Disease-modifying antirheumatic drugs (DMARDs)
“Disease-modifying antirheumatic drugs (DMARDs) are essential for managing RA and they’re designed to reduce or prevent joint damage and to preserve your joint function,” says Dr Ann.
- there are 3 main types – traditional DMARDs, biologic DMARDs and JAK inhibitors (targeted synthetic DMARDs)
- stick with them – they can take several months to start working effectively
- your doctor may prescribe other drugs alongside them – such as non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, to tackle swelling and pain while you wait for the DMARDs to work
Traditional DMARDs
“Also known as non-biologic DMARDs, these are very effective and can help prevent the pain and stiffness caused by joint damage,” says Dr Ann. “They calm down your body’s overactive immune system to stop it damaging your joints.”
- your doctor will usually start you on a lower dose and gradually increase it
- gradually increasing your dose helps manage the potential side effects – not everyone gets side effects, and for many people the benefits outweigh the risks, but you’ll decide this with your doctor
- you’ll need regular blood tests – to check your liver health and for toxicity, so you’ll need to fit these into your life
- they may become less effective over time – and you may have to move on to another type of drug
“Generally, they’re worth sticking with because they do control the disease,” says Dr Ann. “If you get symptoms you think might be side effects, keep a note of them and talk to your doctor to work out the best plan for you.”
Methotrexate
- this is an ‘immunosuppressant’ that slows down your body’s immune system and works to reduce inflammation
- it can reduce pain, stiffness, and long-term joint damage
- common side effects include a sore mouth and stomach upsets. These may affect up to 1 in 10 people, meaning 9 out of 10 people won’t get them
- you take it weekly (on the same day) as a pill, liquid, or prefilled methotrexate injection pens or syringes
- once your dose has been adjusted to full strength, it can take 3 months to feel the effects
- you can’t take it if you’re pregnant, and need to stop taking it 6 months before you try for a baby (as does your partner if he’s taking it)
- whether you can breastfeed while taking it depends on your dose, how you take it and if you’re taking other medicines
- you need regular blood tests for liver and kidney function. Initial tests are done every 1 to 2 weeks, and every 2 to 3 months when the dose is stabilized
- you may also need to take a folic acid supplement to help reduce side effects such as nausea, vomiting and diarrhea. This helps by protecting healthy cells
Sulfasalazine
- sulfasalazine works to reduce inflammation
- it can reduce redness and swelling, and is believed to aid healing
- potential side effects include nausea, vomiting, diarrhea, stomach pain and indigestion, which affect more than 1 in 100 people
- you take it daily as a pill, liquid or a medicine you insert into your bottom (suppository)
- it can take 1 to 3 months before your symptoms get better
- you can’t take it if you’ve had previous allergic reaction to sulfasalazine, aspirin or similar drugs
- you need regular blood tests to monitor your blood count
Hydroxychloroquine
- originally developed for treating malaria, it can be used in the early stages of RA because it’s thought to interfere with the way cells in your immune system communicate with each other
- it can reduce joint pain and swelling. It may also help prevent joint damage and long-term disability
- the most common side effects are nausea, stomach pain, loss of appetite, headache and skin rashes (these affect more than 1 in 100 people)
- it’s taken daily as 1 dose or 2 divided doses
- it can take 2 to 3 months to see the effects
- you can’t take it if you’ve had a previous allergic reaction, are pregnant, breastfeeding or trying to become pregnant, have eye problems related to the retina or have psoriasis
- your doctor will monitor you closely with regular blood test to check the number and type of cells in your blood, and also check on your muscle and tendon function
Leflunomide
- works by stopping your body’s production of inflammatory cells
- it can reduce the inflammation which causes pain, stiffness and swelling in your joints
- side effects can include skin rash, temporary hair loss, abnormal liver function, nausea, diarrhea, weight loss, abdominal pain and raised blood pressure – these may affect up to 1 in 10 people
- it’s taken daily as a pill
- it takes 4 to 6 weeks before you feel any effects, but may take 4 to 6 months before you get the full benefits
- you can’t take it if you’re pregnant, breastfeeding or trying to become pregnant, if you’ve had liver problems, are taking other medications or herbal remedies, have a weak immune system, kidney problems, nerve problems or history of tuberculosis (TB)
- you’ll need regular blood tests to check for liver damage and other toxicities
- it can be used on its own or with other DMARDs such as methotrexate injections
Azathioprine
- this is an immunosuppressant so it works by calming your immune system
- benefits include reducing inflammation which causes swelling and pain in your joints
- nausea and headaches are common side effects that affect more than 1 in 10 people
- it’s taken once or twice a day as a pill
- it can take up to 12 weeks to feel the benefits after you’ve found your ‘right’ dose
- you’ll need to have regular blood tests while taking it
- you can’t take it if you’re pregnant or trying to become pregnant, if you’ve had a previous allergic reaction to it, have an infection/high temperature or feel generally unwell, if you’ve ever had liver problems or have had cancer
- it’s used much less than it was in the past because more effective treatments are now available. Whether you’ll be prescribed it depends on which drugs are available, your health and if you get any side effects
- it’s usually used as an add-on treatment to a main DMARD to help reduce steroids being taken if you have severe active RA
Biologic drugs
Biologic DMARDs are also known as biologic agents, targeted biologic agents and targeted synthetic DMARDs.
