DMARDs: disease-modifying anti-rheumatic drugs

Much of what eases sore joints only treats the symptoms. Painkillers dull the pain, anti-inflammatory tablets bring down the swelling and stiffness, and steroids settle inflammation fast. Each has its place, but they act on what the disease does, and once they wear off the process behind it carries on. Disease-modifying anti-rheumatic drugs, nearly always called DMARDs, are another matter. They work on the overactive immune response that drives inflammatory conditions such as rheumatoid arthritis, turning it down so that it does less damage, and in doing so they can slow, and often stop, the harm that unchecked inflammation does to the joints. That is the sense of disease-modifying: the illness itself takes a different course, rather than its symptoms going quiet for a few hours.

That difference decides how the medicines are taken. You reach for a painkiller when it hurts and leave it in the cupboard when it does not. A DMARD is taken regularly for the long term to keep the disease quiet, and its benefit grows over time instead of arriving with the first tablet, more like a blood pressure tablet than a headache remedy.

DMARDs are slow starters, and that is one of the hardest things about them. A clear difference usually takes several weeks, sometimes as long as three months, and the full effect may not come until around six months in. This does not mean the medicine is failing: these drugs bring an overactive immune system back into balance gradually; they do not switch it off.

Waiting in pain is hard, so a DMARD is seldom left to work alone at the start. A short steroid course, or a steroid injection, often bridges the gap until the slower medicine takes hold; our guide to steroids in rheumatology explains that part, and the warning signs to know while you take a steroid are in the lists under When to seek help. A steroid can also hide the usual signs of an infection, one more reason to ask your rheumatology team, your GP or NHS 111 about a fever or feeling unwell that same day, though the signs of sepsis under When to seek help are a 999 or A&E emergency. The waiting is worth it: what a DMARD offers is a lasting fall in disease activity, and with it, as inflammation stays down month after month, protection for the joints.

DMARDs are a family of medicines with one purpose and several ways of getting there, and they fall into three broad groups.

Conventional DMARDs (conventional synthetic DMARDs, to give them their full name) are the tablets with the longest record, and treatment usually starts with one of them. Methotrexate is used more than any other; sulfasalazine, hydroxychloroquine and leflunomide are among the alternatives, and two or more may be taken together. Their action is broad, on the immune response as a whole. Methotrexate is taken once a week, never daily, which is among the most important things to know about it, since taking it more often than prescribed can do serious harm; the methotrexate guide says what to do if a dose may have been taken wrongly.

Biologic DMARDs came later: medicines made from proteins produced by engineered cells, each aimed at a single messenger or cell of the immune system instead of the whole response. A protein would not survive being swallowed, so they go under the skin as an injection or, in some hospital settings, into a vein through a drip, usually after the conventional tablets have fallen short. They have a guide of their own, biologics and JAK inhibitors.

Targeted synthetic DMARDs, usually called JAK inhibitors, are the newest. These tablets switch off Janus kinases, enzymes involved in inflammation. Like the biologics, they aim more precisely than the conventional medicines, and they are usually considered once earlier treatments have fallen short.

Treatment with DMARDs now works to a plan called treat-to-target. Instead of starting a medicine and hoping, your team agrees a clear aim with you: remission, where little or no inflammation is left, or, if that cannot be reached, low disease activity. Each review then checks progress against that aim, and the treatment is stepped up, added to or switched for as long as the aim is out of reach.

That is why the reviews and the monitoring count for as much as the medicine. Whether inflammation is truly under control cannot be judged from how you feel alone, because a joint can stay quietly inflamed after the pain has gone. An examination, blood tests and, where they help, point-of-care ultrasound at the appointment show whether the inflammation has really settled, and that shapes the next step. All along, the goal is to keep the disease quiet on as little treatment as possible.

DMARDs share some safety themes, though not every theme applies to every one of them.

