Steroids and Immunosuppressants
Both Prednisolone (steroids) and Immunosuppressants such as Cyclophosphamide, Azathioprine, Methotrexate and Mycophenolate Mofetil reduce inflammation by suppressing the activity of the white blood cells. However, by doing this these white blood cells are less able to fight infection. The immunosuppressants can also suppress the production of cells from the bone marrow.
Vasculitis UK recommends the following website for information about cortisone (steroids) and corticosteroid therapies: Cortisone-info – contains a wealth of information from side effects, to steroid reduction and everything between.
(See below for more on Steroids, Cyclophosphamide, Azathioprine, Methotrexate and Mycophenolate Mofetil)
List of drugs and side effects used in the treatment of vasculitis
The following is a list of many of the drugs used to treat and maintain remission in the various vasculitides. Some of the drugs mentioned are prophylactic (prescribed to prevent disease). A number of the drugs are general to many of the vasculitides whilst others are specific to individual vasculitic diseases.
The list is not exhaustive and new drugs are constantly being developed. The lists of side effects is not exhaustive and patients are encouraged to read the information sheets supplied with prescription medication and to discuss any concerns with their medical team.
Adalimumab (Humira)
An artificial manufactured antibody that can be injected to reduce the effect of tumour necrosis factor alpha (TNF). TNF is an important protein in the body that can cause inflammation and is important in fighting infection. Immediate side effects are unusual but can include: mouth ulceration, diarrhoea, cough, dizziness, fatigue, paraesthesia (tingling of the skin), musculoskeletal pain, rash and pruritus (itching). A major side effect can be a reduced ability to fight some types of infection and possibly to control cancer cells in the body.
Antihistamines
Used to treat allergies and itching. Sedating antihistamines may initially cause sleepiness. Non-sedating antihistamines rarely cause drowsiness.
Briefing by Prof David Jayne, University of Cambridge, June 2024
Avacopan (Tavneos)
What is avacopan?
Avacopan is a drug with the trade name Tavneos, developed for the treatment of ANCA associated vasculitis (AAV) by an American Company, Chemocentryx, and is the first drug ever to be successfully developed just for AAV. Other drugs we use in AAV have been repurposed from more common diseases. Avacopan is marketed in the UK by CSL Vifor and comes as a 10mg orange/yellow hard capsule and the recommended dose is three capsules (30mg) twice a day. It is typically given for one year.
How does it work?
Avacopan interferes with the complement pathway. This is a system of proteins that start or amplify immune responses and has been developed in nature to protect us from or help us to fight infections. But the complement pathway is also engaged when the immune system misbehaves which is what happens in AAV. More specifically, avacopan blocks a key complement component, C5a, from binding to its receptor, C5aR1. C5a is important in vasculitis because it attracts white blood cells to sites of vasculitis and, along with ANCA antibodies, causes them to attack the lining of blood vessels damaging the vessel wall and causing vasculitis.
How has avacopan been tested in AAV?
After proving safe when given to healthy volunteers, avacopan was tested in two initial studies. The first study, CLEAR, was conducted in Europe and demonstrated that avacopan could potentially replace steroids in the treatment of AAV. In the second study, CLASSIC, conducted in North America, different doses of avacopan were added to standard treatments and shown to be safe. On the basis of these promising results a larger study, ADVOCATE, of 330 patients was conducted in many countries which showed that not only could avacopan replace steroids, but there were some particular advantages with avacopan. These were a reduced rate of disease relapse, fewer steroid side-effects, better recovery of patients’ quality of life, and better recovery of kidney function for those with kidney involvement. However, avacopan did not increase the chances of remission after six months and 30% of patients given avacopan either did not reach remission or required more steroid.
Can avacopan be used in the UK?
The National Institute of Clinical Excellence (NICE) evaluated avacopan in 2021 and recommended its use. Subsequently NHS England have published a commissioning policy and avacopan has been available in England and the devolved nations from 2022. It is an expensive drug and NHS England have imposed some limitations on its use, such as, who can prescribe it and the need for review by more than one doctor in a multi-disciplinary team.
Which patients should have avacopan?
The recommendation from the Medicines Regulatory agency (MHRA) and NICE is that avacopan can be used for the treatment of patients with severe, active GPA or MPA in combination with either rituximab or cyclophosphamide. In practice, this definition applies to most new and relapsing patients with GPA or MPA. There is now a debate as to which patients within this definition should have avacopan and which ones should not. Many patients will do well without avacopan but there are three groups of patients where avacopan is more likely to be helpful. The first is patients in whom steroids are going to be a particular problem, such as those with diabetes, obesity or mental health concerns; the second is those with kidney involvement that has affected their kidney function; and the third is patients whose disease has not responded well to standard treatments.
Is avacopan safe?
Avacopan is a new drug and the number of patients that have received avacopan in clinical trials is 239, which is quite small. There did not appear to be an increase in infections with avacopan, but the avacopan patients benefitted from having less steroid. There were slightly more patients on avacopan compared to those that did not who had changes in liver function and white blood cell counts. These were usually mild and reversed when avacopan was stopped. A registry has been set up in Europe, AVACOSTAR, which is collecting data on safety and will provide important safety reports in the future.
