Tag Archives: antibiotic

Bladder and bowel, Intimate issues

Detecting and preventing urinary tract infections

Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress. I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.

Urinary tract infection and disease progression

Infections, both viral and bacterial, are a known trigger of relapse. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce urinary tract infections. You can do this in several ways, such as increasing the frequency of ISC.

Drinking plenty of liquids to flush the bladder reduces infection rates. Changing the pH of your urine by drinking citric acid (citro soda or lemonade) also helps. Making your urine more alkaline or more acidic may work, depending on the bacterial species colonising your bladder. Cranberry extract, for example, contains proanthocyanidins, a substance that reduces bacterial colonisation of the bladder. (You need to use the extract and not the juice because the proanthocyanidin concentration in the juice is too low to have an effect.)

Another very effective option (but infrequently used) is a bladder instillation with a liquid containing sodium hyaluronate (Cystistat), which replaces the glycosaminoglycan layer, or glycocalyx, of the bladder wall. This makes it difficult for bacteria to stick to the bladder wall to cause infections and is one way of preventing bacterial biofilms, or slime, from forming. Biofilms are a significant problem because they prevent antibiotics from reaching the bacteria to kill them and act as a breeding place for recurrent infections.

Urinary antiseptics are antibiotics, given in low concentrations, that may help to reduce urinary tract infection rates. They are typically administered in tablet form; they work by being concentrated by the kidneys and making the urine antiseptic, which helps to prevent or treat urinary tract infections. The agents I use currently are trimethoprim, cephalexin and nitrofurantoin. (Methenamine, another urinary antiseptic, is not readily available in the UK due to supply issues.) Cycling their use, every 3 ̶ 4 months, prevents the bladder bacteria from becoming resistant to a specific antibacterial. We have stopped using nalidixic acid and other drugs in the oxolinic acid class because they are associated with tendonitis and tendon ruptures.

Interpretation of urine dipstick results

Early detection of urinary tract infections (UTIs) means that they can be treated promptly to prevent symptomatic infection or complications such as pyelonephritis (kidney infection) and septicaemia (a common cause of death in people with advanced MS). Dipstick testing can be carried out at home, as part of self-management of your MS. I recommend doing dipstick monitoring once or twice a week, not daily. If positive, you must drop off a clean urine sample to your healthcare provider for proper laboratory analysis (microscopy, culture and sensitivity). This is to confirm the presence of a UTI, to culture and isolate the bacteria causing the infection, and to test the sensitivity of the bacteria to antibiotics. You must send your urine specimen for analysis before you start antibiotics. 

For UTI monitoring, the leukocyte and nitrite tests are the most important, with backup from the protein, blood and pH tests. The guidance in the table below explains how to interpret some of the key dipstick test results relevant to UTIs and what the different readings on a typical urine dipstick mean. You need to wait up to 2 minutes to read the results; if in doubt, take a picture of the test strip with your mobile phone and email it to your HCP for interpretation.

Dipstick results

Guidance to help you interpret the dipstick results relevant to urinary tract infection (UTI). You should wait for up to 2 minutes before reading the results (2 minutes for leukocytes, at least 60 seconds for other results shown here).
*If you have been treated with alemtuzumab, new-onset proteinuria in the presence of blood may indicate Goodpasture’s syndrome, a rare autoimmune complication of alemtuzumab treatment. Please consult your HCP.
UTI, urinary tract infection.

The image below shows what the different readings on a typical urine dipstick mean; the readings for white blood cells, nitrite, protein, pH and blood are important for detecting the presence of a UTI (more information is in the Table above). Further details about readings for urobilinogen,  specific gravity, ketone levels, bilirubin and glucose are available in my newsletter entitled How to interpret a urine dipstick result.

An example of results from a urine dipstick test; the readings most relevant to interpreting urinary tract infections are white blood cells, nitrite, protein, pH and blood. Information about additional results from dipstick testing are available in my newsletter entitled How to interpret a urine dipstick result.

Bladder and bowel, Intimate issues

Intimate issues: bowel disorders

Here I discuss why people with MS develop problems with their bowel function and I offer straightforward advice on how to manage constipation, diarrhoea and other MS-related bowel problems.