Regular blood tests belong to most of these medicines as much as the tablets do. Some DMARDs can occasionally affect the liver, the blood count or the kidneys, and such changes are usually picked up by the routine tests and dealt with early; hydroxychloroquine is the exception that needs no routine blood monitoring. The tests themselves are described in our guide to rheumatology blood tests. Turning up for each test is among the best ways to keep yourself safe.

Watching for infection matters because most DMARDs calm the immune system enough to make infections a little more likely and slower to clear. It is worth telling any healthcare professional that you take one, and asking your rheumatology team, your GP or NHS 111 for advice the same day if a fever appears or you feel unwell, though the signs of sepsis under When to seek help are a 999 or A&E emergency. Hydroxychloroquine is treated more lightly by the screening rules than the others: unlike them, it needs no screening for hepatitis or HIV before it starts. More detail is in our guide to infections and arthritis medicines.

Vaccinations need some forethought. Vaccines that are not live, among them the yearly flu vaccine and the pneumococcal vaccine, are recommended. The shingles vaccine now offered on the NHS can be given to people whose immune system is weakened, and you can check with your team whether you qualify. Whether a live vaccine is safe for you depends on your medicines and their doses taken together, so it is a decision for your team; who qualifies for which vaccine, and when, is covered in our guide to vaccinations.

A pregnancy needs talking about in good time. Some DMARDs, methotrexate and leflunomide among them, have to be stopped well before you try to conceive, while others, such as hydroxychloroquine and sulfasalazine, can often be continued, and the timing is different for each medicine. This is not something to work out alone or at the last minute; the reasons an early talk keeps the most choices open are in our guide to arthritis, autoimmune conditions and pregnancy.

Stop a DMARD only on advice. Stopping can be tempting when you feel better, or when the medicine does not seem to be doing much, but it can let the disease flare again. When side effects are the problem, talking them through is better than stopping without a word, since the dose can then be adjusted or another medicine chosen safely.

Day-to-day questions about a DMARD are for your next review. These two lists are for the signs that need more than that, the most serious first; they include the signs to watch for while a steroid is bridging the gap.

Treat any of these as a 999 or A&E emergency: call 999 and do not drive yourself to A&E.

• Severe illness with suspected sepsis: a high fever with shaking, confusion, rapid breathing, or feeling dramatically worse over hours
• With a fever or feeling unwell, a rash that does not fade when you press it, a stiff neck with eyes that cannot bear bright light, or skin, lips or tongue turning blue, grey, pale or blotchy, since these can be signs of meningitis or sepsis, as can a very bad headache, confusion or a first seizure with a fever or feeling unwell; on black or brown skin the rash and the change of colour may be easier to see on the palms of the hands or the soles of the feet
• Chest pain that is crushing, tight or like a pressure, that spreads to an arm, the jaw, the neck, the stomach or the back, that comes with breathlessness, sweating, feeling sick or feeling light-headed, or that came on suddenly and does not go away
• Breathlessness that is severe, with gasping, choking or no breath to get words out; or coughing up blood
• Palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, since a heart whose muscle or rhythm is affected has to be checked at once
• Any chest pain while you take sulfasalazine, which the NHS advice for this medicine treats as a 999 or A&E emergency
• A rash that spreads across the body, skin that blisters or peels, or lips, mouth or eyes that turn sore or swollen, since this can be a severe reaction to a medicine, such as Stevens-Johnson syndrome, which needs treating in hospital straight away
• Sudden weakness or numbness on one side, a drooping face or difficulty speaking, a sudden severe headache, sudden confusion or a seizure, or sudden loss of vision, any of which can be a stroke, even if it stops after a short time
• An eye that suddenly and completely loses its sight
• Vomiting that will not let your tablets stay down, or, during an illness or after an injury, becoming very drowsy or confused, or fainting, after more than a few weeks on steroid tablets, or repeated courses or injections in the past year, since your body may be running short of cortisol and the steroid may need to be given by injection; have your NHS Steroid Emergency Card ready
• Sudden severe pain in the abdomen or back, since the pancreas can react to prednisolone
• Lips, mouth, throat or tongue that suddenly swell, a throat that feels tight, very fast breathing or a struggle to breathe or to swallow, skin, tongue or lips turning blue, grey or pale (on black or brown skin this may be easier to see on the palms of the hands or the soles of the feet), becoming suddenly very confused, drowsy or dizzy, or fainting and not being able to be woken, since this can be a severe allergic reaction, anaphylaxis, which can follow a dose of any medicine
• Vomiting blood, or bleeding from the back passage that is heavy or will not stop, most of all with faintness, confusion or pain in the abdomen, or vomit that is black or dark brown, since a stomach ulcer on prednisolone can bleed
• Serious harm you have already done to yourself, such as an overdose, or a feeling that you may be about to harm yourself, since you need help to keep you safe now

