Am I eligible for treatment with a DMT?

Eligibility for treatment with with a DMT depends on many factors, principally:

• the licence the drug receives from the regulators in your country, e.g. European Medicine Agency (EMA) or the Federal Drug Administration (FDA);
• then the payers or the organisation who pay for the DMT, e.g. NHS or your medical insurance company;
• and finally national, regional or local guidelines, e.g. Association of British Neurologists guidelines.

Definition of the eligibility factors:

• Regulators decide in which group of pwMS the DMT should be used.
• Payers hold the purse strings and make a cost-effective assessments to try and optimise the use of the drug in clinical practice.
• Guidelines are typically pragmatic and usually based on consensus. Guidelines are to help HCPs use the DMTs in the most appropriate way with a particular healthcare system. Guidelines often go much further than the regulators and payers in that they try and address potential ambiguities in the prescribing of DMTs.

In the NHS in England we have to abide by NHS England's guidelines that are based on NICE technology appraisals, NICE standards of care and the Association of British Neurologists. To navigate the specifics of the eligibility criteria is quite complex. However, a simpler way of looking at this to define how active your MS is. There are four levels of disease activity:

1. Inactive MS - not eligible for DMTs
2. Active MS - eligible for so called platform therapies and alemtuzumab and, potentially, ocrelizumab
3. Highly active MS - eligible for all therapies except natalizumab
4. Rapidly-evolving severe MS - eligible for all DMTs

In addition, the NHS allows MSers to be treated with haematopoietic stem cell transplantation or HSCT. At present there are no official NHS or national guidelines covering HSCT. Therefore you need to ask about local eligibility guidelines.

Advanced MS

NHS England also has a disability cut-off in that MSers who are wheelchair users are not eligible for DMTs. The reason for this is that MSers with more advanced MS have generally been excluded from phase 3 clinical trials and hence there is no data to support the notion that licensed DMTs work in this group of patients.

In addition, there's a persistent medical dogma which needs debunking: that more advanced MS has reduced inflammation, or is ‘non-inflammatory’. There are clinical, imaging and pathological data that show inflammation still plays a large, and probably a major, role in advanced worsening MS. Therefore not to target more advanced MS with an anti-inflammatory is counterintuitive, and may explain why so few monotherapy neuroprotective trials have been successful. Now that ocrelizumab has been licensed for primary progressive MS this may form the platform for future add-on trials.

It is important to acknowledge that reserve capacity (in particular neuronal systems) plays an important part in how MS worsens. Neuronal systems with reserve are more likely to be able to recover function and hence show a treatment effect compared to neuronal systems in which reserve capacity is exhausted. In the latter systems, it will simply take longer to show a treatment effect; I refer to this as therapeutic-lag. These observations could be explained by the length-dependent axonopathy hypothesis of worsening MS; i.e. progressive MS manifests initially in pathways that have the longest axons (bladder and lower limb pyramidal function).

This means that we should focus more on the arm-and-hand function as a primary outcome in MSers who have already lost too much neurological function in their lower limbs (EDSS>=6.0). Once someone with MS has lost lower limb function and become a wheelchair-user, they still have neuronal systems that are potentially modifiable, for example upper limb, bulbar and visual function. In fact, there is an extensive evidence base showing that several licensed DMTs can slow the worsening of upper limb function despite subjects having advanced MS. I feel very strongly about this point and I am keen to argue for future trials in advanced MS to include wheelchair users with a focus on upper limb function as the primary outcome measure. What keeps pwMS independent and functioning in society is arm and hand function.