Tag Archives: safety-netting

Detail, DMTsDetail, Treatment strategy

What are the attributes of the specific DMTs?

Multiple sclerosis (MS) treatment has evolved rapidly, with 11 classes of disease-modifying therapy (DMT) now available in the UK. I will summarise them briefly and explain how they fit within a treatment paradigm for effective and safe use.

Maintenance therapies versus immune reconstitution: what’s the difference?

There is a divide between the two main treatment philosophies: maintenance ̶ escalation versus immune reconstitution therapies (IRTs).

An IRT is given as a short course – a one-off treatment in the case of autologous haematopoietic stem cell transplantation (AHSCT) or intermittently for alemtuzumab, cladribine or mitoxantrone. IRTs are not given continuously, and additional courses are given only if inflammatory activity recurs. IRTs can induce long-term remission and, in some cases, potentially a cure.

Maintenance therapies, by comparison, are given continuously without an interruption in dosing (‘continuous’ administration may be daily, one or more times weekly, monthly or even once every few months). Although maintenance therapies can induce long-term remission, they cannot, by definition, result in a cure. The recurrence or continuation of inflammatory activity indicates a suboptimal response to treatment and typically requires a treatment switch. Ideally, this switch should be an escalation to a more effective class of DMT.

An article in our list of key questions, entitled How do I want my MS to be treated?, provides a more detailed comparison of maintenance and IRT therapies, including frequency of administration, efficacy, risks, use in pregnancy, vaccine response and potential for a cure.

The DMTs currently licensed in the UK (in August 2024) are listed in the table under the relevant category.

table format updated 180625 SS

Disease-modifying therapies for MS licensed in the UK. *Please note, Bonspri is available in other markets but not the UK.

How effective are the different DMTs?

The measures used to assess the effectiveness of a DMT include its ability to reduce or prevent relapses, focal inflammatory activity (that is, new or enlarging lesions) on magnetic resonance imaging (MRI), and disability progression. Additional factors that can help to assess the relative efficacy of DMTs include the proportion of clinical trial subjects who experience improvement in disability and the impact of the treatment on brain volume loss.

The MS-Selfie InfoCards are an easy-to-use resource to help people with MS compare the key features of each DMT. They contain bite-sized information designed to aid treatment choices and an overview of the key aspects of each DMT.

Efficacy of the licensed DMTs for MS can be visualised as pyramid, with the moderately effective treatments at the bottom and the more effective approaches at the top. What determines the most appropriate DMT efficacy level for an individual depends on several factors, such as baseline prognostic profile, family planning requirements, local or national treatment guidelines, socioeconomic factors, consideration of any co-existing illnesses, cognitive impairment, risk aversion and lifestyle issues.

Pyramid format updated 180625 SS

UK licensed DMTs for MS, in ascending order of efficacy.
HSCT/AHSCT, haematopoietic stem cell transplantation/autologous haematopoietic stem cell transplantation.

What is the goal of treatment? Introducing NEIDA as a target

In the past, we used no evident disease activity (NEDA) as a treatment target. ‘Disease activity’ included progression or disease worsening independent of relapse activity (termed smouldering MS). Although some of the more effective DMTs may modify this stage of the disease, many neurologists feel uncomfortable switching or stopping a DMT based simply on smouldering MS disease activity. 

Relapses and ongoing focal MRI activity are associated with a worse short-term to intermediate-term prognosis. These observations have led to the increasing adoption of ‘no evident inflammatory disease activity’ (NEIDA) as a new treatment target. For more information about treatment targets, please see the article in our key questions, Do I understand the concepts of treat-2-target and NEDA?

Many healthcare professionals (HCPs) remain sceptical of using NEIDA as a treatment target, fearing that this could lead to more people with MS being on ‘riskier’ high-efficacy therapies. However, achieving long-term remission, or NEIDA, is a well-established treatment target in other autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. People with MS treated-to-target of NEIDA from the outset do better than those whose treatment is escalated following breakthrough disease (at a clinical or subclinical/MRI level)1. I would, therefore, strongly encourage people with MS and their HCPs to adopt NEIDA as an initial treatment target.