Key points

  • Many people with MS experience a bowel disorder as a result of changes within the central nervous system that may affect the rectal and anal muscles.
  • Agents that increase the muscular action of the bowel can help to treat constipation.
  • Medications for some MS symptoms can increase constipation and may need to be reviewed.
  • Faecal impaction associated with constipation is a serious problem that may need hospital treatment.
  • Small intestinal bacterial overgrowth (SIBO) from faecal impaction may occur if the bacteria of the small intestine increase above normal values, producing harmful toxins.
  • SIBO is associated with unpleasant symptoms including abdominal bloating, pain, anaemia, irritable bowel syndrome, constipation, diarrhoea and faecal impaction.
  • Bowel hypomobility and any faecal impaction underlying SIBO need to be addressed, and antibiotics may be required to reduce the abnormal bacteria in the bowel. A gut health programme and dietary review are important for long-term management.
  • Being incontinent of faeces in public is highly embarrassing and may lead to severe anxiety and social isolation.
  • Faecal urgency or incontinence are best treated by developing a bowel routine and trying to evacuate your bowels in a controlled environment and at a regular time of day.
  • Regular rectal or transanal irrigation can significantly improve the quality of life in such cases.
  • MS should be treated early with effective DMTs, to avoid or delay damage to the neuronal pathways that control bowel function.

Many people with MS experience bowel disorders, including constipation, faecal hesitancy (difficult initiating a bowel action), incomplete emptying, faecal urgency, urgency incontinence, overflow diarrhoea, excessive bloating and excessive flatus. Understanding the causes of rectal and anal dysfunction in patients with MS can help us to select the most relevant therapies to target specific symptoms.

People with MS who experience constipation generally have a loss of sphincter tone (strength) at rest and during contraction compared with non-MS patients. In faecal incontinence, rectal sensitivity threshold is reduced, meaning that when faeces enter the rectum the threshold at which the defaecation reflex is triggered is lower than normal. There is also evidence that the coordination of the pelvic floor following contraction of the anal sphincter is abnormal in people MS. Pelvic floor exercises may help with this.

Management of constipation

Bowel dysfunction, particularly constipation, is common in MS. Constipation occurs because the MS bowel is sluggish due to reduced motility (i.e. the muscles or nerves do not work as they should). The management aim is usually to encourage regular bowel action, either daily or at least every two days.

Prokinetic agents that increase the muscular action of the bowel can help to treat constipation. The prokinetic agent I prescribe most often is senna. If this fails, other options include bisacodyl, co-danthrusate, sodium picosulfate or prucalopride; these agents work by stimulating the nervous system in the bowels. Prokinetic agents often need to be taken with bulking (fibre) and loosening (liquid) agents. Bulking agents include methylcellulose, psyllium or ispaghula husks, and sterculia granules. Loosening agents keep liquid in the bowel, causing water to be retained with the stool; examples include lactulose, polyethylene glycol (Movicol), magnesium hydroxide and magnesium sulphate (Epsom salts).

Cyclical use of laxatives can contribute to ongoing constipation: you use laxatives to treat your constipation, the laxatives cause diarrhoea, so you stop taking them. You then become constipated again, and the cycle repeats itself. 

If you experience bladder incontinence, dehydrating yourself to control your bladder problems can make constipation worse; you must drink adequate quantities of water throughout the day. Similarly, anticholinergic drugs used for treating urinary frequency and urgency and treatments for pain and spasticity may all make constipation worse. Therefore, if you are constipated your medications for other symptoms of MS need to be reviewed. 

Faecal impaction

Over time, the bowels may become impacted with faeces, and a hard, stony mass of compacted faeces forms (known as a faecolith). The gut bacteria may then overgrow and liquefy the stool above this impacted faecolith, bypass the impaction and cause diarrhoea. A typical history of faecal impaction includes periods of constipation punctuated by episodes of diarrhoea. If you suffer from chronic constipation and intermittent diarrhoea, you should contact your health team for help. Faecal impaction is a serious problem and often warrants treatment in hospital.

