How Does Methotrexate Work For Rheumatoid Arthritis

Methotrexates Possible Side Effects

So what are methotrexates possible side effects? The most common negative effects associated with this particular medication are gastrointestinal symptoms like nausea, vomiting, and ulcers . Some doctors have also reported that patients have developed mouth sores, fatigue, headache, dizziness, or shortness of breath. It may cause hair loss as well.

Though the risk is small, methotrexate therapy can also cause liver damage, so patients who take the medication on a regular basis as a form of RA treatment need to have routine blood tests taken by their doctor to make sure their liver remains healthy. To reduce any further risk of liver damage, patients taking methotrexate should also avoid drinking alcohol. If damage is suspected, your doctor may request a liver biopsy.

In a few rare cases, methotrexate has been known to cause lung inflammation or a decrease in white blood cells or platelets, a condition which can lead to bone marrow suppression. According to University of Pittsburg Medical Center , bone marrow suppression occurs when the marrow doesnt make the normal amount of blood cells.

Ultimately, this can instigate other medical conditions such as anemia, leukopenia, neutropenia, or thrombocytopenia says the UPMC. By limiting the likelihood of bone marrow suppression then, youre also reducing your risks of these other conditions. Fortunately, routine blood testing by your doctor can identify these potential issues so they can be stopped before they progress.

How Do I Take Methotrexate

Methotrexate is typically taken once a week for RA. It is available as both a tablet you take by mouth and as an injection. With the tablets, most people start with one 7.5 mg dose once a week, but your provider may recommend up to a maximum dose of 25 mg once a week depending on how you respond. To reduce the risk of side effects, they may ask you to split the dose into smaller doses that you take throughout the day of the week youre scheduled to take your medication.

If youre using the injection, thats once a week, too. Youll inject the medication either into your muscle or right under your skin, depending on what your provider recommends. The injection is available as either an auto-injector or as a vial. You can find instructions on how to use Rasuvo from the manufacturer here.

What Are The Possible Side Effects Of Methotrexate

Common side effects associated with methotrexate include4:

• Dizziness
• Swelling and/or tenderness of gums and mouth sores
• Sun sensitivity

In some patients, methotrexate can cause serious side effects. These include blurred vision or a sudden loss of vision, confusion, loss of consciousness, seizures, and weakness or difficulty moving one side of your body. If you experience any of these side effects or any other unusual problems while you are taking methotrexate, call your doctor immediately.

This is not an exhaustive list of all potential side effects of methotrexate. For more information, consult your doctor or healthcare provider. If you notice any new or worsening side effects, contact your doctor or healthcare provider immediately.4 For more information on adverse effects, see the FDA black box warning for methotrexate.

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When Patients Cant Tolerate Methotrexate

When patients can’t tolerate methotrexate, it puts doctors in a conundrum, says Dr. Jeffrey Curtis of the University of Alabama in this Q& A.

Methotrexate is the gold-standard treatment for rheumatoid arthritis. But only about 30 percent of patients achieve low disease activity or remission on methotrexate alone. Of the remaining 70 percent, some can’t tolerate the drug at all because of side effects like mouth ulcers, nausea and vomiting and hair loss.

When patients can’t tolerate methotrexate, it puts doctors in a conundrum, said Jeffrey Curtis, a professor of rheumatology and immunology at the University of Alabama at Birmingham School of Medicine. Methotrexate can lower the risk that patients start producing anti-drug antibodies, which are a particular problem when treating patient with monoclonal antibody drugs. Without methotrexate taken in combination with another drug, patients are less likely to respond well over time. ]

But there are promising monotherapy options for patients when methotrexate isn’t on the table. Rheumatology Network spoke with Dr. Curtis about the latest research and what’s in the pipeline.

What proportion of patients can’t tolerate methotrexate?

When a patient can’t or won’t take methotrexate, what are the next options?

If it’s that you can’t be on it at any dose, you have to be on monotherapy with something else. So then the question arises, ‘What should that something else be?’

What Are Standard Dosages For Methotrexate

Most people with RA begin with a 7.5 milligram dose of methotrexate tablets taken once a week. Over time, if that is not enough to help, your doctor will increase your dosage, perhaps to 20 milligram.

It is extremely important to understand that the drug is taken once weekly, not once each day, Tenpas says, noting that mistaking this dosage has led to toxicity in some patients.

Methotrexate can also be given by injection. People can give the methotrexate shot to themselves using an auto-injector. Taking the drug this way allows more of it to get into your system without increasing unwanted side effects.

Starting dosages for the injected drug are generally similar as for the oral version.

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Is There A Permanent Cure For Rheumatoid Arthritis

• Frequently Asked Questions

Rheumatoid arthritis is a chronic inflammatory disease that affects many joints, mainly the small joints of the hands and feet. It is a lifelong condition without a cure.

RA occurs when the immune system malfunctions and attacks healthy tissues. Untreated or severe RA can cause inflammation that also affects the organs. When RA attacks the joints, its target is the synovium . Over time, chronic inflammation can lead to bone erosion and joint deformity.

