Drug treatment of rheumatoid arthritis: an overview

Pain and inflammation control: non-steroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications in the treatment of rheumatoid arthritis. They are used in particular in the early phase of the disease or during acute flare-ups.

NSAIDs have an analgesic and anti-inflammatory effect. The most common NSAIDs include ibuprofen, acetylsalicylic acid (ASA), diclofenac and naproxen. They work by inhibiting the production of prostaglandins - substances that play an important role in the inflammatory response.

NSAIDs can relieve pain and inflammation in the short term and are used as painkillers for rheumatism. However, NSAIDs have no influence on the course of the disease or the underlying autoimmune reaction.

However, NSAIDs are not free from side effects. They can have an effect on the gastrointestinal tract (stomach ulcers, bleeding) and the cardiovascular system (increased risk of heart attack), particularly when used over a longer period of time. It is therefore recommended that NSAIDs are only taken in the lowest possible effective dose.

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Glucocorticoids: rapid inhibition of inflammation

Glucocorticoids such as prednisone or methylprednisolone are potent anti-inflammatory drugs that are often used to quickly control severe inflammation in RA. Glucocorticoids are also known colloquially as cortisone preparations. They work by suppressing the immune response and inhibiting pro-inflammatory cytokines, which play a central role in the disease process.

In practice, glucocorticoids are often used as bridging therapy. They are intended to bridge the time until a long-acting basic therapy (DMARDs) takes effect.

In the short term, they are very effective in suppressing inflammation and relieving pain. However, due to their side effects with long-term use, it is recommended to reduce the dose to a low dose range as quickly as possible in the individual situation and to phase out the medication in the long term.

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Basic therapy with disease-modifying antirheumatic drugs (DMARDs)

The basic therapy for RA aims to stop or at least significantly slow down the progression of the disease. Disease-modifying antirheumatic drugs (DMARDs) are used for this purpose. These modulate the activity of the immune system and thus attack the basis of the inflammatory process. The effect of almost all available drugs requires a certain amount of time and, depending on the substance and individual reaction, takes 4 to 16 weeks to be complete.

DMARDs are divided into two main categories: conventional synthetic DMARDs (csDMARDs) and biological DMARDs (bDMARDs).

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Conventional synthetic DMARDs (csDMARDs)

The csDMARDs include active substances such as methotrexate, sulphasalazine, hydroxychloroquine and leflunomide. These drugs are usually the first choice in the treatment of RA and are often used as monotherapy or in combination.

• Methotrexate is the most commonly prescribed DMARD and is considered the gold standard in RA therapy. It inhibits the activity of certain enzymes that are important for the inflammatory reaction and thus reduces disease activity. Methotrexate is taken in low doses once a week, but can cause side effects such as nausea, liver dysfunction and impaired haematopoiesis. Regular blood tests are therefore necessary.
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• Sulphasalazine is almost as effective as methotrexate, but causes slightly higher toxicity. Toxicity refers to a property of the active substance. A higher toxicity means that the active substance can be associated with more risks of side effects.
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• Hydroxychloroquine is often used as an alternative or complementary therapy, especially for milder courses. It has a lesser effect than methotrexate, but is also anti-inflammatory and well tolerated.
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• Leflunomide is another option that is used in particular for patients who cannot tolerate methotrexate or do not respond to it. Leflunomide has a similar effect to methotrexate, but can cause side effects such as diarrhoea and liver damage.

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Biological DMARDs (bDMARDs)

Biological DMARDs are biotechnologically produced drugs, so-called biologics. They intervene specifically in the inflammatory process by blocking specific molecules or cells of the immune system. They are generally used when csDMARDs are not effective enough or are not tolerated.

The bDMARDs include various classes of drugs that target different inflammatory factors:

• TNF inhibitors (e.g. adalimumab, infliximab, etanercept) block tumour necrosis factor-alpha (TNF-α), a key messenger of the inflammatory response. These drugs are particularly effective in controlling disease activity and can slow down joint destruction. However, they increase the risk of infections, especially tuberculosis.
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• IL-6 inhibitors (e.g. tocilizumab) inhibit interleukin-6, another cytokine that plays a key role in inflammation. These drugs are often used when TNF inhibitors do not work or are not tolerated.
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• B-cell therapies (e.g. rituximab) target the B lymphocytes, a cell group of the immune system that plays a role in antibody production and therefore also in the autoimmune reaction. This therapy is often used in severe cases or after other bDMARDs have failed.
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• T-cell costimulation inhibitors (e.g. abatacept) inhibit the activation of T lymphocytes, which are also involved in the inflammatory reaction.
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Biological DMARDs are usually administered as an infusion or injection and require regular monitoring in order to recognise side effects such as infections or allergic reactions at an early stage. They are also known colloquially as rheumatism injections.

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JAK inhibitors: A new generation of DMARDs

A relatively new class of active substances in RA treatment are the Janus kinase inhibitors (JAK inhibitors), such as upadacitinib, tofacitinib or baricitinib. These drugs work by blocking certain enzymes (Janus kinases) that are involved in the signalling of pro-inflammatory cytokines.

JAK inhibitors offer an effective alternative to biological DMARDs and can be taken orally. Here, too, there is an increased risk of infection, which is why regular checks are necessary.

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Single or combination therapy

The categories mentioned are not ‘either or’. Depending on the individual therapeutic situation, the drugs of the respective substance classes can also be combined with each other. The decisive factors here are the response, tolerability and risk of side effects.