Any of these needs an assessment that is urgent, on the same day, from your GP, your rheumatology team or NHS 111:

• A fever, or feeling generally unwell, on immunosuppressant, biologic or steroid treatment, since an infection has to be treated early; its first sign may be a cough, pain when passing urine, mouth sores or a wound that will not heal, though a wound with painful, hot and swollen skin around it belongs to the next line
• Skin that becomes painful, hot and swollen, around a cut or anywhere else, or redness that spreads, since this can be cellulitis, an infection of the skin, whose redness may be harder to see on black or brown skin; with a fever or feeling unwell, short of the signs that follow, at A&E or through NHS 111; with a very high temperature or feeling hot, cold or shivery, a fast heartbeat or fast breathing, purple patches on the skin, which may be less obvious on black or brown skin, feeling dizzy or faint, confusion, or skin that is cold, clammy or pale, it is a 999 or A&E emergency, as are the signs of sepsis in the first list
• A sore throat that will not go away, severe mouth ulcers, bruising or bleeding you cannot explain, skin that has turned paler than usual, or tiredness or weakness that is unusual for you, since these can point to an effect on the blood count, which a blood test can check
• A joint that is hot and swollen, with a fever or feeling unwell, since an infected joint has to be ruled out at once, at A&E or through NHS 111
• A joint that has become hot and very swollen suddenly, or is worsening quickly, even without a fever, since an infected joint does not always announce itself with one; a joint that will take no weight at all, or that cannot be moved, is a 999 or A&E emergency, whether or not there is a fever
• New chest pain, new palpitations, or breathlessness that is new or getting worse, since breathlessness can point to an effect on the blood count, and methotrexate can, rarely, inflame the lungs, so a new dry cough belongs here too, as the methotrexate guide explains; palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, belong to the first list, and so does any chest pain on sulfasalazine; in pregnancy, breathlessness that comes on suddenly, or when you lie down, or with dizziness, is for your midwife or maternity unit straight away
• Yellowing of the skin or of the whites of the eyes, or urine that has turned dark, since the liver can be affected by these medicines; on brown or black skin the yellow may be easier to see in the whites of the eyes
• Puffy hands, ankles or feet, or passing urine more or less often than usual, or in a larger or smaller amount, or not at all, since some of these medicines can affect the kidneys
• A new red, painful eye, or sight that has blurred, dimmed or changed, which needs an eye casualty or urgent eye clinic the same day, as does an eye that light hurts, since hydroxychloroquine, after years of use, can on rare occasions damage the retina at the back of the eye, and any red, painful eye is for an eye specialist to see; on hydroxychloroquine, a change in sight is also one to report to the team that prescribes it
• Thoughts of ending your life or of hurting yourself, or harm you have done to yourself that is not serious, short of the line in the first list, which steroids can bring on: ask your GP to see you that day or call NHS 111, and Samaritans answer at any hour on 116 123
• A marked change in mood or behaviour, confusion, or seeing or hearing things that are not there, on steroid treatment, since prednisolone can do this, the more so the higher the dose; confusion that comes on suddenly is a 999 or A&E emergency, as the first list says, and so, after more than a few weeks on steroid tablets, or repeated courses or injections in the past year, is becoming very drowsy or confused during an illness or after an injury
• Unusual thirst or hunger, passing urine more often, or feeling sleepy or confused, on steroids, or swelling of the arms or legs, bruising or bleeding that is not normal, black or dark red stools, severe stomach pain, severe back pain, a severe upset stomach, being sick, or very bad dizziness or passing out, since each can be a steroid effect that needs checking without delay; pain in the abdomen or back that comes on suddenly and severely is a 999 or A&E emergency, as the first list says, and so, after more than a few weeks on steroid tablets, or repeated courses or injections in the past year, is vomiting that will not let your tablets stay down, or, during an illness or after an injury, becoming very drowsy or confused, or fainting
• Contact with measles, chickenpox or shingles, since these infections can be severe on steroids and a medicine to protect you may be needed
• Being near someone with measles, chickenpox or shingles, while you take a medicine that weakens the immune system, since measles and chickenpox can be dangerous when the immune system is weakened, and you can catch chickenpox from someone with shingles if you have never had chickenpox; NHS 111 can tell you what to do that day