Below are some tips for managing MS-related constipation.

  1. Optimise your diet by eating lots of fibre.
  2. Don’t dehydrate yourself. Drink plenty of water; be aware that caffeine and alcoholic beverages are not hydrating. Both cause the kidneys to make more urine (diuresis) and are dehydrating.
  3. Try to eliminate the concurrent use of medications that exacerbate constipation (anticholinergics and opioids).
  4. Exercise regularly; the anticipation of exercise and exercise itself stimulate a defaecation reflex.
  5. If you need to use laxatives, start with a prokinetic agent that stimulates the bowel to move, such as senna; then add in bulking agents (e.g. psyllium husks or other fibre substitutes) followed by liquifying agents (lactulose or polyethylene glycol).
  6. Don’t suppress the need to go to the toilet; many people with chronic constipation have learnt bad habits (such as not using toilets that are unfamiliar to them).
  7. Try to develop a daily bowel routine, for example, by having a bowel movement at a particular time (ideally in the morning). This may require you to stimulate a bowel movement, perhaps by eating something, drinking a caffeine-containing drink, anal stimulation (anal plug), using glycerine suppositories, mini-enemas or (if necessary) an anal irrigation system. An anal plug is used to stimulate the colonic emptying reflex and is removed before you have bowel action.

These final recommendations may sound extreme, but they are essential steps to prevent faecal impaction. They may also give you the confidence to go out knowing that you can avoid faecal urgency and incontinence.

Small intestinal bacterial overgrowth (SIBO)

People with MS with bowel dysfunction may develop small intestinal bacterial overgrowth (SIBO), which is defined as an increase in the bacterial content of the small intestine above normal values. Some studies show that four in every 10 people with MS have SIBO; it is also detected in approximately one-third of patients with gastroenterological complaints who undergo a breath test. Proton pump inhibitors (omeprazole and related drugs) and smoking are risk factors for developing SIBO. The risk of SIBO increases with age and does not depend on gender or race.

SIBO is associated with dyspepsia, abdominal bloating, abdominal pain, anaemia, irritable bowel syndrome, functional constipation, diarrhoea and faecal impaction. A slowdown in your bowel transit time with SIBO decreases the normal clearance of bacteria from the small intestine. This slowdown is due to changes in the motility of the intestine, which is almost universal in people with MS.

Risks from SIBO

SIBO may damage the intestinal surface or mucosa of the bowel, because the bacteria can produce harmful toxins. This can result in leaky gut syndrome and acquired lactose intolerance. The leaky gut syndrome is controversial and associated with many symptoms that may overlap with MS-related symptoms. Leaky gut syndrome is not medically defined, and no specific tests or treatments are available. In comparison, acquired lactose intolerance occurs when someone loses the ability to digest lactose, the main sugar in milk, which causes them to develop diarrhoea, gas and bloating after eating or drinking dairy products. If you have lactose intolerance, you quickly learn to avoid lactose-containing products or use lactase preparations that help digest lactose. Please note that cheeses and yoghurt are generally tolerated because the bacteria used in the culturing process to produce these dairy products break down the lactose.

We know that many bacterial overgrowth products can impact human metabolism and behaviour. For example, people with liver dysfunction can’t metabolise these bacterial toxins and they develop hepatic encephalopathy. People with neurological disorders with reduced brain and cognitive reserve tend to be more susceptible to the effects of these bacterial metabolites, which are thought to upregulate innate immunity in the nervous system. This is why I try to stress to my patients that they should manage their constipation to prevent this from happening. Severe constipation and faecal impaction should be viewed as a chronic infection and managed and treated.

Diagnosis of SIBO

A breath test is most commonly used to diagnose SIBO. This noninvasive test measures the amount of hydrogen or methane you breathe out after drinking a mixture of glucose and water. A rapid rise in exhaled hydrogen or methane indicates bacterial overgrowth in the small intestine. Although widely available, breath testing is less specific than other tests for diagnosing bacterial overgrowth.

