How Does Methotrexate Work To Treat Rheumatoid Arthritis
Methotrexate belongs to a group of medications known as nonbiologic DMARDs . Examples of other nonbiologic DMARDs used to treat RA include , , and .;
We dont know exactly how methotrexate works to treat RA yet, but researchers agree that it has an effect on the immune system. Methotrexate is thought to prevent your body from mounting immune and inflammatory responses. One way researchers think it does this is by blocking the effects of folic acid, a chemical that supports the production of new cells. Methotrexate may also ramp up processes in your body that counteract inflammation.;
Doses For Inflammatory Conditions
For inflammatory conditions such as psoriasis, rheumatoid arthritis and Crohn’s disease, the dose will vary. This depends on your condition and blood test results. Always follow the instructions from your doctor.
For rheumatoid arthritis, the usual starting dose is 7.5mg, taken once a week. This can be slowly increased up to 20mg or 25mg once a week.
For psoriasis, the usual starting dose is 2.5mg to 10mg, taken once a week. It can be slowly increased up to 30mg once a week.
For Crohn’s disease, the usual dose to prevent flare-ups is 10mg to 25mg, taken once a week. This is often called a “maintenance” dose.
If your child is prescribed methotrexate, the doctor will use their height and weight to work out the right dose.
Folic Acid A Must For Ra Patients Taking Methotrexate
Though it may not seem like a supplement could do much to ease methotrexates potentially uncomfortable side effects, the Arthritis Foundation calls folic acid an absolute must. This is because it doesnt interfere with the drugs positive treatment effects, yet it does ease the angst that some people with RA develop in their gastrointestinal tract when taking this prescribed medication in its normal dose.
Additionally, one piece of research published in the journal Arthritis Research & Therapy explains that methotrexate toxicity can become an issue for patients with RA, especially if they take this drug over long periods. Essentially, one of the main problems occurs when it comes time for patients to be taken off methotrexate as withdrawal occurs as much as 50 percent of the time.
As a result, some doctors are hesitant to prescribe this drug as a treatment option to patients with RA. However, folic acid reduces this concern for these doctors in that it helps reduce methotrexate toxicity. Even in smaller doses, it has proven to be effective in this regard. There are other ways to reduce toxicity as well, such as by taking additional substances, like calcium folinate for instance.
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Optimal Methotrexate Dose For Rheumatoid Arthritis
The usual adult dose of methotrexate for rheumatoid arthritis is, as mentioned above, 7.5 milligrams as a single weekly dose. It can be taken as a divided dose: 2.5 milligrams taken orally every 12 hours for 3 divided doses over 36 hours once a week. The usual maximum weekly adult dose for oral methotrexate is 20 milligrams . The usual oral pediatric dose of methotrexate for rheumatoid arthritis is 5 to 15 milligrams once weekly.
According to research, the optimal evidence-based dose recommendation for adults with rheumatoid arthritis involves a starting dose of 15 milligrams of oral methotrexate once a week. That dose may be gradually increased to 25-30 milligrams per week or the highest tolerable dose. A switch to injectable methotrexate can be made by people with rheumatoid arthritis who achieve an insufficient response with oral methotrexate or for those who cannot tolerate the oral formulation. No matter what adjustments are made, it must remain as a weekly dose.
Can I Drink Alcohol While Taking Methotrexate
Methotrexate can affect liver function, which is why doctors will monitor your liver health closely while you take it. Methotrexate isnt recommended for people who already have chronic liver disease or who are heavy drinkers and have alcohol-related liver damage. Because there is potential for liver damage in people taking MTX, they shouldnt consume alcohol excessively.
For occasional drinkers, Dr. Feldman says the rules about how much alcohol is safe to drink while taking methotrexate depends on the rheumatologist. Some doctors insist on no alcohol at all, he explains. He tends to be a little looser with his patients. I tell my patients you can have a few drinks per week, just not all at once.
And dont have the alcohol two days before you get your blood drawn at the office, he adds, because the alcohol can mess up the liver function test and confuse your doctor. But he thinks a drink here and there is not dangerous for patients without any liver issues.