They work by blocking the activity of specific chemicals, cells and proteins involved in inflammation, which cause joint swelling and other RA symptoms.
“Biologic drugs are usually the next stage of the treatment ladder, as they target specific aspects of the body’s immune response, rather than many,” explains Dr Ann.
“They still have side effects – they suppress your immune system and so increase your risk of infections.
“There are several different types of biologics and they tend to work much quicker than conventional DMARDs – some within 2 weeks, others within 4 to 6 weeks.”
Anti-TNF drugs
- they work by targeting a protein called tumor necrosis factor (TNF) which is involved in inflammation
- drugs in this group include adalimumab, certolizumab, etanercept, golimumab, infliximab
- they have an anti-inflammatory effect, reducing pain, swelling and stiffness in your joints
- common side effects that affect more than 1 in 10 people include headaches, injection site reactions, rash, anemia, cough, diarrhea, nausea and abdominal pain
- most of these drugs are given by shot or infusion – how often you have this depends on the specific drug you need
- they take between 2 and 12 weeks to take effect
- your doctor won’t prescribe adalimumab – 1 of the most widely used anti-TNFs – if your RA isn’t active, if you have an infection, or there are other treatments you could try first. It’s also not suitable if you have certain health conditions
- if you’re pregnant, planning to get pregnant or you want to breastfeed, discuss your medication with your doctor. Whether you should take these drugs during pregnancy or breastfeeding can vary
- you’ll need blood tests while you’re on anti-TNFs to monitor their effects
Rituximab
- this is a monoclonal antibody, a type of protein that can bind to B cells (a type of white blood cell) in your body. B cells make antibodies but they can also produce harmful autoantibodies which can attack the tissue surrounding your joints in RA
- rituximab attaches to a molecule on B cells which triggers your immune system to destroy the B cells, reducing the number of autoantibodies
- benefits include reduced pain, improved function and fewer flare-ups (this is when your symptoms get worse temporarily)
- it’s used to treat RA that hasn’t improved with other types of medication
- the most common side effects are infusion-related reactions (such as fever, chills, and shivering). Fewer than 1 in 100 have severe reactions
- it’s given as an IV infusion, initially 2 weeks apart. The infusions are repeated when your symptoms begin to return. This could be between 6 months to a few years later
- it can take 8-16 weeks to notice an improvement after starting treatment
- it’s generally recommended not to take rituximab if you’re pregnant, as it can cross your placenta and may affect your baby
- you shouldn’t breastfeed during rituximab treatment and for 12 months after
- If you’re pregnant or thinking about becoming pregnant or you’re planning to breastfeed, speak to your doctor
- you’ll need monitoring with monthly blood tests
Tocilizumab
- another type of monoclonal antibody and it targets a protein called IL-6 which can cause inflammation if you have too much of it
- tocilizumab blocks the action of IL-6 in your body reducing inflammation and damage
- common side effects include abdominal pain, anxiety, cough, diarrhea, dizziness, increased risk of infection, insomnia or nausea
- it can be given as an intravenous infusion every 4 weeks, or as a weekly shot
- it generally takes 3 to 6 months to feel the benefits, but some people feel them sooner – as early as 2 weeks
- you can’t take it if your RA isn’t active, if you have a severe infection or you haven’t tried other treatments first
- you should generally avoid it during pregnancy, as its effects on the baby are not yet known. Speak to your doctor if you’re pregnant or planning to get pregnant
- talk to your doctor if you’re thinking of breastfeeding as the research is limited
- you’ll need blood tests every 4 to 8 weeks while you’re taking it
Biosimilars
There’s also a new generation of biologic-related drugs called biosimilars. These are very similar to biologics, they have the same benefits and potential side effects, but they’re cheaper to produce.
JAK inhibitor drugs
Janus kinase (JAK) inhibitors are the newest class of drugs used to treat RA. Also known as kinase inhibitors or targeted synthetic DMARDs, they include tofacitinib, baricitinib, filgotinib and upadacitinib.
Here’s what you need to know:
- like biologic drugs, they’re ‘targeted’ medication – but they’re easier to take, as they can be taken as pills
- they work by reducing your immune system’s ability to make certain proteins that play a role in inflammation
- they can reduce pain and swelling in your joints, and improve your daily function
- common side effects that may affect up to 1 in 10 people – meaning at least 9 in 10 people won’t get them – include nose, throat and windpipe infections, lung infections, shingles, flu, cystitis, dizziness and nausea
- depending on which medication you take, you’ll usually take pills daily or twice daily
- they can work in as little as 2 weeks in some cases, but in most people it takes 3 to 6 months to feel the benefits
- these drugs should only be used if there are no alternatives if you’re over 65 years old, if you’re at increased risk of heart attack or stroke or you smoke. That’s because of the increased risk of serious side effects including heart attack, stroke, cancer, blood clots and death. Caution is also needed if you have risk factors for blood clots or cancer
- they aren’t suitable if you’re pregnant, planning to become pregnant or you’re breastfeeding. Talk to your doctor if this is you
- you need regular blood tests while on JAK inhibitors, including a full blood count, liver enzymes and kidney function