The gold standard for diagnosing SIBO is a small intestine aspirate and fluid culture. The fluid sample is obtained as part of a small bowel endoscopy. Other tests can include abdominal X-rays or CT scans. Faecal impaction resulting from constipation can also be diagnosed from spinal MRI scans of people with MS.

Management of SIBO

The initial way to treat bacterial overgrowth is to manage the underlying bowel hypomobility problem and clear any faecal impaction. In parallel, a course of antibiotics may be needed to reduce the number of abnormal bacteria in the bowel. However, unless you deal with the underlying problems, the bacteria will repopulate the bowel when the antibiotics are discontinued. This is why some people with SIBO may require long-term antibiotics. Switching between different antibiotics helps prevent bacterial antibiotic resistance from emerging. Please be aware that antibiotics wipe out most intestinal bacteria, both normal and abnormal; hence, they are not an ideal long-term solution to SIBO.

Starting a gut health programme is an essential part of treating SIBO. You will need a nutritional review, possibly with a dietitian, and you may need to change your diet to prevent constipation and/or faecal impaction. In some cases, you may require supplements. particularly if you are vegan.

Management of faecal incontinence

Being incontinent in public is one of the most embarrassing things that can happen to someone with MS, and it may result in social isolation to avoid experiencing the embarrassment again. Many patients with MS describe their experience of being incontinent of faeces and/or urine in public as the worst thing that has happened to them. It doesn’t have to happen; there are many ways to prevent it.

Faecal urgency needs attention (as does urgency incontinence – see section on bladder disorders). It is best treated by developing a bowel routine and trying to evacuate your bowels at a regular time of day, typically in the morning. This can be aided by using something to stimulate the bowels. I usually start by prescribing glycerine suppositories or mini-enemas. If the latter fails, I may elect to use transanal irrigation.

Transanal irrigation may sound drastic, but it often makes a massive difference to the quality of life in people with MS who need it and helps them to tackle a problem that can otherwise leave them stranded at home. I regularly refer patients for assessment to use the commercial rectal irrigation system, Peristeen, mainly because of the psychological benefits they derive from it.

The biggest problem with poor rectal compliance and faecal urgency is the odd occasion when you have diarrhoea due to gastroenteritis. With diarrhoea, whatever the cause, your rectum fills multiple times during the day and hence you are more likely to be incontinent. In this situation, you may need to use incontinence pads.

Faecal incontinence is not necessarily linked to disability. Why not? The reason is that a strategically placed MS lesion in the spinal cord can impact bowel function without causing other disabilities. I have patients who have had spinal cord relapses that leave them with faecal urgency and episodes of faecal incontinence, but very little other disability.

Case example

One patient of mine developed a severe anxiety disorder following an episode of faecal incontinence in public. She had intrusive thoughts and unpleasant flashbacks, reliving the episode repeatedly. After referral to a psychiatrist, she was diagnosed as having post-traumatic stress disorder. It took several years of counselling for her to overcome the social phobia associated with her anxiety and start going out again.

She now ventures out only after having an enema to clear her lower colon and rectum; she never eats when she is out, so as not to stimulate the reflex urge to defaecate that follows eating. She wears pads and carries a change of clothing. Her faecal incontinence emergency pack contains wet wipes, clean underwear, spare continence pads and poo bags to dispose discreetly of any used items – the same items I packed when I went out with my daughters before they were potty trained.

The importance of managing bowel dysfunction

Bowel dysfunction is one of the hidden symptoms of MS. To assess whether or not you have a bowel problem, and its severity, you can complete the Wexner Incontinence Score. Over the lifetime of the disease, most people with MS develop bowel problems, so it is important to realise that much can be done to help you. Please discuss these symptoms with your neurologist or MS clinical nurse specialist. 

On the positive side, if MS is treated early and effectively before the neuronal pathways that control bowel function are damaged, these issues can usually be avoided or delayed. Preventing disability, such as bowel dysfunction, is better than treating it. This is another critical reason to manage your MS actively with DMTs.

DMTsSafety, Monitoring MS

How can I reduce my chances of adverse events on specific DMTs?

The complications associated with immunosuppression vary from DMT to DMT. You will find it helpful to understand what investigations to expect before and during treatment and how these may vary depending on the DMT(s) you are considering.

