Background treatments aim to slow the progression of rheumatoid arthritis. They act in a delayed manner and must therefore be associated with symptomatic treatments during the first weeks of the illness. Most of these medications also prevent or stabilize joint destruction. They are produced either by chemical synthesis or from a biological source (biomedicines).
Classical DMARDs for rheumatoid arthritis
Methotrexate is currently the first-line regimen prescribed in rheumatoid arthritis (except in particularly severe cases). Its mechanism of action is based on a reduction of the activity of the immune system and inflammatory reactions. A maximal response is usually achieved in the first six months, with improvement in symptoms, joint mobility and quality of life. It comes in tablet form (IMETH, NOVATREX, MEDROL), solution for injection in pre-filled syringes (IMETH, METOJECT), solution for injection in pre-filled pens (METOJECT, NORDIMET), solution for injection in ampoules (METHOTREXATE BIODIM). Whatever form it takes, methotrexate is taken once a week. Usually, methotrexate is given as an injection when the oral route does not give sufficient results.
Methotrexate is generally well tolerated: 50% of treated patients can continue treatment for at least three to five years. The most common side effects are digestive (diarrhea, nausea, etc.). Patients taking methotrexate are routinely monitored (clinical examination and blood test) for possible adverse effects, including hepatic, infectious, pulmonary and blood effects. In general, people taking methotrexate also take vitamin B9 (folic acid) to avoid certain side effects.
Sulfasalazine in rheumatoid arthritis
Sulfasalazine may be prescribed instead of or in addition to methotrexate. It is administered in progressively increasing doses. The side effects of sulfasalazine are mainly digestive: nausea and difficult digestion. Some patients do not tolerate it and develop hypersensitivity reactions.
Immunosuppressive drugs in rheumatoid arthritis
Immunosuppressive drugs are substances that decrease the activity of the immune system. They are indicated when methotrexate is not effective enough.
Leflunomide has similar efficacy and side effects as methotrexate. It can sometimes cause weight loss or decreased sensitivity of fingers and feet. It exposes a risk of malformations for the fetus in case of treatment of the mother or the father. This risk imposes effective contraception during the whole treatment and after the treatment (during a variable period to see with the doctor). The prescription of leflunomide is reserved for specialists in rheumatology or internal medicine.
Azathioprine can be proposed as a first-line treatment for rheumatoid arthritis, particularly in certain severe forms. This treatment exposes a risk of toxicity to the blood cells. Blood tests are prescribed at regular intervals to ensure that there is no abnormality.
Synthetic antimalarials in rheumatoid arthritis
Some antimalarials (chloroquine and hydrochloroquine) to prevent and treat malaria (malaria) also have anti-inflammatory properties that have long been used in the treatment of rheumatoid arthritis. They reduce the symptoms but do not prevent joint destruction. Today, their use is more limited, mainly in the treatment of early and less active forms of rheumatoid arthritis, in combination with methotrexate or sulfasalazine.
Chloroquine should not be used during pregnancy unless absolutely necessary or during breastfeeding. Men and women of childbearing potential must use effective contraception during treatment and for up to 8 months after discontinuation (see News: NIVAQUINE (chloroquine): contraindications during breastfeeding and effective contraception in adults in old age to procreate, 11/2018).
The most common side effects are digestive upset, rash, tinnitus and vertigo. There is a risk of an adverse effect on the retina (retinopathy) that requires regular eye examination.
Biological treatment of rheumatoid arthritis
Biologic drugs (biomedicines) used in the long-term treatment of rheumatoid arthritis act on the cells of immunity. As a result, they can reduce the body’s defenses against infections, and their use can lead to serious infections. Before starting treatment with these drugs, a preliminary assessment is carried out to detect a possible infection, including active or latent tuberculosis.
In addition to the risk of infection, these biological treatments may cause hepatitis B reactivation, cardiac involvement (heart failure for example), neurological disorders or severe allergic reaction (anaphylactic shock). Anti-drug antibodies can also develop.
