MSIF’s recent Atlas of MS survey showed that 72% of countries have major barriers in accessing disease modifying therapies (DMTs) and these barriers are even more pronounced in low and middle-income countries. 70% of low-income countries and 60% of countries in the World Health Organisation (WHO) African region report no licensed MS DMTs available for use. High-efficacy monoclonal antibodies – such as natalizumab, alemtuzumab or ocrelizumab – are particularly poorly available.
‘Off-label’ treatments are those that have been approved for other conditions, but not specifically MS. Off-label DMTs are often more readily available and affordable in health systems, and may provide a treatment option where other DMTs are unavailable or unaffordable. The Atlas of MS showed that off-label use is common – they were used in at least 89 countries. The evidence-base for off-label treatments is different to treatments which have regulatory approval, but they may be the only option in low-resource settings. The question of whether to use off-label treatments is a real issue that health systems, clinicians and people affected by MS face, and we want to support people to understand the benefits and risks, so they can make the best decisions to manage MS.
General principles for the ethical use of off-label DMTs for treating MS
To support work on off-label DMTs for MS, we have published principles for the ethical use of off-label disease-modifying therapies for multiple sclerosis, which have gained wide global support from the MS community.
In summary, the principles state:
- Off-label use of DMTs to treat MS should be driven by the need to protect the person’s health.
- Off-label use should be evidence-driven and considered when on-label DMTs are not tolerated, unsuitable for the best clinical outcome, unavailable or unaffordable.
- Shared decision-making between people with MS and their healthcare professional is especially important when off-label DMTs are considered.
- Appropriate information on health benefits and risks of the off-label DMT should be made available to people with MS by their healthcare professional during the full disease management pathway.
- Outcomes, effectiveness and adverse events when using off-label DMTs to treat MS should be carefully monitored.
Long-term changes needed
We also believe that the following issues need to be addressed in relation to the use of off-label DMTs for MS:
- To support evidence-driven clinical decision-making and reimbursement decisions, guidelines for the use of off-label DMTs to treat MS are needed.
- The regulation of off-label prescribing for MS should be further considered and developed both nationally and internationally to support best clinical practice.
- Regulatory agencies and other organisations should develop measures to facilitate official registration of off-label use of medicines with a positive benefit–harm balance based on adequate evidence.
Guidelines for the use of off-label DMTs for MS
To support evidence-driven clinical decision-making, MSIF decided to collaborate with the McMaster GRADE Center in association with Cochrane Canada, and the Cochrane MS group to develop the methodology and systematically review all available evidence for two commonly used DMTs: azathioprine and rituximab.
In addition, MSIF put together an independent global and multi-disciplinary panel to assess the evidence and make recommendations for the use of these two DMTs in relapsing and progressive forms of MS – MSIF Off-Label Treatments panel (MOLT panel).
The recommendations are specifically aimed at low-resource settings where a range of DMTs are not available and affordable. Low-resource settings include low- and middle-income countries and disadvantaged populations in high-income settings, e.g. uninsured, refugees. Read the full recommendations here.
These recommendations are due to be published as guidelines in late 2023.
How to use off-label recommendations for advocacy
Using off-label treatment guidelines to improve access to treatment in Morocco
In the video below, Najoua Abkari from HANASEP Morocco presents a case study at MENACTRIMS (Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis). The case study focuses on access to treatment in Morocco and explains how the MOLT (MSIF Off-label treatment) recommendations can be used in this context. The presentation is in Arabic with English subtitles.