Medication to prevent joint damage

When disease-modifying treatment is started, doctors recommend using conventional DMARDs first. These include:

• Methotrexate (MTX)
• Leflunomide
• (Hydroxy)chloroquine
• Sulfasalazine

Methotrexate is considered to be the best tolerated of these drugs in the long term, so it is typically the first medication that is tried out. Methotrexate can be taken once a week as a tablet or injected as a solution. The dose is usually between 15 and 25 mg, depending on the person’s body weight, and it is gradually increased over the first few weeks of treatment.

The various conventional DMARDs work in different ways, and can have different effects in different people. So if one medication doesn’t help or isn't well tolerated, other medications can be tried out.

The choice of drug depends on various factors, including how doctors think the condition will develop, how far it has progressed, and whether certain medications can’t be used, for instance because the person has other medical conditions.

Generally speaking, rheumatoid arthritis treatment is started using methotrexate. Because it can take a while for methotrexate to start working, it is often combined with the steroid medication prednisolone at first. After a few weeks you have an appointment with the doctor to see whether the treatment is helping. The appointment involves physical examinations, blood tests and sometimes x-rays too.

After six months there should be a complete or at least very clear reduction in inflammation. If that hasn’t happened, methotrexate can be combined with a different conventional disease-modifying drug or with a biologic drug. If people have to stop using methotrexate because they don’t tolerate it well, they can carry on using only a biologic drug.

The aim of long-term treatment with disease-modifying drugs is to prevent joint damage, or delay it for a long time, if possible. Some people switch to a different medication after a while, for example because they don't tolerate the first medication well or because it’s no longer effective enough. Other people can reduce the dose and number of medications after a while. But disease-modifying drugs don’t have a noticeable effect in some people, so they stop using them.

Research has shown that conventional disease-modifying drugs can prevent damage to joints and relieve symptoms. These studies consider a treatment to be effective if it reduces swelling in the joints and at least three of the following improvements occur:

• The pain is relieved.
• The inflammation is reduced.
• Joint function improves.
• General health is rated better overall.

An analysis of methotrexate studies that lasted one year found the following:

• Symptoms were reduced by at least a half in 23 out of 100 people who took methotrexate.
• Symptoms were reduced by the same amount in 8 out of 100 people who took a placebo (fake drug) for comparison.

Symptoms like morning stiffness also improved in a lot more people who took a conventional disease-modifying drug.

There hasn’t yet been any good-quality research looking into whether one particular drug is more effective than any of the others.

Methotrexate is the most commonly used conventional DMARD because it is typically tolerated better than the others. But it still has various side effects. These include:

• Gastrointestinal (stomach and bowel) problems and nausea: in about 5 out of 100 people – particularly at the start of the treatment.
• Upper airway infections: About 12 out of 100 people had more colds or acute bronchitis infections within the first year.
• Hair loss: in about 5 out of 100 people.
• Inflammations of the membranes lining the inside of the mouth: in about 4 out of 100 people.

Most people can cope well with the side effects. But in about 3 out of 100 people the side effects are so bad that they stop the treatment.

Leflunomide, hydroxychloroquine and sulfasalazine can also cause side effects such as gastrointestinal problems and nausea. As well as that, leflunomide can lead to weight gain and an increase in blood pressure, sulfasalazine can cause allergic skin reactions, and hydroxychloroquine can lead to vision problems.

Many people accept mild side effects because the treatment is effective and helps them cope better with the disease in everyday life. And mild side effects are often only temporary. That was also shown in research: People who took these medications were more likely to continue treatment than those who used a placebo containing no active ingredient.

Some of methotrexate’s side effects occur because it interferes with the effect that folic acid has in the body. The risk of these side effects can be lowered by also taking low-dose folic acid (5 to 10 mg) once a week. Studies have shown that this helped more than half of the people who had side effects to continue their treatment with methotrexate.

It is also possible to inject the medication under the skin or into a muscle instead of taking a tablet: Side effects such as nausea, diarrhea and inflammations of the membranes lining the mouth are less common then.

Because of the increased risk of infections, the conventional disease-modifying drugs increase the risk of pneumonia. In very rare cases, the medications can cause other serious side effects too, such as liver damage or changes in blood cell count. In order to detect these kinds of serious side effects earlier, doctors regularly check blood and urine samples. It is generally always important to talk to a doctor if side effects occur.

When deciding which medication to use, it’s also important to take other medical conditions into account. For instance, in very rare cases hydroxychloroquine can damage the retina (lining of the back of the eye) so it isn’t suitable for people who have a retinal disease. Because sulfasalazine can lead to allergic skin reactions, it shouldn't be used in people who have certain allergies.

Methotrexate and leflunomide can lead to the development of birth defects in an unborn baby. There is some evidence to suggest that these drugs might damage the genetic material (genes) in men’s sperm too. So it’s important to use safe contraception if you are on these medications. It is still important to use safe contraception for some time afterwards as well: for six months after stopping treatment with methotrexate, and even for two years after treatment with leflunomide. Women who are breastfeeding also shouldn’t use methotrexate or leflunomide during that time.

Ideally, women who have rheumatoid arthritis and would like to have children should talk to their doctor before they get pregnant. Otherwise, they should do so as soon as they find out that they are pregnant.

There is also some evidence to suggest that methotrexate can reduce women’s and men’s fertility while they are taking them. Sulfasalazine can reduce men’s sperm count too.

Biologic drugs are made from living cell cultures. They work by, for instance, interfering with certain chemical messengers in the body’s immune system, and that influences the rheumatic inflammatory response. These drugs are also called biologic disease-modifying antirheumatic drugs (biologic DMARDs).

Biologics are considered as a treatment option for rheumatoid arthritis when conventional DMARDs haven’t helped enough. Biologics are typically used in combination with methotrexate. People who don’t tolerate methotrexate well can start treatment with a biologic only. All of the biologics approved in Germany so far are given as an injection or an infusion (a drip). It is also possible to inject the drug under your skin yourself.

The biologic DMARDs approved for use in Germany and other countries include:

• Abatacept
• Adalimumab
• Anakinra
• Certolizumab pegol
• Etanercept
• Golimumab
• Infliximab
• Rituximab
• Tocilizumab

Biologics can reduce pain, swelling and morning stiffness, and also help against fatigue. According to studies, people who use a biologic in addition to regular treatment with methotrexate more often have no symptoms or much fewer symptoms than people who are given only methotrexate.

But biologics can have various side effects too. For example, skin rashes, itching or pain can occur where the injection or infusion needle was inserted. They may lead to more frequent infections of the airways as well. 9 out of 100 people develop an infection of the airways, and 2 out of 100 have a severe infection.

Like biologics, the targeted synthetic drugs are an option if treatment with conventional disease-modifying drugs either doesn’t work or doesn’t have enough of an effect. They can then be used in addition or as an alternative. They are often combined with methotrexate, too.

These drugs are chemically synthesized active ingredients. They target specific substances in the blood (Janus kinases or phosphodiestaerase-4) that are involved in the development of rheumatoid diseases. Unlike the biologics, these drugs can be taken in tablet form.

The Janus kinase (JAK) inhibitors are:

• Tofacitinib
• Baricitinib
• Upadacitinib
• Filgotinib

Their effect is similar to that of the biologics. But because of their possible side effects, they aren’t an option for all people who have rheumatoid arthritis. Studies suggest that people with cardiovascular disease who take the JAK inhibitor tofacitinib, for instance, are more likely to develop thrombosis and embolisms.