Flipping the pyramid

The effectiveness, or relative effectiveness, of individual DMTs becomes less critical in the context of a treatment target of NEIDA. Choosing a DMT with a lower efficacy rate simply means that a greater proportion of treated people with MS will need to be switched to higher efficacy therapies over time to achieve NEIDA. We refer to the latter of these three approaches – starting with high-efficacy treatment – as flipping the pyramid. In recent trials of alemtuzumab, ocrelizumab, ofatumumab and ublituximab, people with MS randomised to 2 years of lower efficacy DMTs (interferon-beta-1a or teriflunomide) had poorer outcomes than those receiving highly active therapy from the outset. Real-world data from registries also support this; groups of people with MS with delayed access to high-efficacy DMTs did worse than those who received high-efficacy treatments early.1,2

Horizontal versus vertical switching

If we consider the conventional step care paradigm, people with MS who switch horizontally from interferon-beta to glatiramer acetate, or vice-versa (i.e. from one moderate efficacy DMT to another moderate efficacy DMT) do less well than those who switch vertically to fingolimod, a highly effective DMT. Similarly, people with MS escalating to natalizumab, a very high-efficacy DMT, do better than those being escalated to the less effective, but still high-efficacy, DMT fingolimod. 

Continuous and intermittent immunosuppression

Another useful way of classifying DMTs is whether they are immunosuppressive, that is, they reduce the activation, or effectiveness, of the immune system. Drug regulators stipulate that a drug may be classified as immunosuppressive if it (1) causes significant lymphopaenia (low lymphocyte count) or leukopenia (low white blood cell count), (2) is associated with opportunistic infections, (3) reduces the antibody and immune response to vaccines and (4) increases the risk of secondary malignancies.

The duration and intensity of immunosuppression further determine the risks. For example, short-term or intermittent immunosuppression associated with IRTs front-loads the risks, which are substantially lower once the immune system has reconstituted itself. In comparison, long-term continuous or persistent immunosuppression, which occurs with some of the maintenance DMTs, accumulates problems over time, particularly opportunistic infections and secondary malignancies. You can read more detail on this topic in the key question How immunosuppressed am I? The following table summarises the main attributes of intermittent and persistent immunosuppression.

How immunosuppressed are you table updated format 180625 SS

The main characteristics of continuous (persistent) and short-term (intermittent) immunosuppression. Modified from Giovannoni, Curr Opin Neurol.2
AHSCT, autologous haematopoietic stem cell transplantation; PML, progressive multifocal leukoencephalopathy.

Adverse effects, monitoring and risk reduction

The complications associated with immunosuppression vary from DMT to DMT. Each individual drug summary in the DMTs section of MS-Selfie contains detailed information about the main adverse events, key monitoring requirements, use (or contraindication) during pregnancy and breastfeeding, and response to vaccines. The MS-Selfie InfoCards provide bite-sized summaries of several practical aspects, including side effects, to enable easy comparison of any treatments you are considering; some of this information is collated below for easy reference.

Short-term versus long-term adverse effects

Each drug has been given scores from 1 to 10 based on published analyses of its short-term and long-term side effects. Short-term refers to side effects that emerge when a treatment is started and decrease in severity or disappear within days or weeks. A well-known example of short-term side effects on starting interferon-beta is flu-like symptoms that typically abate within 4 ̶ 8 weeks.

A long-term side effect persists for months or doesn’t disappear on continuing the DMT. Examples include intermittent but persistent flushing after taking dimethyl fumarate, or low B lymphocyte counts with anti-CD20 therapies that may lead to low antibody or immunoglobulin levels (hypogammaglobulinaemia).

A low score denotes few or rare side effects; a high score denotes many or frequent side effects. The score does not correlate to a percentage. More information can be found in each drug summary and the manufacturer’s Summary of Product Characteristics.

Scores for short-term and long-term side effects assigned to the individual DMTs summarised in the MS-Selfie InfoCards, based on a published network meta-analysis.3
Alem, alemtuzumab; GA, glatiramer acetate; HSCT, haematopoietic stem cell transplantation; IFN-beta; interferon-beta; Nat, natalizumab.

Monitoring and risk reduction

Numerous tests are carried out at the start of treatment, and ongoing monitoring is required for many factors, to reduce the risk from adverse events. The key question, How can I reduce my chances of adverse events on specific DMTs?, explains what needs to be done at the start of DMT administration (baseline) and during subsequent monitoring. The specifics vary from DMT to DMT; please refer to the individual summaries for details such as baseline tests, follow-up, infection prevention, cancer risk, pregnancy, breastfeeding and vaccination. It is important to remember that all licensed MS DMTs have had a thorough risk ̶ benefit assessment, and their benefits are considered to outweigh the potential risks.

Administration and other practical considerations

Routes and frequency of administration

The MS-Selfie InfoCards contain a symbol for each DMT, showing how it is administered. Some DMTs are available in more than one formulation (e.g. tablets and injection). The frequency of administration varies greatly from DMT to DMT; please consult the relevant summary in the DMTs section and discuss your preferences and priorities with your MS HCP.