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How Well Does Methotrexate Work
The American College of Rheumatology recommends methotrexate as the first medication providers should consider when treating people with rheumatoid arthritis. In head-to-head clinical trials, methotrexate was found to be equally or more effective, and have fewer side effects, than other nonbiologic DMARDs. In most patients, it was also found to take effect faster.
Methotrexate can help improve symptoms and reduce the amount of joint damage that occurs because of RA. Some people who take methotrexate are even able to achieve remission, which is a long period of time without symptoms.;
You may be wondering if its worth it to take methotrexate when there are over-the-counter pain medications and steroid medications that can help ease inflammation. Unlike methotrexate, these other medications arent meant to be taken long term. They can rapidly control inflammation, but they dont really slow down how quickly RA gets worse. Taking them for too long can also lead to some serious risks. Theyre often recommended when patients start taking methotrexate and are waiting for the drug to take effect.
How Well Do The Drugs Work Are They Dangerous
All the drugs used to treat rheumatoid arthritis have been tested and have been proven useful in patients who have the disease. However, they all work on a different aspect of the inflammatory process seen in rheumatoid arthritis and their use as well as their side effects — depends on the current disease status of each patient and any associated medical problems that a patient may have. The effectiveness and the risks of drugs are considered when your rheumatologist plans your treatment.
If a drug is very effective in treating an illness but causes a lot of side effects, it is not an ideal treatment for long-term use. For example, high doses of corticosteroids can make people with rheumatoid arthritis feel dramatically better. However, high doses of corticosteroids may cause serious side effects when taken over many months or years. Steroids have many possible side effects, including weight gain, worsening diabetes, promotion of cataracts in the eyes, thinning of bones , and an increased risk of infection. Thus, when steroids are used, the goal is to use the lowest possible dose for the shortest period of time.
Testing for tuberculosis is necessary before starting anti-TNF therapy. People who have evidence of an earlierTB infection should be treated because there is an increased risk of developing active TB while receiving anti-TNF therapy.
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Methotrexate: Managing Side Effects
Folic acid supplements and monitoring tests are key for reducing your risk of methotrexate side effects.
Methotrexate is one of the most effective and widely used medications for treating inflammatory types of arthritis. Its also one of the safest arthritis drugs, despite a common misconception among many patients that methotrexate is highly toxic.;
Confusion about this medications safety seems to exist because it is also used; in much higher doses for treating some forms of cancer. Most;people;who use methotrexate to treat their inflammatory arthritis take between 10 and 25 mg;per week. By contrast, the doses used to treat leukemia and other types of cancer may be hundreds of times larger.;
Thats not to suggest that taking methotrexate is risk-free.;But doctors who prescribe methotrexate for arthritis say that following a few simple steps can make;it;even safer to use;and;reduce potential;side effects.;
Understanding how methotrexate works helps explain why it can cause unwanted effects.;Originally developed as a cancer drug, methotrexate;stops cancerous cells from rapidly multiplying and spreading by blocking their access to folate, a form of;vitamin B.;Unfortunately, depleting the body of folate can affect healthy cells, too, especially those in the gastrointestinal tract, mouth;and;hair follicles.;
Common Side Effects;
Side Effects Prevention Tips;;;
A few additional steps may help prevent or relieve GI and oral problems:;
Tumor Necrosis Factor Inhibitors
Tumor necrosis factor alpha is a pro-inflammatory cytokine produced by macrophages and lymphocytes. It is found in large quantities in the rheumatoid joint and is produced locally in the joint by synovial macrophages and lymphocytes infiltrating the joint synovium. TNF is one of the critical cytokines that mediate joint damage and destruction due to its activities on many cells in the joint as well as effects on other organs and body systems. TNF antagonists were the first of the biological DMARDS to be approved for the treatment of RA.; These drugs began to enter the market for rheumatoid arthritis in 1999 and are now considered a part the ACR recommendations for treatment of RA.;There are currently five TNF inhibitors FDA approved for the treatment of RA ; etanercept , infliximab , adalimumab , certolizumab pegol , and golimumab . Etanercept is a soluble TNF receptor-Fc immunoglobulin fusion construct; infliximab, adalimumab, and golimumab are monoclonal antibodies; and certolizumab pegol is an anti-TNF antigen binding domain-polyethylene glycol construct.; While differing in structure, the efficacy and safety of the drugs is similar across the class in reducing the signs and symptoms of RA, as well as in slowing or halting radiographic damage, when used either as monotherapy or in combination with methotrexate.