There is no permanent cure for RA. However, healthcare providers have many options for treating RA symptoms and getting the disease into remission. Remission is a time in which a person experiences few or no signs of the disease.

Keep reading to learn about how RA is treated, the latest research, and how remission in RA occurs.

How Long Does Methotrexate Work For

A clinical trial studied rheumatoid arthritis patients who took methotrexate for 12 weeks and then methotrexate was stopped. The methotrexate continued to be effective for 3 to 6 weeks after methotrexate was stopped and after this time the rheumatoid arthritis symptoms began to return.

Bottom line:

• Methotrexate starts to show improvements in rheumatoid arthritis symptoms in 3 to 6 weeks.
• Methotrexate is taken long term to reduce rheumatoid arthritis symptoms and reduce disease progression.
• If you stop taking methotrexate it will take 3 to 6 weeks for the methotrexate effects to diminish and your rheumatoid arthritis symptoms to reappear.

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In Combination With Other Drugs

Methotrexate is often used with other DMARDs or other medications for pain and inflammation. It has shown to be a great partner. Certain combinations of two or more DMARDsalways with methotrexate as one componentwork better than methotrexate alone. Keep this in mind if you dont respond to methotrexate by itself. You can talk to your doctor about a combination therapy.

Besides the fact that it works for many people, doctors like to use methotrexate because serious side effects are uncommon. But like all medications, methotrexate can cause side effects. Common side effects can include:

• upset stomach
• fatigue
• thinning hair

You may be able to lower your risk of these side effects if you take a folic acid supplement. Ask your doctor if this supplement is right for you.

In rare cases, methotrexate can cause serious side effects. These can include:

• cirrhosis
• low white blood cell levels
• low red blood cell levels
• low platelet levels
• lung disease

During treatment with methotrexate, your doctor may check your blood cell counts, liver function, and lung function. If you have serious side effects, your doctor may stop your treatment.

Data Collection And Analysis

Two review authors independently determined which studies were eligible for inclusion, extracted data and assessed risk of bias. Outcomes were pooled using mean differences for continuous variables or standardized mean differences when different scales were used to measure the same outcome. Pooled risk ratio was used for dichotomous variables. Fixedeffect models were used throughout, although randomeffects models were used for outcomes showing heterogeneity.

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Side Effects Of Methotrexate

Like all medicines, methotrexate can cause side effects, although not everyone gets them. Often side effects improve as your body gets used to the new medicine.

How Does Methotrexate Work Is It A Pain Pill

Methotrexate works on inflammation, it doesnt work on pain, Dr. Feldman explains. But your inflammation causes pain. Its not like someone poking you with a stick or having a headache. Methotrexate goes to the source of the problem, the inflammation. By reducing that inflammatory process, you help reduce the pain in a more directed way at the source and also in a more effective and long-lasting way. Methotrexate slows down the progression so it reduces the destruction of the joints.

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Lifestyle And Home Remedies

There are self-care steps you can take to manage RA. Along with your medications, the following can help with pain and other symptoms of RA:

• Exercise: Gentle exercise can help strengthen joints and muscles and reduce daily fatigue. You should check with your healthcare provider before starting any exercise routine and avoid exercising when joints are tender or inflamed. Walking, stretching, water exercises, swimming, and tai chi are all safe exercises for people with RA.
• Diet: There is no specific or recommended diet to treat RA, but some foods can help lower inflammation in your body. To manage RA, foods to add to your diet include fruits and vegetables, whole grains, fatty fish, and healthy oils like olive oil.
• Apply heat or cold: Heat can help to ease pain and relax stiff joints and muscles. Cold can help to dull down pain and decrease swelling.
• Relax: Find ways to reduce stress in your life to control RA pain. Try deep breathing, guided imagery, and other relaxation techniques.

What Is The Average Dosage For Injections

The average dosage for injectable methotrexate is the same as for oral methotrexate. The dosage is always weekly.

If a person does not respond well to oral methotrexate, they may respond better to the injectable form of the drug. This is because administering the drug under the skin allows it to bypass the digestive system. This helps methotrexate act more efficiently without increasing the risk of side effects.

• nausea
• vomiting

Many of methotrexates side effects happen because of the drugs effects on folate levels in the body. People may be able to alleviate the side effects by taking a daily folate or folic acid supplement. A doctor can provide instructions about the best dosage to try.

A healthcare professional may also recommend other measures to reduce side effects, such as splitting the dose, switching from oral methotrexate to injections, taking antinausea medication, and using a pain-relieving rinse for mouth sores.

A high or long-term dosage of methotrexate can be dangerous. In some cases, it can cause serious adverse reactions. For example, taking methotrexate for a long period can increase the risk of liver damage, particularly for those who:

• drink large amounts of alcohol
• have preexisting liver disease

People with a high risk of liver damage may not be able to take this drug. Other potential risks of methotrexate treatment include:

Methotrexate is also not safe for people who are pregnant or could be pregnant, or people who breastfeed.