Key points

  • Numerous tests are carried out at the start of your treatment (baseline); these include blood, urine and tests for a range of infections.
  • Some patients will need tests or procedures specific to their DMT that are inappropriate for everyone with MS – for example, vaccination against some infections; pregnancy and/or genetic counselling; prevention of cardiovascular complications; and management of infusion reactions.
  • Ongoing monitoring is required for many but not all of the above factors.
  • All licensed MS DMTs have had a thorough risk ̶ benefit assessment, and their benefits are considered to outweigh the potential risks.

Standard tests … and why we do them

If you have read the article on immunosuppression, you will know that immunosuppressive DMTs may reduce white blood cell counts and antibody responses to vaccines and increase the likelihood of some infections and cancers. However, we can reduce the risk of many complications associated with long-term immunosuppression (we use the shorthand ‘de-risk’). This article explains what needs to be done at the start of DMT administration (baseline) and during subsequent monitoring. The specifics, however, vary from DMT to DMT.

Baseline tests

Tests at baseline (before starting DMT administration) include full blood count, platelets, liver, kidney and thyroid function tests, and a urine screen. Recording baseline immunoglobulin levels is particularly important if you are about to start an anti-CD20 therapy (ocrelizumab, ofatumumab or rituximab) so that we have a reference level for future comparisons. 

Serum protein electrophoresis is done for patients considering starting interferon-beta; having a so-called monoclonal gammopathy (an abnormal immunoglobulin) is a contraindication to starting an interferon-beta formulation in people with MS. The drug has been associated with a form of capillary leak syndrome, leading in rare cases to death from an adult respiratory distress syndrome.

The table below summarises the routine investigations required at baseline; subsequent sections provide further detail.

Tests routinely carried out at the start of treatment (baseline).
AHSCT, autologous haematopoietic stem cell transplantation; CMV, cytomegalovirus; CSF, cerebrospinal fluid; DMT, disease-modifying therapy; EBV, Epstein ̶ Barr virus; ECG, electrocardiogram; FBC, full blood count; HIV, human immunodeficiency virus; HPV, human papillomavirus; JCV, JC virus; LFTs, liver function tests; MMR, measles/mumps/rubella; MRI, magnetic resonance imaging; PCP, pneumocystis pneumonia; PML, progressive multifocal leukoencephalopathy; TB ELISpot, tuberculosis enzyme-linked immune absorbent spot; TFTs, thyroid function tests; U&E, urea and electrolytes; VZV, varicella zoster virus.

Infection screening

At our centre, we screen for a relatively large number of infectious diseases so that we can treat any subclinical infection before starting a DMT. This is particularly relevant for HIV-1 and 2, hepatitis B and C, syphilis and tuberculosis (TB).  

Screening for the JC virus (JCV), which causes progressive multifocal leukoencephalopathy (PML), is only really needed for people with MS considering starting natalizumab. Even if you are JCV positive, you can be treated with natalizumab for 6 ̶ 12 months and sometimes longer if you are prepared to take on the risk of PML and the extra monitoring required to detect PML early. 

We only check measles/mumps/rubella (MMR) status in patients without documentation of full vaccination as children. We check varicella zoster virus (VZV) status before starting immunosuppression and vaccinate seronegative individuals. Currently, we are still using the live VZV vaccine. This will change, and we will likely be offering all people with MS in the UK the component inactive VZV vaccine (Shingrix, that has had its licence extended) to reduce the chances of zoster reactivation in all adults starting immunosuppression. This new Shingrix indication is similar to the pneumococcal vaccine (Pneumovax). Our centre is only recommending Pneumovax in patients about to start an anti-CD20. However, when Shingrix becomes available on the NHS, it will make sense to bundle this with the Pneumovax and make it routine for all people with MS before starting immunosuppressive therapy. Please check with your healthcare team which products are available locally.

Routine tests and monitoring for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are only needed for subjects undergoing autologous haematopoietic stem cell transplantation (AHSCT), which causes profound short-term immunosuppression that can result in CMV and EBV reactivation. CMV reactivation also occurs with alemtuzumab, so this needs to be considered when investigating patients who develop complications after receiving alemtuzumab (please see Opportunistic infection in MS). 