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How Long Will Methotrexate Take To Start Working
Its not immediate. Many RA patients will start to experience an improvement in symptoms after six to eight weeks on methotrexate, but it can take up to six months before you would reach the full benefits of taking the drug. If youre having a lot of debilitating RA symptoms, your doctor may prescribe corticosteroids as a short-term treatment to tamp down your RA flares while the methotrexate starts kicking in.
Its Normal To Have Questions About Taking Methotrexate Is It Really A Cancer Drug Can You Drink Alcohol Get Answers Here
Check any message board in a rheumatoid arthritis group on social media and theres one topic that pops up in posts constantly. It usually reads like this: My doctor prescribed me methotrexate and Im terrified. Should I take it? Then a stream of about 200 comments follows, about mouth sores and hair falling out and diarrhea, and it scares the beejesus out of you even more.
Taking any new medicine can be intimidating, especially one you might have to take for the rest of your life. Often, our doctors prescribe pills, injections, or infusions weve never heard of, and were either too shy or shocked to ask important questions about what the heck they are and what they might do to our bodies.
For anyone with RA, initiation into the MTX club seems particularly harrowing. I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasnt necessary to freak myself out. I wish I had known that but I, too, did not ask for or look for good information to ease my anxiety.
I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasnt necessary to freak myself out.
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Mtx Effects Via Adenosine Induced Immunosuppression
MTX typically blocks tetrahydrofolate dependent steps in cell metabolism. Because tetrahydrofolate and polyglutamyl derivatives of tetrahydrofolate are involved in purine biosynthesis several consequences can appear which result in adenosine overproduction. In purine biosynthesis two steps are tetrahydrofolate dependent . There is a preponderance of MTX mediated inhibition of the second enzyme AICAR formyltransferase in comparison with the first enzyme GAR formyltransferase .,
Adenosine increase by MTX and subsequent immunosuppression through adenosine receptors. MTX inhibits both, conversion of GAR â FGAR and AICAR â FAICAR. However, inhibition of the second step is stronger, which results in accumulation of AICAR. Accumulated AICAR inhibits AMP deaminase and adenosine deaminase , which increases adenosine-5â²-P and adenosine . Intracellular accumulation of adenosine-5â²-P and adenosine results in an increase of these compounds in the extracellular space. Here, adenosine-5â²-P is converted to adenosine, which binds to the specific receptor subtypes A1, A2a, and A2b . Probably, there will be a preponderance of the A2 receptor pathway, yielding an increase of cyclic adenosine monophosphate in the cell . cAMP increase leads to immunosuppression. AMP = adenosine-5â²-monophosphate; MTX = methotrexate.
Methotrexate Can Impact Vaccine Effectiveness
Because methotrexate affects the immune system, researchers have found that it can blunt the effectiveness of certain vaccines.
A small study published May 25, 2021, in the Annals of the Rheumatic Diseases, for instance, found that up to a third of people on methotrexate had a weaker immune response to the Pfizer-BioNTech COVID-19 vaccine. More than 90 percent of healthy people or those on TNF-inhibitors or other biologic drugs in the study produced adequate antibody levels with the vaccine, but only 62 percent of methotrexate users did.
It isnt clear exactly what this means for the vaccines effectiveness. But the American College of Rheumatology recommends delaying the dosing of methotrexate for a week after each shot for those with well-controlled disease.
Researchers have also documented diminished effects for the flu vaccine in people on MTX. In follow-ups, Korean researchers found that stopping the drug for four weeks, either the month after getting the flu shot or two weeks before and two after, increases immune response.
Anyone who takes methotrexate should work with their physician to discuss their specific drug regimen at the time of any vaccines.