Conclusions
It is exciting to have a new drug for AAV, when patients currently have a limited choice of drugs that have been shown to work. The successful avacopan program has demonstrated how important the complement pathway is in vasculitis and will encourage more drugs to be developed for AAV which will be good for patients. There remain many answered questions about how to use avacopan and quite how safe it is, which we hope will be answered by further research.
Read about one patient’s experience with avacopan: Jane’s Story
Azathioprine (Imuran)
An important and very commonly used immunosuppressant. Major side effects are unusual but blood tests must be monitored frequently when it is started or the dose is increased because there is a risk of liver toxicity and bone marrow suppression (low white cell count and anaemia). Other side effects include fatigue, hair loss, diarrhoea, and increased risk of infection.
Bactrim (see Co-trimoxazole)
Bisphosphonates (including Zolidronic acid, Risedronate and others)
A major side effect of long term prednisolone use is osteoporosis. Bisphosphonates may be prescribed to strengthen bones and help prevent osteoporosis. Side effects from oral bisphosphonates are usually mild but include nausea, dyspepsia, diarrhoea or constipation and headaches. They cannot be used in patients with marked kidney damage.
Cellcept (see Mycophenolate Mofetil)
Ciclosporin
An immunosuppressant which works by reducing the function of lymphocytes (a type of white cell). In the long term it can cause chronic damage to the kidneys and this should be carefully monitored. In high doses it can cause reversible problems to the kidney or liver function and cause paraesthesia (tingling in hands and feet), fatigue and headache.
Colchicine
Colchicine is an anti-inflammatory drug commonly used to treat attacks of gout. It is also sometimes used to treat some forms of vasculitis such as Behcet’s disease and hypersensitivity vasculitis. It is usually given in a tablet form and often only for short periods. Common side effects are nausea, vomiting and abdominal pain. Patients with impaired kidney function may not be able to remove the drug properly from the body and short courses only should be prescribed. It rarely causes damage to kidneys, liver, nerves and muscles. Long term use should only be under expert supervision.
Cortisone (see Steroids)
Co-trimoxazole or Septrin (Bactrim)
An antibiotic prescribed to some patients being treated with high doses of immunosupression to prevent the lung infection pneumocystis carinii (also known as pneumocystis jerovicii) pneumonia. It is also sometimes used in patients with Wegener’s granulomatosis (granulomatosis with polyangiitis) as it may reduce the risk of relapse in some patients. Side effects include: nausea, diarrhoea, headache, rash and rarely a low white cell count
Cox 2 inhibitors (See Non-steroidal anti-inflammatory drugs)
Cyclophosphamide
Cyclophosphamide is commonly used to treat severe forms of vasculitis and is also widely known as an anti-cancer chemotherapy drug. It is usually given as either a daily tablet or intermittent infusion every few weeks.
Cyclophosphamide has the potential to cause serious short term side effects including bladder irritation (cystitis) and bone marrow suppression (low white cell count) leading to infection. Mesna (a uroprotectant) is often given to patients receiving injections of cyclophosphamide to reduce the risk of bladder problems. Patients may also be advised to drink a lot of water to flush out the bladder but this should be discussed with the medical team. Other short term effects include nausea and vomiting and hair loss.
Over a longer period of time cyclophosphamide can cause infertility in both men and women. Men who may still want to have children should consider sperm banking.
Long term use of cyclophosphamide is considered undesirable and has been linked to an increased risk of some types of cancer, eg cancer of the bladder.
Cytoxan (see Cyclophosphamide)
Dapsone
An antibiotic which is sometimes used to control vasculitis limited to the skin (neutrophilic dermatoses). It can cause nausea, dizziness, headache and insomnia.
Dexamethasone (See Steroids)
Etanercept
An artificial manufactured protein that can be injected to reduce the effect of tumour necrosis factor alpha (TNF). TNF is an important protein in the body that can cause inflammation and is important in fighting infection. Immediate side effects are unusual but can include: dyspnoea (shortness of breath), confusion, paraesthesia (tingling of the skin) and vertigo. A major side effect can be a reduced ability to fight some types of infection and possibly to control cancer cells in the body.
Humira (see Adalimumab)
Immunoglobulin
Normal human immunoglobulin is sometimes used to treat some forms of vasculitis, often when other treatments cannot be tolerated or have been ineffective. It is a particularly important treatment in Kawasaki’s Disease. It is given as an intravenous infusion and repeated infusions may be necessary. Side effects are common during or following each infusion including nausea, diarrhoea, chills, fever, headache, dizziness, joint, muscle and back pains. Rarely serious allergic reactions or kidney failure may occur.
Imuran (See Azathioprine)
Infliximab
An artificial manufactured antibody that can be injected to reduce the effect of tumour necrosis factor alpha (TNF). TNF is an important protein in the body that can cause inflammation and is important in fighting infection. Immediate side effects are unusual but can include: diarrhoea, flushing, chest pain, dyspnoea (shortness of breath), dizziness and fatigue. A major side effect can be a reduced ability to fight some types of infection and possibly to control cancer cells in the body.