For patients starting long-term immunosuppression, it is advisable to screen for active human papillomavirus (HPV) infection (by cervical smear or vaginal swab) and for warts or active infection with molluscum contagiosum. Warts are caused by HPV skin infection; molluscum contagiosum is due to a relatively benign pox virus that typically affects young children but occasionally affects adults. Warts and molluscum contagiosum can spread rapidly in patients receiving alemtuzumab, so I recommend treating these skin infections before starting immunosuppression for MS. 

Vaccinations

We encourage all patients to be vaccinated against COVID-19 and seasonal flu; outside the flu vaccine season, we remind people to get vaccinated during the next vaccine season. 

Hepatitis B, meningococcal and Haemophilus influenzae vaccines are considered only for people with MS who are at high risk of infection and have not had these vaccines as part of a national vaccine programme, i.e. healthcare and laboratory workers for hepatitis B, school and university students and military recruits for meningococcal vaccine and paediatric patients for Haemophilus influenzae. 

The issue around having the HPV vaccine as an adult is more complex. For example, in the UK, the NHS does not cover the cost of the vaccine for people over 25. In addition, most people have only had the quadrivalent vaccine (Gardasil-4), which covers about two-thirds of the strains that cause cancer. Some people with MS may want to upgrade their immunity with the polyvalent vaccine (Gardasil-9) that covers over 95% of the cancer-causing strains of HPV. For more information on HPV vaccination, please see Case study: cervical intraepithelial neoplasia (CIN) and ocrelizumab.

MMR is a live vaccine given in childhood (see MMR vaccine: to vaccinate or not? ). Owing to vaccine hesitancy, however, many people do not receive this vaccine as children. Therefore, if an adult with MS is about to start immunosuppressive therapy and has not been vaccinated against MMR, we advise them to do so. This is particularly important for people about to start natalizumab because these viruses are neurotropic and can infect the brain. Natalizumab blocks immune response within the brain; hence, exposure to a neurotropic virus could cause serious infection, similar to what we see with the JC virus – which causes PML.

Travel vaccines for people who travel as part of their work or plan to travel shortly need to be considered. In particular, the yellow fever vaccine is a live vaccine (made from a weakened yellow fever virus strain) and it should ideally be given before someone starts on immunosuppressive therapy. 

Cardiovascular screening

You may need an ECG (electrocardiogram), to rule out an abnormal heart rhythm or electrical conduction abnormality and to check your left ventricular function (ejection fraction). These abnormalities are a relative contraindication to using the S1P modulators (fingolimod, siponimod, ozanimod, ponesimod), which may affect the conduction of the heart. In patients treated with mitoxantrone, the left ventricular ejection fraction (LVEF) must be done at baseline and regularly monitored because mitoxantrone is toxic to the heart. If the LVEF drops significantly, further dosing of mitoxantrone is contraindicated. 

Pregnancy, family planning and genetic testing

Many chemotherapy agents used in AHSCT for ablating (extracting) the bone marrow are toxic to the ovaries and testes. Therefore, patients receive counselling before treatment and can have eggs (oocytes) or sperm banked for future use. Egg banking is also a consideration for women with MS being treated with mitoxantrone. Men receiving mitoxantrone do not need to bank sperm, however, because mitoxantrone does not cross the testes ̶ blood barrier. 

Genetic testing is only required at present if you wish to receive siponimod. Siponimod is metabolised by a specific liver enzyme (biological catalyst) with two functional variants – slow metabolising and fast metabolising. People who carry two slow-metabolising variants of the enzyme cannot receive siponimod. Intermediate metabolisers (those that carry one slow- and one fast-metabolising version of the enzyme) receive low-dose siponimod, while those with two fast-metabolising enzymes receive high-dose siponimod. 