The route of administration for each drug in the MS-Selfie InfoCards is clearly identified by the relevant symbol. (If a DMT is available in more than one formulation, there is a separate card for each delivery route.)

Number of clinic visits

It may be important for you to consider the frequency of clinic visits. This will depend on factors such as the delivery route of your DMT, the monitoring requirements of the drug regulators and the risk of specific side effects. The table below summarises the assessments from the MS-Selfie InfoCards. This is another factor to consider in discussions with your MS HCPs about the most appropriate DMT for you.

Conclusions

People with MS must understand the objectives of MS treatments and the different treatment strategies currently available to achieve these objectives. Although the MS therapeutic landscape is complex and hence may seem overwhelming, framing the choices using a relatively simple construct should help each individual to make informed decisions about managing their MS. MS-Selfie aims to guide you in the process of deciding on the most appropriate therapeutic strategy and specific DMT for treating your disease.

References

  1. Rotstein D, et al. Association of No Evidence of Disease Activity with no long-term disability progression in multiple sclerosis: a systematic review and meta-analysis. Neurology 2022;99:e209̶ ̶ 20.
  2. Giovannoni G. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol 2018;31:233 ̶ 43.
  3. Samjoo IA, et al. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res 2021;10:495–507.
Clinical decisions, Cognition and mental health

Medical gaslighting – what is it, and how to avoid it?

Doctors have a long history of ignoring patients’ symptoms and complaints. In MS, this phenomenon tends to affect the so-called ‘hidden’ symptoms and related problems that are difficult to treat. 

Key points

  • Medical ‘gaslighting’, where healthcare professionals (HCPs) dismiss or downplay a patient’s symptoms, is an issue that patients and HCPs should be aware of. It affects women more than men.
  • Safety-netting is a legitimate strategy whereby the HCP and the patient adopt a wait-and-see approach to avoid over-investigation and overdiagnosis. It is part of a shared decision-making process and should not be interpreted as gaslighting.
  • Medical gaslighting can be subtle, but useful strategies exist for detecting and avoiding it.
  • If you are being gaslighted, despite efforts to push back, don’t be afraid to make your healthcare system aware of the problem rather than suffer in silence.

A case scenario

Whenever I see my neurologist, he seems to fob me off as if I don’t have a problem. He disagrees with me when I tell him that my MS is getting worse. He tells me I am not getting worse as my MRI is stable and my neuro exam is unchanged. He doesn’t believe me when I tell him that I am becoming more forgetful and that my fatigue is affecting the quality of my work.  

Origin of the term ‘gaslighting’

The volume of medicolegal case studies where doctors have ignored patients’ symptoms and complaints illustrates the extent of a problem that is now being referred to as medical gaslighting. Medical gaslighting may occur if:

  • your symptoms or concerns are dismissed of ignored without cause
  • your symptoms are dismissed as being normal, without explanation
  • you are made to feel your healthcare provider is blaming you.

The term ‘gaslighting’ comes from the 1944 film Gaslight starring Ingrid Bergman. The movie tells of a man who manipulates his wife to such an extent that she begins to doubt her own sanity. Since then, the term gaslighting has been used to describe emotional abuse that makes someone question their version of reality. People are beginning to share their personal experiences of medical gaslighting on social media with the hashtag #medicalgaslighting. 

Prevalence and severity of medical gaslighting

An article in the British Medical Journal (BMJ) suggests women are more likely than men to suffer from medical gaslighting, particularly with ‘health problems such as endometriosis, fibromyalgia, and irritable bowel syndrome’.1 Worryingly, the article states: ‘when compared with men, women face longer waits to be given a diagnosis of cancer or heart disease’. The article goes on to imply that medical gaslighting is becoming more common and the term has been ‘used widely in connection with long COVID, particularly early on in the pandemic’, when some patients who were still experiencing symptoms months after infection with SARS-CoV-2 thought they were not treated seriously or investigated fully.

A short online survey I did among MS-Selfie readers in 2022 revealed that 88% of 423 responders reported being gaslighted.

Responses to the survey question, ‘Have you ever experienced medical gaslighting in relation to your MS?’ (based on results from 423 MS-Selfie readers).

I am probably guilty of medical gaslighting too; in some cases, this may be deliberate. Many patients come to me with pages of problems, and I simply don’t have the time to deal with all of them. Time, or more correctly, lack of time is therefore one reason for medical gaslighting. Another is lack of knowledge or experience and not being able to admit you don’t know. However, the most worrying reason is the power dynamic, with HCPs wanting to be in control or remain in control. 