Lansoprazole
Used to treat and prevent damage cause by the use of NSAIDs. (see NSAIDs)
Losec (see Omeprazole)
Mesna
Mesna is an “uroprotectant” used to prevent bladder damage during intermittent cyclophosphamide treatment. Side effects include: nausea, diarrhoea, headache, rash and dizziness.
Methotrexate
An important and very commonly used immunosuppressant. Major side effects are unusual but blood tests must be monitored frequently when it is started or the dose is increased because there is a risk of liver toxicity and bone marrow suppression (low white cell count and anaemia). Patients should also be aware that methotrexate can cause short and long term lung damage which should be monitored. Other side effects include: gastro intestinal (GI) upset, dyspepsia (indigestion), dizziness, fatigue, chills, headaches and mood changes.
Methylprednisolone (See Steroids)
Monoclonal antibodies
These include Adalimumab (Humira), Infliximab and Rituximab
Mycophenolate Mofetil (Cellcept) and Mycophenolic acid (Myfortic)
An important and relatively commonly used immunosuppressant. Major side effects are unusual but blood tests must be monitored frequently when it is started or the dose is increased because there is a risk of bone marrow suppression (low white cell count and anaemia). Side effects include: diarrhoea, vomiting, dyspnoea (shortness of breath), insomnia, skin irritation and flu like symptoms. Stomach and bowel side effects are relatively common.
Mycophenolic acid (see Mycophenolate Mofetil)
Myfortic (see Mycophenolate Mofetil)
Non-steroidal anti-inflammatory drugs (NSAIDs) and Cox 2 inhibitors
These groups of drugs includes ibuprofen, diclofenac (voltarol) indomethacin, celecoxib and etoricoxib. They are commonly prescribed for the control of pain, especially joint pain and can be very effective. Some of them are available without prescription. They should be used with caution as they commonly have side effects and can interfere with other prescribed medication. Even the drugs available without prescription can cause problems and patients should discuss with their medical team before taking them.
Side effects are common with these drugs. Serious side effects include the risk of stomach ulcers and bleeding ulcers, an increase in the overall risk of bleeding and an increase in the risk of heart attacks and strokes.These drugs can also cause serious problems for patients with any kidney disease and they should not be taken by patients with kidney problems without careful discussion with the medical team. They should not be taken by patients with a history of stomach ulcers. They can also cause problems with fluid retention and high blood pressure.
NSAIDs (see Non-steroidal anti-inflammatory drugs)
Omeprazole
Used to treat and protect damage caused by the use of NSAIDs (see NSAIDs)
Prednisolone (see Steroids)
Prednisone (see Steroids)
Ranitidine
Used to treat and prevent damage caused be the use of NSAIDs. (see NSAIDs)
Risedronate (see Bisphosphonates)
Rituximab
A manufactured artificial antibody which removes B-cells (a type of white cell). It is now increasingly being used in patients as an alternative to cyclophosphamide and other immunosuppressants in the types of vasculitis where B cells and the antibodies they produce are thought to be important. Side effects are generally mild and are infusion related – occurring during or up to 2 hours after infusion. Side effects include: rashes and gastro intestinal (GI) upset.
Septrin (see Co-trimoxazole)
Steroids (Prednisolone, Methylprednisolone, Cortisone, Prednisone, Dexamethasone)
Steroids are naturally occurring hormones produced in the body by the adrenal glands and are essential for normal health.Artificial steroids are commonly used to treat vasculitis and other inflammatory diseases and are very effective at reducing inflammation. They are often used initially at high doses to control the disease and then the dose will be reduced as quickly as is possible to reduce the side effects.
Unfortunately side effects are very common with steroid medication. Common serious side effects include increased risk of infection, diabetes and osteoporosis. Other common side effects include weight gain, disturbed sleep, altered mood (including rarely depression and very rarely psychosis), muscle weakness, dyspepsia (indigestion) and stomach ulcers, increased hair growth, fluid retention, increased blood pressure and thin skin.
When artificial steroids are being taken the adrenal glands may stop producing the body’s own steroids so it is essential that the patient does not stop taking steroids suddenly and the rate of reduction must be closely monitored by the physician. Stopping steroids too quickly can result in steroid deficiency if the adrenal glands are unable to respond quickly and this can cause significant problems.
It is essential that patients on high dose steroids are monitored for the development of diabetes. If appropriate, patients may be prescribed bisphosphonates, calcium or vitamin D to protect their bones. Patients may also be prescribed tablets to protect the stomach from side effects (eg. Ranitidine, Lansoprazole, Omeprazole or similar).
Further indepth information on steroids, for patients and their family, is available at: Cortisone Information
Tacrolimus – Similar to Ciclosporin
An immunosuppressant which works by reducing the function of lymphocytes (a type of white cell). Side effects can include: headache, diarrhoea, nausea, blurred vision and constipation.