© 2019 by Mark Street.

Treatment //

Treatment of vasculitis often invloves two (2) phases, namely induction whereby medication is prescribed in order to reduce the inflammation and suppress the immune system; and maintenance in order to control and/or sustain remission of the disease. Some patients experience remission for many years with little or no manifestation of disease activity. In others, some of the signs and symptoms are not completely eliminated and therefore required to be controlled.

The most common prescription medications are:

  • Corticosteroids: Corticosteroids, such as prednisolone and its variants, are prescribed in the control of chemicals (cytokines) released by the immune cells of the body. It is partly these cytokines that cause inflammation in the body, in response to foreign bodies (such as viruses, bacteria, environmental chemicals) or in certain circumstances self bodies (autoimmune diseases such as vasculitis). 

      Possible side effects include weight gain, diabetes and bone thinning (osteoporosis). If a corticosteroid is needed for long-term (maintenance)               therapy, you'll likely receive the lowest dose possible.

  • Methotrexate (Methoblastin): Methotrexate is known as a disease-modifying drug. It is often used for the treatment of rheumatoid arthritis and now other autoimmune diseases. Its mechanism of action is by inhibiting enzymes released by immune cells in the body and thereby resulting in reduced inflammatory responses. 

    • The most common side effects of methotrexate include nausea or vomiting and abnormalities in liver function tests. Liver function tests are blood tests your doctor may order to watch your liver. These side effects are more likely to occur at higher doses. About 1-3 percent of patients develop mouth sores (called stomatitis), rash, diarrhea, and abnormalities in blood counts. Methotrexate may cause cirrhosis (scarring) of the liver, but this side effect is rare and most likely to occur in patients who already have liver problems or are taking other drugs that are toxic to the liver.

    • Lung problems (persistent cough or unexplained shortness of breath) can occur rarely when taking methotrexate. These side effects are more common in people with poor lung function. Persistent cough or shortness of breath should be reported to your doctor.

    • Slow hair loss is seen in some patients, but hair grows back when the person stops taking this medication. This can often be managed by taking a folic acid vitamin with methotrexate. Methotrexate can increase the sensitivity of the skin to sunlight, so limiting sun exposure and the use of sunscreen is advised. The use of folate supplements (folic and folinic acid) often are given with methotrexate. These are B vitamins and can decrease most side effects during methotrexate treatment.

    • It is important to remember that most patients do not experience side effects, and that, for those who do, many of the minor side effects will improve with time. Methotrexate treatment should be discontinued for at least three months before attempting to become pregnant. Even though methotrexate should not be taken during pregnancy, it does not reduce a woman’s chance of becoming pregnant in the future. Men taking methotrexate should talk to their physician prior to attempts to conceive.

Source http://www.rheumatology.org

  • Azathioprine (Azamun, Azapin, Imuran, Thioprine): Azathioprine is a drug that is used for conditions such as rheumatoid arthritis, lupus, and vasculitis diseases. Its mode of action is by interfering with cell DNA synthesis and thereby inhibiting certain cell production (such as white blood cells). 

    • The most common side effects of azathioprine can involve the gastrointestinal tract (which includes the stomach, intestines, liver and pancreas) and the blood cells. Approximately 10­­­­­­­-15 percent of patients may have nausea and vomiting after taking this medication, sometimes accompanied by abdominal pain or diarrhea. Taking the medication twice daily instead of all at once, or taking it after eating, may help avoid these problems. If vomiting occurs, you should contact your doctor, as this may be a sign of a serious reaction.

    • Less often, azathioprine may cause hepatitis (liver swelling or damage), pancreatitis (swelling or damage to the pancreas gland behind the stomach, which can cause abdominal pain) or an allergic reaction that may include a flu-like illness or a rash. Azathioprine also can lower the number of infection-fighting white blood cells. 