MS-Selfie as an initiative tries to address this power dynamic by giving you useful information to self-manage your MS – or at least to ask the right questions. 

Safety-netting

I suspect safety-netting may be misinterpreted as gaslighting. Safety-netting describes activities both within the HCP consultation and at healthcare systems levels (diagnostic and treatment algorithms) to avoid over-investigation and overdiagnosis. Many symptoms are non-specific and because of uncertainty the HCP and the patient adopt a wait-and-see approach. The patient is given clear instructions on how to identify the need to seek further medical help if their condition fails to improve, changes, or if they have ongoing concerns about the problem. Safety-netting is considered good clinical practice. A recent BMJ article2 on safety-netting makes the following points:

  • Aggressively treating or investigating all patients with early undifferentiated illness is poor medical practice and can be harmful.
  • Time is an important diagnostic tool but creates a period of uncertainty and risk for patients with serious underlying conditions.
  • Safety-netting can help mitigate this risk, and a traffic light framework provides a structure for delivering safety-netting advice.

The point about safety-netting is that it needs to be done as a part of a shared-decision making process and it should therefore not be interpreted as gaslighting. 

How to identify and tackle medical gaslighting

A New York Times article on medical gaslighting warns that it can be subtle, and lists some red flags to watch for.3 

  1. Your HCP continually interrupts you, doesn’t allow you to elaborate and doesn’t appear to be an engaged listener.
  2. Your HCP minimises or downplays your symptoms, for example questioning whether you have pain.
  3. Your HCP refuses to discuss your symptoms.
  4. Your HCP will not order key investigations to rule out or confirm a diagnosis.
  5. You feel that your HCP is being rude, condescending or belittling. Your symptoms are blamed on a mental problem, but you are not provided with a mental health referral or screened for such a problem.

Now that we have recognised medical gaslighting as a significant problem in MS, please don’t allow a neurologist to gaslight you. The New York Times article suggests practical steps you can take to prevent this. 

  • Keep detailed notes and records. Patient-held notes transform consultations and force you to become a partner in your healthcare.
  • Record the consultation. Many HCPs don’t like this; just tell them you must listen to the conversation again to ensure you don’t forget things or miss important information. You will be surprised how this changes the HCP’s behaviour. 
  • Ask questions. Then ask some more. And don’t be fobbed off; if you are dissatisfied with the answer, ask the question again. 
  • Take someone with you for support. Having a witness during the consultation has a similar effect to recording the conversation or documenting it with notes. 
  • Focus on your most pressing issues to make the best use of your consultation time. If your HCP is pressed for time, say you understand, but you would like to prioritise the following issues today. This helps you to frame the limits of the consultation and promote a two-way discussion. Also, don’t expect the HCP to have all the answers at their fingertips, but do expect them to come back to you later with the answers.
  • Try and pin down the next steps for your problem; ask what the action points are. For example, if the MRI shows this, how will that change my management? Do I need further investigations? How soon should I switch treatments?

If you are still being ignored, here are some of your options.

Get a second opinion and ask to switch to a new HCP
Look to support groups or forums. Many MS charities have helplines where you can discuss these issues
Appeal to a higher authority, the person above your HCP (their line manager). In the NHS, we have a straightforward procedure for patients to complain or question their care. It is called PALS (Patient Advice and Liaison Service)

Some courses of action open to you if you experience medical gaslighting.

Abuse, manipulation, gaslighting and delaying a diagnosis are potentially reportable events which HCPs need to know about. Therefore, make your healthcare system aware of the problem rather than suffer in silence. 

Healthcare systems and the medical professions

We need to include medical gaslighting as part of the medical curriculum so that HCPs are made aware of it during their training. HCPs must buy into the model of patients being equal partners in the diagnosis and management of their disease. The paternalistic or older patronising model of healthcare where the HCP knows best is outmoded.

Gaslighting is another form of abuse or discriminatory behaviour, no different from sexism, racism or ageism. This raises the question, is it deliberate or an institutional problem, i.e. part of the dominant medical culture? I suspect the latter, and this is why it will need a wider campaign to tackle the problem, with clearly defined carrots (incentives/rewards) and sticks (disincentives/punishment) to change our behaviour. 

References

  1. Wise J. Sixty seconds on . . . medical gaslighting. BMJ 2022;378:o1974.
  2. Edwards PJ et al. Safety-netting in the consultation. BMJ 2022;378:e069094.
  3. Caron C. Feeling dismissed? How to spot ‘medical gaslighting’ and what to do about it. New York Times, 29 July 2022.