MS-Risk Calculator version 3.0

The overall odds ratio for family history of any autoimmune disease ranges from 1.4 to 2.0 across studies, suggesting shared genetic susceptibility and potentially common environmental triggers.

When I published my MS risk calculator, I was asked about a family history of other autoimmune diseases. I have done a SciSpace search, and a positive family history does increase the risk of someone developing an autoimmune disease. You are welcome to download the SciSpace review here. The following is the summary.

Executive Summary

This report systematically examines whether having a family history of autoimmune diseases other than multiple sclerosis (MS) increases the risk of developing MS. Based on analysis of 30 highly relevant studies from a comprehensive literature search across multiple databases, the evidence indicates that family history of non-MS autoimmune diseases is associated with a modest but statistically significant increase in MS risk. The most robust evidence comes from large population-based cohort studies, particularly from Scandinavian registries, which demonstrate elevated risks for MS among first-degree relatives of patients with various autoimmune conditions. Specific autoimmune diseases showing the strongest associations include type 1 diabetes, inflammatory bowel diseases (particularly Crohn’s disease), thyroid disorders, rheumatoid arthritis, and psoriasis. The overall odds ratio for family history of any autoimmune disease ranges from 1.4 to 2.0 across studies, suggesting shared genetic susceptibility and potentially common environmental triggers. These findings have important implications for MS risk stratification, early detection strategies, and understanding the broader autoimmune disease spectrum.

As a result of this review, I have added a family history of autoimmune disease to the calculator and now include a version number and update date so you can keep track as the calculator evolves over time.

This is the actual link to the calculator: https://claude.ai/public/artifacts/1c09d603-6acf-4abf-8fcf-3f24f30363b4

Some of you have asked why this risk calculator is not being used. The reasons are simple. It has not been validated, and at present, we have no data to support an intervention to lower the risk of developing MS. From an individual perspective, someone at high risk could modify certain lifestyle factors and exposures and take vitamin D supplements. However, we cannot be sure at present if these interventions lower the risk of getting MS.

Could the calculator be used to decide who should have further investigations, i.e. for example, be examined by a neurologist or an AI-empowered automaton (robotic neurologist) or have an MRI scan, or require further studies? But this is exactly the question the FIND-MS initiative is trying to answer, but in a cost-effective way?

If one of your family members, for example, one of your children, had a high chance of developing MS, would you want them to be screened for asymptomatic MS? If they had asymptomatic MS, they may be eligible for a clinical trial or treatment. I say treatment because a large number of neurologists are now offering people with RIS (radiologically-isolated syndrome) or asymptomatic MS treatment. At present, the NHS England guidelines don’t allow us to treat people diagnosed with RIS. This is why I was arguing for doing a clinical trial of cladribine in RIS. The good thing about cladribine is that it is relatively safe, and it could potentially be a one-off treatment. The other maintenance DMTs must be administered indefinitely, and many are associated with chronic immunosuppression. I can’t imagine many people with asymptomatic MS will sign up for lifelong therapy with side effects that accumulate.

Please note that we are far away from implementing any MS at-risk screening programme. The following are the UK National Screening Committee (UK NSC) criteria for appraising the viability, effectiveness and appropriateness of a population screening programme. As you can see, the MS-Selfie MS-risk calculator will not fulfil these criteria.

The condition

1. The condition should be an important health problem as judged by its frequency and/or severity. The epidemiology, incidence, prevalence, and natural history of the condition should be understood, including the progression from latent to declared disease, and/or there should be robust evidence of an association between the risk or disease marker and serious or treatable disease.

2. All the cost-effective primary prevention interventions should have been implemented as far as practicable.

3. If carriers of a mutation or persons at risk are identified through screening, the natural history of people with this status should be understood, including its psychological implications.

The test

1. There should be a simple, safe, precise and validated screening test or tool.

2. The distribution of test values in the target population should be known, and a suitable cut-off level should be defined and agreed upon.

3. The test, from sample collection to delivery of results, should be acceptable to the target population.

4. There should be an agreed policy on further diagnostic investigation for individuals with a positive test result and on the choices available to them.

5. If the test is for a particular mutation or set of genetic variants, the method for their selection and the means through which these will be kept under review in the programme should be clearly set out.

The intervention

1. There should be an effective intervention for patients identified through screening, with evidence that pre-symptomatic intervention leads to better outcomes for the screened individual compared with usual care. Evidence on wider benefits of screening, for example, those affecting family members, should be taken into account where available. However, where there is no prospect of benefit for the individual screened, then the screening programme should not be further considered.

2. There should be agreed-upon, evidence-based policies specifying which individuals should be offered interventions and which interventions are appropriate.

The screening programme

1. There should be evidence from high-quality randomised controlled trials that the screening programme is effective in reducing mortality or morbidity. Where screening is aimed solely at providing information to allow the person being screened to make an ‘informed choice’ (such as Down syndrome or cystic fibrosis carrier screening), there must be evidence from high-quality trials that the test accurately measures risk. The information provided about the test and its outcome must be valuable and readily understood by the individual being screened.

2. There should be evidence that the complete screening programme (tests, diagnostic procedures, treatment/intervention) is clinically, socially, and ethically acceptable to health professionals and the public.

3. The benefit gained by individuals from the screening programme should outweigh any harms, such as overdiagnosis, overtreatment, false positives, false reassurance, uncertain findings, and complications.

4. The opportunity cost of the screening programme (including testing, diagnosis and treatment, administration, training, and quality assurance) should be economically balanced relative to total medical care expenditure (value for money). Assessment against this criterion should have regard to evidence from cost-benefit and/or cost-effectiveness analyses and have regard to the effective use of available resources.

Implementation criteria

1. Clinical management of the condition and patient outcomes should be optimised in all health care providers prior to participation in a screening programme.

2. All other options for managing the condition should have been considered (such as improving treatment or providing other services), to ensure that no more cost-effective intervention could be introduced or current interventions increased within the resources available.

3. There should be a plan to manage and monitor the screening programme, along with an agreed set of quality assurance standards.

4. Adequate staffing and facilities for testing, diagnosis, treatment and programme management should be available prior to the commencement of the screening programme.

5. Evidence-based information explaining the purpose and potential consequences of screening, investigation, and preventive intervention or treatment should be made available to potential participants to assist them in making an informed choice.

6. Public pressure to broaden eligibility criteria to reduce the screening interval and increase the sensitivity of the testing process should be anticipated. Decisions about these parameters should be scientifically justifiable to the public.

I hope you found the SciSpace review helpful. Please feel free to ask questions.

For those of you concerned about my reference to an AI-empowered automaton (a robotic neurologist), I urge you to read my three-part short story on the future of neurology.

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