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What Is Seronegative Inammatory Arthritis And How Effective Is Methotrexate In Treating It
Q) I’ve recently been diagnosed with seronegative inammatory arthritis and have been put on methotrexate. Could you please tell me what seronegative inammatory arthritis is, and what is the long-term prognosis? I’m 65 years of age and healthy, apart from this problem. How different is it from other forms of arthritis? How successful is methotrexate?
Vic Sibson, Broadstairs, Kent – 2008
A) Arthritis can be generally divided into seropositive and seronegative this refers to the presence in the blood of an antibody called rheumatoid factor. About 70 per cent of people with;rheumatoid arthritis are seropositive. So seronegative;rheumatoid arthritis occurs and this may be the diagnosis in your case. I say may be because there’s a group of disorders generally called seronegative spondyloarthropathy and these include ankylosing spondylitis,;psoriatic arthritis and reactive arthritis. My guess is that you havent got one of these conditions. Seronegative rheumatoid arthritis can be just the same as seropositive rheumatoid arthritis although on the whole it has a better outlook. If you dont feel the doctor has the time to explain things to you, try asking to see another member of the;rheumatology team a nurse,;physiotherapist or occupational therapist, or all three!
This answer was provided by Dr Philip Helliwell in 2008, and was correct at the time of publication.
How Can Methotrexate Be Disease Modifying
Methotrexate interferes with an enzyme important to DNA replication; this has the effect of inhibiting cell reproduction. Thats why its called an immunosuppressive drug. It is not known exactly how, but this suppresses immune activity.
Methotrexate is also referred to as a disease modifying anti-rheumatic drug or DMARD. It is called that because it can modify the course of an incurable disease. DMARDs can inhibit disease progression. This may mean remission for some patients and at least a great improvement of symptoms for most others.
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Nutritional Supplements And Dietary Changes
There’s no strong evidence to suggest that specific dietary changes can improve rheumatoid arthritis, although some people with rheumatoid arthritis feel their symptoms get worse after they have eaten certain foods.
If you think this may be the case for you, it may be useful to try avoiding problematic foods for a few weeks to see if your symptoms improve.
But it’s important to ensure your overall diet is still healthy and balanced. A Mediterranean-style diet, which is based on vegetables, fruits, legumes, nuts, beans, cereals, grains, fish and unsaturated fats such as olive oil, is recommended.
There’s also little evidence supporting the use of supplements in rheumatoid arthritis, although some can be useful in preventing side effects of medicines you may be taking.
For example,;calcium and;vitamin D supplements may help prevent osteoporosis if you’re taking steroids, and;folic acid supplements may help prevent some of the side effects of methotrexate.
There’s some evidence to suggest that taking fish oil supplements may help reduce joint pain and stiffness caused by rheumatoid arthritis.
- National Rheumatoid Arthritis Society : diet and rheumatoid arthritis
Page last reviewed: 28 August 2019 Next review due: 28 August 2022
How Can I Reduce The Nausea Caused By Methotrexate
Q) I’ve been taking;methotrexate for seven years,;but recently the feelings of nausea have increased and on the day I take it I feel quite sickly, with some diarrhoea at times. I’d like some advice on how this nausea could be lessened. I do take folic acid as prescribed. Is there any food to be avoided or guarded against on the day I take methotrexate? I dont want to interfere with this medication which has enabled me to live a near-normal pain-free life apart from some flare-ups.
Mrs M Slater, Lancashire – 2009
A) There are four ways of tackling this problem. Firstly, as you point out, folic acid taken on the non-methotrexate days can help. There’s a trend for people to take folic acid just once or twice a week so, if this applies to you, there’s an option of increasing the dose to six days a week. Secondly, your doctor or nurse can give you an additional pill to stop the nausea. This need only be taken on the same day as methotrexate. Thirdly, if you’re taking methotrexate tablets there’s an option to convert to methotrexate by injection quite a lot of my patients do this and find it more effective and less likely to cause sickness. Fourthly, if all else fails, the dose of methotrexate can be reduced, but this may require you to take additional treatment to keep your disease under control.
This answer was provided by Dr Philip Helliwell in 2009, and was correct at the time of publication.
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