. hmm This was end of last year.

  • Dr. G – With teriflunomide's consistent efficacy profile across multiple trials (in RR reduction, MRI, and Disability – which seemed to get overlooked) as well as its well documented and predictable safety profile (including Leflunomide) … when do you think it will get a fair shake? Absolute relapse rate reductions are similar among the 3 oral DMT's as well as GA 3xweek and PEG Interfeon. Also, why does Tecfidera and Fingolimod get a "pass" when evaluating the disease burden in their placebo arms (or the denominator when calculating relapse rate reduction)?

  • I agree with Matt. I cant help but feel this guidelines will prove a barrier to having cat 2 medication with the emphasis they place on high disease activity. Reading them I'm glad I moved to cat 2 when I did as I'm not sure I would meet the criteria now. My shared conversation may have gone somewhat differently.

  • I've read these guidelines a couple of times, and what can I say – the confused ramblings of twenty something, following a familiar waffling speak which is all too familiar. GUIDES AND LINES!

  • Yankee (Sorry, I don't want to call you "Stupid" 🙂 ) Where did you read the MRI/disability data that you cite for Teriflunomide? I wasn't aware that it had any effect on anything other than RR.

    The Lancet Neurology
    Volume 13, Issue 3, March 2014, Pages 247–256

    Table 4 and


    Results of our trial showed that oral, once-daily teriflunomide 14 mg was significantly more effective than placebo at reducing both the annualised relapse rate and the risk of 12 week confirmed accumulation of disability in patients with relapsing forms of multiple sclerosis. The 7 mg once-daily dose also significantly reduced the annualised relapse rate, but had no significant effect on disability progression. Teriflunomide has now been studied in three placebo-controlled trials—a phase 2 study (with a long-term extension),6 and 7 and two large, placebo-controlled phase 3 trials (TEMSO3 and TOWER)—which together show the consistent efficacy of teriflunomide and, along with the established safety and tolerability, confirm a favourable benefit–risk profile for both doses of teriflunomide. Although the adverse event profile is similar for both doses and the significance of the difference in efficacy between groups has not been tested statistically, teriflunomide 14 mg has shown consistently greater efficacy than 7 mg. These data support the use of teriflunomide as an initial therapy for patients with relapsing multiple sclerosis and as an option for patients who are unable to tolerate other disease-modifying therapies.

  • PPMS gets a short shrift as usual. Terribly inspiring this document. (With the emphasis on "terribly".) Nothing about physiotherapy even – and a good physiotherapist can be life changing. Thanks to mine, I'm still walking.

By ProfK



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