Anti-TNF agents in rheumatoid arthritis
Anti-TNF agents (adalimumab, certozulimab, infliximab, golimumab, etanercept) block the action of a substance produced by the cells of immunity (the Tumor Necrosis Factor or TNF) which plays a central role in the progression of rheumatoid arthritis. The anti-TNF drugs have a faster and more effective action than methotrexate on the symptoms of rheumatoid arthritis and its progression. They are prescribed in combination with methotrexate or other basic therapy when rheumatoid arthritis is particularly severe, or when it continues to progress despite conventional DMARD.
Before the start of treatment, a dental checkup is carried out to detect an infection of the teeth that could be complicated by infection of the heart valves.
Anti-TNF agents are administered by injection, either intravenously at the hospital during the day or subcutaneously (by a nurse or the patient himself). Then, patients are regularly monitored to detect any infections as early as possible. When receiving an anti-TNF drug, it is important to remain alert and report to your doctor any signs that may suggest an infection: fever (even low) or weight loss (even moderate). Indeed, a neglected infection can have extremely serious consequences in people who receive anti-TNF.
Studies have shown an increased risk of certain cancers (lymphomas) when using anti-TNF agents in inflammatory bowel disease (IBD). Nevertheless, the risk of having a lymphoma remains low.
Abatacept in rheumatoid arthritis
Abatacept (ORENCIA) is a protein that has a targeted action on T cells. It is used, in combination with methotrexate, in the treatment of rheumatoid arthritis in case of insufficient response to a classical background treatment or from the outset in severe and progressive forms of the disease. This medication is given as weekly injections, either intravenously (in the hospital) or subcutaneously (by a nurse or the patient himself). Due to the risk of an allergic reaction, the first subcutaneous injection must be performed in a suitable care facility. Like anti-TNF agents, this substance poses a risk of infection and requires the same precautionary measures.
Rituximab in rheumatoid arthritis
Rituximab (MABTHERA, RIXATHON, TRUXIMA) is a monoclonal antibody that inhibits B-cells. Initially prescribed in the treatment of lymphoma, it has been shown to be effective in the treatment of certain autoimmune diseases, particularly in rheumatoid arthritis. It is reserved, in combination with methotrexate, for adults in whom the previously prescribed treatment regimens (including at least one anti-TNF) have failed to slow the progression of rheumatoid arthritis. It is presented as a solution for infusion and is administered in the hospital. Like anti-TNF, this substance exposes to a risk of infection, sometimes very serious, and require the same precautionary measures. Cases of serious skin reactions have been reported with rituximab. The occurrence of a rash requires discontinuation of treatment. Reactivations of hepatitis B virus have also been observed with rituximab. Screening for hepatitis B is recommended before starting treatment.
Interleukin-6 antagonists in rheumatoid arthritis
The interleukin 6 antagonists, tocilizumab and sarilumab, are monoclonal antibodies. They block the action of interleukin 6, a protein that plays an important role in inflammation and is present at high levels in patients with rheumatoid arthritis. They are used, in combination with methotrexate, in the treatment of moderate to severe active rheumatoid arthritis in adults, in case of intolerance or inadequate response to one or more treatments of funds (traditional or anti-TNF). They can be used alone in some cases. They are administered intravenously (only in the hospital) or subcutaneously.
Because of their mechanism of action, tocilizumab (ROACTEMRA) and sarilumab (KEVZARA) pose a risk of infections that may go undetected. The other main adverse effects are hyperlipidemia, digestive perforations, a drop in white blood cells and liver damage. The administration of these drugs should be monitored because of the risk of allergic reaction, rare but potentially serious.
Inhibitors of Janus kinases in rheumatoid arthritis
A new family of drugs is now available in the long-term treatment of rheumatoid arthritis. Unlike other biotherapies, which are all administered by injection, it is in the form of tablets to swallow. This family of drugs blocks enzymes, called Janus kinases (JAK), which play a role in the production of substances (cytokines) involved in inflammation and immunity. Two inhibitors of Janus kinases are marketed: baricitinib (OLUMIANT) and tofacitinib (XELJANZ). They are indicated in rheumatoid arthritis of adults, alone or in combination with methotrexate, in case of insufficient response or intolerance to other antirheumatic basic treatments.
The most common side effects are infections and hyperlipidemia (increased blood cholesterol), which is likely to lead to cardiovascular risk. Uncertainties exist on long-term tolerance.