Other side effects, ones that are not in either list, are for your rheumatology team to hear about; a different dose or medicine can be tried, which is safer than stopping on your own. If you take methotrexate, the methotrexate guide's own lists hold further signs that belong to it, severe vomiting among them. If it is the arthritis itself that has flared, the managing flares guide is the one to read. If you take a biologic or a JAK inhibitor, the warning signs that belong to each are set out in our guide to biologics and JAK inhibitors. If you cannot tell how urgent something is, asking is never a mistake.

More is asked of you with a DMARD than with a painkiller: patience while it starts to work, regular blood tests, and staying on treatment even when you feel well. In return comes what no painkiller offers, a true change in the course of the disease and joints protected for the long term. Tests and reviews are no formality; they are what allows these medicines to be used both well and safely, finding problems early and keeping the disease quiet for years, not weeks. With a clear aim and close follow-up, these medicines have transformed life with inflammatory arthritis. At a specialist assessment, the medicine, the checks and a plan to fit your life are settled together.

What is meant by 'disease-modifying'?

That the medicine changes the course of the disease, not just how it feels. Pain relief and anti-inflammatory tablets help only while they act; once they wear off, the inflammation is still there. By damping the overactive immune response that drives the condition, a DMARD can slow or halt the joint damage inflammation would otherwise bring. That is why it is taken every week or every day for the long term, and not only during a flare.

How soon does a DMARD start to work?

More slowly than most people hope. A clear change usually takes several weeks, sometimes up to three months, and the full benefit may take around six months to arrive. Such a delay is expected and says nothing bad about the medicine. Because the wait is hard when you are sore, a short steroid course is often used to tide things over while the DMARD builds up; how that is done is set out in our guide to steroids in rheumatology.

Once I feel well, can I stop?

Usually not: feeling well is a sign the medicine is working, not that it is no longer needed. Stop a DMARD only on advice. Stopping can let the disease flare again. Side effects, or simply a wish to discuss it, are things to take to your rheumatology team, who can make any change safely.

Why are regular blood tests needed?

Some DMARDs can occasionally affect the liver, the blood count or the kidneys, and such changes are usually found by the routine tests before they cause any trouble. The tests are an ordinary part of the treatment, not a sign that something has gone wrong; hydroxychloroquine is the exception that needs no routine blood tests. What each test looks for is set out in our guide to rheumatology blood tests.

Will I catch more infections?

Most people on a DMARD do not find they catch infections often, but because most of these medicines calm the immune system, an infection can be a little more likely and slower to clear. Being watchful rather than worried is the right balance: tell anyone who treats you that you take a DMARD, keep your recommended vaccinations up to date, the yearly flu vaccine among them, and ask your rheumatology team, your GP or NHS 111 for advice the same day if a fever appears or you feel unwell, though the signs of sepsis under When to seek help are a 999 or A&E emergency. More on this is in our guide to infections and arthritis medicines.