Protecting against progressive multifocal leukoencephalopathy

I have included magnetic resonance imaging (MRI) and lumbar puncture with cerebrospinal fluid (CSF) testing for JCV among the baseline tests. This is specific to patients at high risk of developing PML who are switching from natalizumab to a depleting immune reconstitution therapy such as alemtuzumab or another therapy that depletes their immune system (e.g. cladribine or an anti-CD20 therapy). These tests are done to exclude asymptomatic PML, which will otherwise be carried over to the new treatment. The effects of these immunosuppressive therapies on your immune system cannot be rapidly reversed, which is a problem because immune reconstitution is needed to clear PML. Most MS centres do not mandate CSF testing in this situation because it does not always reveal the presence of PML. However, I still request this test on my patients to gain as much information as possible on which to base potentially life-changing decisions.

Prophylactic antivirals and antibiotics

Patients in our centre undergoing AHSCT or receiving alemtuzumab will be given antivirals and antibiotics to reduce the likelihood of certain infections. This is particularly relevant for listeriosis, which is a rare infection transmitted via food. We also encourage all our patients to start and maintain a specific diet to reduce the chances of listeriosis. The risk of listeriosis is only present for a short period when both the adaptive and innate immune systems are compromised, that is, for 4 weeks after receiving alemtuzumab, so we recommend antibiotic prophylaxis for 4 weeks. Our online resource provides more information about listeriosis. If you live in the UK, you can order our free listeriosis prevention kit, which contains a booklet (also downloadable) and various practical items to help keep you safe.

Strategies for limiting the risks from immune reconstitution therapies and infusion DMTs.

Infusion reactions

When you use agents that cause cell lysis (breakdown), such as alemtuzumab and intravenous anti-CD20 therapies, the contents of cells cause infusion reactions. To prevent such reactions or reduce their severity, we pretreat patients with corticosteroids, antihistamines and antipyretics. The exact protocols for each DMT differ; for example, ocrelizumab infusion reactions are generally only a problem with the first and second doses; therefore, many centres don’t give steroids with the third and subsequent infusions. The latter was particularly important during the COVID-19 pandemic when it was shown that the recent administration of high-dose steroids increased your chances of severe COVID-19. 

Ongoing monitoring

Once someone has been treated with a DMT, ongoing monitoring is required. What gets monitored and how frequently depends on the individual DMT. For a list of DMTs associated with important adverse events, please see our summary Table in ‘De-risking’ guide: monitoring requirements of individual DMTs.

The regulatory authorities usually put in place specific monitoring requirements, which can differ worldwide. It is important that you also enrol in your national cancer screening programmes. Being on chronic immunosuppression increases your chances of developing secondary malignancies, so please remain vigilant. 

Tests carried out regularly as part of ongoing monitoring.
FBC, full blood count; LFTs, liver function tests; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy; TFTs, thyroid function tests; U&E, urea and electrolytes.

I want to reassure you that all licensed MS DMTs have undergone a thorough risk ̶ benefit assessment by the drug regulators, and the benefits of these treatments are considered to outweigh the potential risks. On balance, the level of immunosuppression associated with MS DMTs is typically mild to moderate; hence, the complications are relatively uncommon. MS is a serious disease and, if left to run its natural course, would result in most patients becoming disabled. To learn more about the natural course of MS, please read the section entitled What are the consequences of not treating MS?

DMTsSafety, Monitoring MS

‘De-risking’ guide: monitoring requirements of individual DMTs

Before you start taking a disease-modifying therapy (DMT), your MS team will carry out routine tests and investigations, many of which are repeated during subsequent monitoring or before switching to another DMT. The regulatory authorities that license the drugs specify their monitoring requirements. What gets monitored and how frequently depends on the individual DMT.

All licensed MS DMTs have undergone a thorough risk ̶ benefit assessment by the drug regulators, and the benefits of these treatments are considered to outweigh the potential risks. The table below summarises the main monitoring requirements of individual DMTs or DMT classes. For more detailed information, see the post on reducing your chances of adverse events.

AHSCT, autologous haematopoietic stem cell transplantation; CMV, cytomegalovirus; CSF, cerebrospinal fluid; EBV, Epstein ̶ Barr virus; ECG, electrocardiogram; HPV, human papillomavirus; JCV, JC virus; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy.