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Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Medications to Treat Arthritis

Conventional DMARDs

What are conventional DMARDs?

Conventional disease-modifying anti-rheumatic drugs (DMARDs) are a class of medications used to treat inflammatory types of arthritis, such as rheumatoid and psoriatic arthritis. Persistent joint inflammation (swollen, tender, painful joints) can lead to joint damage if left untreated. Once a joint is damaged, the damage cannot be reversed. Early treatment aimed at reducing inflammation is important to prevent damage to the joint. This is where DMARDs can help. DMARDs work to suppress inflammation and help to prevent joint damage.

Using two or three DMARDs together is called combination therapy. Combination therapy with two or more DMARDs may be effective when single DMARD treatment is unsuccessful. Some studies suggest that starting therapy with a combination of DMARDs is better than starting with one medication. Your prescriber may recommend combination therapy to help treat your inflammatory arthritis. 

What are conventional DMARDs used for?

Conventional DMARDs are only used to treat inflammatory arthritis; they are not used in the management of osteoarthritis (OA).

How long do conventional DMARDs take to work?

DMARDs generally work well in most people; however, they may take six to 12 weeks to begin to have an effect. Shutting down the inflammatory process which causes inflammatory arthritis can take a long time, but the result of healthy joints will be worth the wait.

While you are waiting for your DMARD to take effect, your healthcare provider may prescribe an additional medication, such as prednisone or a non-steroidal anti-inflammatory drug (NSAID), to help control symptoms.

How are conventional DMARDs administered? 

Most DMARDs are taken orally in pill form. Methotrexate (MTX), a commonly used DMARD, can also be given by injection.

Which conventional DMARDs are right for you? 

Your prescriber will recommend a DMARD that is best suited to your type of arthritis, other medical problems and/or medications. Although DMARDs can be used one at a time, taking two or three together may be more beneficial, depending on your particular inflammatory arthritis. People with mild inflammatory arthritis may start with a single DMARD, such as hydroxychloroquine or methotrexate. However, those with more severe inflammatory arthritis may need more aggressive treatment and may receive two or three medications at the same time.

Conventional DMARDS and pregnancy

Please tell your healthcare provider if you are pregnant or planning to get pregnant before starting treatment with a DMARD. Certain DMARDs cannot be taken during pregnancy. Your healthcare providers can help devise a safe plan to treat your inflammatory arthritis while you try to get pregnant and during your pregnancy. 

How long will I have to take my conventional DMARDs?

Inflammatory arthritis is a chronic condition that will likely require life-long treatment. Treatment of inflammatory arthritis is usually a balancing act between taking as much medication as needed to control the arthritis and as little medication as necessary to minimize potential side effects. Your prescriber may adjust your medication dose, change or add medications to your treatment based on symptoms, findings on physical examinations and your laboratory tests. 

For more information about Conventional DMARDs, visit our Medication Reference Guide.

Biologic DMARDs

What are biologic DMARDs (biologics)?

Inflammation is one of the immune system’s first responses to help fight infection. It also aids the healing process when the body experiences trauma or injuries, such as a broken bone. Once the infection is cleared and/or bones are healed, the body “switches off” this response. For people with inflammatory arthritis, the immune system is overactive and their body does not appropriately “switch off” the inflammatory response. This inflammation then begins to attack normal body tissues and can cause damage in joint tissues. 

Biologic medications work by modifying the body’s inflammatory response. By decreasing the immune system’s attack on normal tissues, biologics, like disease-modifying anti-rheumatic drugs (DMARDs), can reduce pain, joint inflammation and damage to bones and cartilage. 

For some people living with inflammatory arthritis, a protein our body makes called tumor necrosis factor (TNF) is present in the blood and joints in excessive amounts, thereby increasing inflammation (pain and swelling). Adalimumab, certolizumab, etanercept, golimumab and infliximab are medications designed to block the action of TNF. Abatacept is a medication designed to interfere with the ability of the body’s immune T-cells (certain white blood cells) to communicate with each other. By blocking this interaction, the production of TNF is reduced. Other people with inflammatory arthritis may have an excessive amount of other inflammatory proteins called interleukins. Anakinra and tocilizumab are medications that block the action of certain interleukins. Rituximab is a medication designed to destroy the body’s immune B-cells, which play a part in the pain and swelling caused by inflammatory arthritis. By blocking TNF and interleukins, interfering with T-cell communication and destroying B-cells, biologics work to suppress the body’s immune system and decrease our inflammatory response. Although this suppression can make it slightly harder to fight infections, it also helps to stabilize an overactive immune system.

What are biologics used for?

Biologics are only used to treat inflammatory arthritis; they are not used in the management of osteoarthritis.

Biologics are typically used when inflammatory arthritis has not adequately responded to treatment with DMARDs. Biologics can be used alone to treat inflammatory arthritis but are often given in combination with DMARDs. The most common combination is with methotrexate (MTX). This is because combination therapy may work better than treatment with either medication alone. However, keep in mind that biologics are never used in combination with each other; it is not recommended because of the increased risk for infection.

How long do biologics take to work?

Biologics generally have a positive effect on the treatment of inflammatory arthritis; however, they can take time to work. Some people may notice the effects of the medication quickly (within days to weeks), while with others it may take three to six months to feel the full effects of the medication. It is important to be patient and keep taking your medication as prescribed.

How are biologics administered? 

Biologics are administered in two ways: infusion and injection.

An infusion means the medication is delivered intravenously (i.e., IV) via a needle in your arm. Each infusion will be carried out by a healthcare professional. The length of the infusion will range from 30 minutes to six hours, depending on the specific medication you are taking or the period of time your prescriber feels is best for you. The infusion can take place in a number of settings, such as your local hospital or specialty infusion clinics. All clinics are staffed by healthcare providers. Some medications may be administered in your home with the assistance of a healthcare provider. You will be monitored throughout the infusion and in some cases for a period of time after the infusion. The frequency in which you will require an infusion will depend on the specific type of medication you are taking.

A subcutaneous (s.c.) injection means that the medication will be delivered through a needle in the fatty layer of tissue under the skin of your abdomen or thigh (similar to how a diabetic would administer insulin). The medications are available in single-use, pre-filled syringes, containing the dose recommended by your prescriber. You can administer the injection yourself or a family member or friend can do this for you. Training and detailed instructions will be provided to you by your healthcare providers. If you prefer, you can make arrangements for a healthcare provider to administer the medication. 

Many of the biologic medications have special storage instructions which require them to be stored between two and eight degrees Celsius (in a refrigerator) in the original container until ready to use. Please ask your pharmacist how to properly store your biologic medication.

Which biologic is right for you? 

Your prescriber will recommend a biologic that is best suited to your type of arthritis, other medical problems and medications. Your prescriber will discuss the benefits of each biologic, how the medication is administered and its potential adverse effects. TNF blockers are currently the most commonly used first-line biologics, although other biologics may also be used. With many different biologics to choose from, if one doesn’t work, your rheumatologist may suggest another.

Biologic therapy is associated with a small increased risk of infections. Ideally, your vaccinations should be up to date prior to starting a biologic. If you have already started therapy with a biologic, most inactive vaccines are recommended, if indicated (e.g., influenza, pneumococcal). Live vaccines are not recommended due to risk of causing infection. Please speak with your healthcare providers about vaccinations before starting your biologic medication.

Your body may harbour the bacteria that can cause tuberculosis (TB) if you have been exposed to TB in the past. You may not know you are carrying TB as the bacteria remain in an inactive state and cause no symptoms. This is known as latent TB infection (LTBI). People with LTBI are not infectious and cannot spread TB to others. Biologics can increase the risk of reactivation of LTBI. Prior to starting biologic therapy, your prescriber will screen for LTBI. If you test positive you will be required to take an anti-TB medication prior to starting your biologic. Please talk to your healthcare provider about LTBI screening before starting a biologic.

Biologics have been associated with a small increased risk of developing certain types of cancer. Proof of a link between biologic medications and the development of cancer is difficult as people with inflammatory arthritis are generally at a higher risk of developing certain cancers, as compared to the general population. The role of biologic medications in the development of cancer is currently unknown. Please speak with your healthcare provider if you have any questions.

Biologics and pregnancy

Please tell your healthcare provider if you are pregnant or planning to get pregnant before starting treatment with a biologic medication. Biologic medications have not been studied in pregnant women or nursing mothers. Your healthcare providers can help devise a safe plan to treat your inflammatory arthritis while you try to get pregnant and during your pregnancy. Learn more here.

How long will I have to take my biologics?

Inflammatory arthritis is a chronic condition that will likely require life-long treatment. Treatment of inflammatory arthritis is usually a balancing act between taking as much medication as needed to control the arthritis and as little medication as necessary to minimize potential side effects. Your prescriber may adjust your medication dose, change or add medications to your treatment based on symptoms, findings on physical examinations and your laboratory tests.

What are biosimilars?

Biosimilars, or subsequent-entry biologics (SEBs) are similar to existing biologic medications. Biosimilars are made by a different manufacturer after the patent on the original biologic medication has expired. Biosimilars are sometimes mistakenly called “generic” versions of the original biologics. Unlike generics, which are identical copies of chemically made drugs, biosimilars are similar to, but not identical to the original biologic drug. This is due to the complexities of the manufacturing process of biologic medications. For more information on biosimilars, visit www.arthritis.ca/biologic.

For more information about Biologic DMARDs, visit our Medication Reference Guide.

Janus Kinase (JAK) Inhibitors

What are Janus Kinase (JAK) Inhibitors?

Janus Kinase or JAK inhibitors belong to a family of medicine called tsDMARDs (targeted synthetic disease-modifying anti-rheumatic drugs).  These drugs interfere with the activity of Janus Kinase enzymes in the body (JAK1, JAK2, JAK3, TYK2) in order to reduce the body’s overactive immune response.  In people with inflammatory arthritis, the body produces too many proteins called cytokines, which are involved in inflammation.  Some of these proteins bind to receptors on immune cells, and with the help of Janus Kinase enzymes, they send signals to the cells to turn on your immune system and create an inflammatory response.  JAK inhibitors interrupt the signaling process, reducing activation of your immune system cells and inflammation and damage to the joints.      

What are JAK inhibitors used for?

JAK inhibitors are only used to treat inflammatory types of arthritis; they are not used in the management of osteoarthritis (OA)JAK inhibitors are typically used when inflammatory arthritis has not adequately responded to treatment with conventional synthetic DMARDs. The most common combination is with methotrexate (MTX). This is because combination therapy may work better than treatment with either medication alone. However, keep in mind that JAK inhibitors are never used in combination with each other or with biological DMARDs; this is due to an increased risk for infection.

How long do JAK inhibitors take to work?

JAK inhibitors generally have a positive effect on the treatment of inflammatory arthritis; however, they can take time to work.  While some people may notice a benefit sooner, most people may start noticing the effects about two to eight weeks after they start taking the medication, while for others it may take three to six months to feel the full effects of the medication. It is important to be patient and keep taking your medication as prescribed.

How are JAK inhibitors administered?

JAK inhibitors are in the form of tablets and are taken orally.

Which JAK inhibitors are right for you? 

If you are prescribed a JAK inhibitor, your prescriber will recommend a JAK inhibitor that is best suited to your type of arthritis, keeping in mind other medical conditions and medications. Your prescriber will discuss the benefits of each JAK inhibitor, how the medication is administered and its potential adverse effects.

JAK inhibitor therapy is associated with an increased risk of infections. Ideally, your vaccinations should be up to date prior to starting a JAK inhibitor. If you have already started therapy with a JAK inhibitor, most inactive vaccines are recommended (e.g., influenza, pneumococcal). Live vaccines are not recommended due to risk of causing infections. Speak with your healthcare provider about vaccinations before starting your JAK inhibitor medication.

JAK inhibitors can sometimes cause anemia in patients, meaning that the body has a lower-than-normal number of red blood cells.  JAK inhibitors can also lower white blood cell counts and may increase cholesterol levels. Some patients may experience a greater chance of blood clotting while taking these medications as well. As they are still relatively new to the market, data regarding the long-term safety of JAK inhibitors is limited.

The most commonly reported adverse effects of JAK inhibitors in the first 3 months are upper respiratory infections, nausea, diarrhea and nasopharyngitis (i.e., symptoms similar to the common cold). Herpes Zoster (shingles) infections appear to be more common with JAK inhibitors than Tumor Necrosis Factor (TNF) inhibitor biologics. The risk of reactivation of latent tuberculosis infection (LTBI) associated with JAK inhibitors is similar to that of other biologic agents except for Rituximab, which generally carries a lower risk. Cases of non-TB opportunistic infections have also been reported with the use of some JAK inhibitors.  Other rare, but serious side effects specific to each JAK inhibitor are discussed in their respective monograph pages.

JAK inhibitors and pregnancy

Tell your healthcare provider if you are pregnant or planning to get pregnant before starting treatment with a JAK inhibitor medication. JAK inhibitors should not be used during pregnancy or while breastfeeding.  Currently there are no studies to assess the use of JAK inhibitors during pregnancy and breastfeeding.  Your healthcare providers can help devise a safe plan to treat your inflammatory arthritis while you try to get pregnant and during your pregnancy.

How long will I have to take my JAK inhibitors?

Inflammatory arthritis is a chronic condition that will likely require life-long treatment. Treatment of inflammatory arthritis is usually a balancing act between taking as much medication as needed to control the arthritis and as little medication as necessary to minimize potential side effects. Your prescriber may adjust your dose, change, or add medications to your treatment based on your symptoms, findings on physical examinations, and your laboratory tests.
 

For more information on Janus Kinase Inhibitors, visit our Medication Reference Guide.
 

This information was last updated January 2020, with expert advice from:

Hamidreza Izadpanah , Pharm.D.

Jason Kielly, B.Sc. (Pharm.), Pharm.D.
Associate Professor, School of Pharmacy, Memorial University of Newfoundland
Clinical Pharmacist, Rheumatic Health Program, Eastern Health