    • Before or during treatment, your doctor may perform a thiopurine methyltransferase enzyme activity level (TPMT). This enzyme helps clear the medication from your system. If you have lower amounts of these enzymes, you may be at higher risk for medication toxicity.

    • Long-term use of azathioprine in combination with other immune-suppressing medications in transplant patients has been associated with a slightly elevated risk of cancer. There may be a slight increased risk of lymphoma (a form of cancer) in patients taking this medication for inflammatory bowel disease.  This risk appears to be increased when taken along with medications known as anti-TNF drugs (or TNF inhibitors) in the treatment of Crohn’s disease or ulcertative colitis. It is not clear whether arthritis patients face a similar risk.

- Source: http://www.rheumatology.org

  • Mycophenolate Mofetil (CellCept) and Mycophenolate Sodium (Myfortic): Originally used in patients undergoing organ transplants for the suppression of the immune system to mitigate tissue rejection, it is currently also used in autoimmune diseases such as vasculitis. Its mode of action is by interfering with cell DNA synthesis and thereby suppressing the immune system. 

    • The most common side effects with mycophenolate include upset stomach, nausea, vomiting or diarrhea. The frequency of these side effects may depend on the form of mycophenolate (e.g. mycophenolate mofetil (CellCept) or the delayed release mycophenolate sodium preparation, Myfortic) being used. Other possible side effects include headache, dizziness, difficulty sleeping, tremor and, occasionally, rash. These side effects usually go away with time, but tell a doctor if they persist.

    • Less common but more serious side effects include swelling in legs or face, elevated blood pressure, a reduction of white blood cells (increasing the chances of infections, including viral infections such as herpes zoster (“shingles”), red blood cells that bring oxygen to tissues (which may lead to anemia), and platelets that aid clotting (which can lead to gastrointestinal bleeding or dark tarry stools)). Periodic blood tests can detect reduced blood counts early on to avoid these problems.

    • Serious infections can occur while taking mycophenolate, such as bacterial infections (e.g. endocarditis or meningitis), tuberculosis, fungal infections, viral infections and reactivation of certain kinds of viral infection such as herpes zoster (shingles), hepatitis B or C reactivation, or a rare life threatening neurologic condition called progressive multifocal leukoencephalopathy (PML) as a result of reactivation of past viral exposure.

    • Patients older than 65 may be at increased risk for some side effects, especially infections and gastrointestinal bleeding. People who have had ulcers or other serious gastrointestinal conditions should talk with their doctors before taking this medication.

    • Studies of transplant patients taking mycophenolate have found it may increase risk of some cancers such as lymphomas and skin cancers. Because there may be a similar risk in people with rheumatic conditions who take mycophenolate for long periods of time, discuss this issue with a physician before starting the medication. When on mycophenolate, it is important to see a physician regularly, use a sunscreen and avoid prolonged sun exposure.

- Source: http://www.rheumatology.org

  • Cyclophosphamide (Cyclobastin, Endoxan): Cyclophosphamide was initially used for untreatable rheumatoid arthritis and later autoimmune diseases such as vasculitis. It is known as an alkylating agent and inhibits cell DNA synthesis and therefore cell death of certain cells (such as white blood cells). Cyclophosphamide is usually reserved for severe disease activity with vital organ involvement due to its toxicity. 

    • Common side effects, which may be worse with the pills, include nausea and vomiting. These symptoms usually can be controlled with anti-nausea medications. Hair loss can occur, but hair usually will grow back when the medication is stopped. Other common side effects include skin rashes. Cyclophosphamide increases the risk of developing some kinds of infections, especially herpes zoster, often referred to as “shingles.” Unusual infections can occur with cyclophosphamide use. Other important side effects include:

    • Blood cells: Cyclophosphamide can have significant effects on the blood cells, typically causing a reduced number of white blood cells, a key component of the body's immune system. This can occur 8-12 days after starting treatment. Your doctor will check your blood counts around this time and make dose adjustments as needed.