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How Long Can You Take Methotrexate For

Methotrexate can be taken long term to help treat rheumatoid arthritis symptoms and also to help slow disease progression and joint damage. Rheumatoid arthritis is a chronic illness that does not have a cure, so medicines like methotrexate are taken to reduce the symptoms and reduce that damage caused by the disease.

There have been clinical trials that have lasted 11 years which have studied rheumatoid arthritis patients taking long term methotrexate.

These studies showed:

• sustained positive response with a 50% improvement in joint pain
• greater than 65% reduction in joint swelling index
• 11% of the patients left the study due to methotrexate toxic effects.

Is Methotrexate Safe If Im Pregnant Or Planning To Be

Methotrexate can cause birth defects. It can also increase the risk of infertility in men who take it. If you arent taking methotrexate yet and are planning to be pregnant, let your doctor know. They will likely recommend that you hold off on starting methotrexate. However, if you are already taking it, you may be asked to stop and wait 1 to 3 months before trying to conceive.

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Extra Care Is Needed When Taking Methotrexate

Make sure you take the right dose

Methotrexate tablets come in 2 strengths: 2.5 mg and 10 mg. When you collect your methotrexate prescription, check that your tablets are the right strength, and that you have the right number of tablets. If your tablets look different to your last supply, get advice from your doctor or pharmacist.

Blood tests

While you are taking methotrexate you will need to have regular blood tests. These check the treatment is working and monitor for side effects, measure kidney and liver function, and do a full blood count. Over time, these tests are needed less often.

Vaccines

It is safe for you to have the annual flu vaccine. Keep your flu vaccinations up to date to reduce your risk of getting the flu. Some vaccines should not be taken if you are taking methotrexate. Always check with your doctor or pharmacist first.

Sun protection

Methotrexate makes your skin more sensitive to the sun. Protect your skin when you are in the sun, especially between 10am and 3pm. If outdoors, wear protective clothing and use a high factor sunscreen .

Pregnant or planning a pregnancy

Methotrexate should not be taken if you are pregnant. If either you or your partner are taking methotrexate, talk to your doctor about contraception. If you or your partner wish to become pregnant, ask your doctor about stopping methotrexate. It should not be taken for at least 3 months before pregnancy.

Tell your healthcare providers

Proposed Mechanisms Of Action Of Methotrexate

Figure 1

Methotrexate-induced metabolic changes lead to increased extra-cellular adenosine. ADA = adenosine deaminase AICAR = aminoimidazolecarboxamidoribonucleotide AICAside = aminoimidazolecarboxamidoribonucleoside AK = adenosine kinase AMPDA = AMP deaminase DHF = dihydrofolate DHFglu = dihydrofolate polyglutamate ecto-5’NT = ecto-5’nucleotidase FAICAR = formyl-AICAR IMP = inosine monophosphate MTX = methotrexate MTXglu = methotrexate polyglutamate RFC1 = reduced folate carrier 1.

Another potential mechanism by which methotrexate may diminish inflammation in the joint is by diminishing cytokine production. Numerous studies have demonstrated diminished levels of inflammatory cytokines in the serum of patients. The adenosine A2A receptor agonist CGS-21680 is a potent inhibitor of neutrophil leukotriene synthesis in vitro, and, similarly, methotrexate therapy leads to diminished production of leukotriene B4 by neutrophils stimulated ex vivo. The mechanism by which methotrexate diminishes these cytokine levels remains unexplained and it is difficult to determine from these studies whether the effects of methotrexate therapy on production of inflammatory mediators results in diminished inflammation or is secondary to other anti-inflammatory events.

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What Is Humira Used For

People take Humira to treat rheumatoid arthritis that is moderate or severe. These patients are looking for pain relief, but the treatment should also prevent the progression of rheumatoid arthritis . Patients with RA are treated with medications, either alone or in combination, and when they are effective, they improve the possibility of obtaining symptomatic relief and slowing the progression of the disease. If you have RA, you know its not like standard arthritis, where you have stiffness and pain but no real progression of any disease process. While arthritis typically strikes older people, RA can occur in anyone, including younger people and even children.

Humoral And Cellular Immune Responses

Rheumatoid factor, or autoantibodies directed against the Fc portion of IgG, is a hallmark of RA, although its exact role in the pathogenesis of the disease has been debated. The effect of methotrexate on the levels of circulating IgM rheumatoid factors has also been controversial. While some workers have reported no suppression of serum rheumatoid factor levels with methotrexate treatment, Alarcon et al. observed significant drops in the levels of both IgM and IgA rheumatoid factors in methotrexate-treated patients, and particularly of the concentration of IgM rheumatoid factor in those who showed clinical improvement . These findings were confirmed by other groups in studies done both in vivo and ex vivo, although it is unclear whether this is a primary or secondary effect of adenosine.

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