    • Fertility problems: Cyclophosphamide can cause infertility in both men and women. This often is seen in older patients or those taking higher doses for long periods of time. Discuss this issue with your doctor before taking cyclophosphamide. Although women taking cyclophosphamide can stop having periods, they can still become pregnant so an effective form of birth control to prevent pregnancy should be used while taking this medication. Taking cyclophosphamide during pregnancy is very dangerous to an unborn child. 

    • Bladder problems: Cyclophosphamide is broken down in the body into several other products. One byproduct known as acrolein can cause an irritation of the bladder, or “cystitis,” which may result in blood in the urine or scarring of the bladder. Patients taking oral cyclophosphamide should drink plenty of fluids each day to help prevent problems. Discuss with your doctor how much fluid you should consume daily while on cyclophosphamide.  Patients receiving intravenous therapy are sometimes given a medication called mesna (Mesnex) to help prevent bladder problems.

    • Cancers: Cyclophosphamide increases the risk of developing some kinds of cancers, which can occur years after taking this medication.  Long-term use and higher doses of cyclophosphamide may lead to a higher risk. Bladder cancer is the most common cancer related to cyclophosphamide, so your doctor will recommend periodic urine tests to screen for this.  This needs to be continued for many years, even if your disease is in remission.

- Source: http://www.rheumatology.org/ and Chighizola, C; Ong; V H, Denton, C (2011):Cyclophosphamide as Disease-modifying Therapy for Scleroderma. Int J Clin Rheumatol. 6(2):219-230. 

  • Rituximab (Rituxin, MabThera): Rituximab is a biological medicine that has been developed initially for rheumatoid arthritis patients and later demonstrated to be efficacious in the treatment of certain vasculitic diseases, such as GPA, MPA and EGPA. Rituximab is a chimeric (human and animal) antibody that binds to a glycoprotein (CD20) which is expressed on b cells (Refer to The Immune system). The result is cell death (apoptosis) of the b cells and therefore loss of ANCA antibodies. Click on the video to watch a demonstration of rituximab's mechanism of action. 


      There has been, and continues to be a number of clinical trials to determine the safety and efficacy of rituximab versus cyclophosphamide (RAVE         studies) and rituximab versus azathioprine. The outcomes so far indicate good safety and comparative efficacy to these conventional drugs.

Some patients feel mild side effects during or up to 24 hours after receiving rituximab. These usually occur with the first infusion, and can include mild throat tightening, flu-like symptoms, rash, itchiness, dizziness and back pain. These symptoms can be reduced by receiving a steroid injection before the infusion, along with acetaminophen (Tylenol) and diphenhydramine (Benadryl). The infusion is sometimes stopped for a short while and then restarted at a slower rate if the symptoms get better. Rarely, patients will have more serious symptoms, such as wheezing, mouth or throat swelling, trouble breathing or chest pain. Patients who experience these symptoms should tell their health care providers immediately; patients may receive stronger medications to treat those symptoms.

Other side effects around the time of the infusion can include headache, cough, nausea, upset stomach, sweating, nervousness, muscle stiffness, and numbness. Patients can take mild pain medications, such as acetaminophen, for them, but should call their doctors if the symptoms are severe or get worse.

In the months after the treatment, some people may notice more frequent infections, such as colds or sinusitis. Usually, these are not severe. There are a few rare but serious side effects from rituximab. These include severe skin reactions and mouth sores. Patients who experience vision changes, loss of balance, difficulty walking or confusion should contact their doctors immediately.

- Source: http://www.rheumatology.org

There is ongoing research into other drugs for the treatment of autoimmune diseases, and in particular vasculitis. These include drugs that target complement C5 of the immune system, T cells and other b cell targets.



Video // (Rituximab mode of action)

Source:Sarmad, Jamal (2014): Mechanism of Rituximab.

Further information on these drugs may be found in the Resources section produced by the Australian Rheumatology Association.