Target-Specific DMARDs

Reviewed by: HU Medical Review Board | Last reviewed: May 2023

Disease-modifying anti-rheumatic drugs (DMARDs) have changed the way rheumatoid arthritis (RA) is treated. DMARDs not only treat the symptoms of RA, they have the ability to modify the disease course by slowing or preventing the damage to joints and surrounding tissues.

Target-specific DMARDs

There are different types of DMARDs: traditional (or conventional), biologic, and target-specific.

Target-specific DMARDs work by specifically targeting certain cellular enzymes to help reduce the inflammatory response that causes joint pain, swelling, and stiffness. While biologic DMARDs also target specific molecules, biologic DMARDs are made in the laboratory from living sources.

JAK inhibitors: a type of target-specific DMARD

The target-specific DMARDs currently available to treat RA are Janus kinase (JAK) inhibitors. JAK is a type of cytokine, or chemical messenger, that is believed to play a role in inflammation. In conditions like RA, the inflammatory response is overactive, and JAK inhibitors can reduce the inflammation and may stop joint damage that can be a long-term consequence of the disease. The three JAK inhibitors for RA are:

What is Xeljanz?

Xeljanz and the extended-release version Xeljanz XR are oral medications used to treat adults with moderately to severely active RA who have not had an adequate response or have experienced an intolerance to TNF inhibitors. Xeljanz may be used alone or in combination with conventional (non-biologic) DMARDs. Xeljanz should not be used in combination with biologic DMARDs or immunosuppressants like azathioprine or cyclosporine.1

Xeljanz may cause side effects, and some of them may be serious, including reducing a person’s ability to fight infections. Some infections can be life-threatening, and people should be tested for tuberculosis (TB) before starting treatment with Xeljanz. The most common side effects experienced with Xeljanz are upper respiratory infections, colds, headache, changes in cholesterol levels and diarrhea.1 These are not all the possible side effects of Xeljanz. Patients should talk to their doctor about what to expect with treatment with Xeljanz.

What is Olumiant?

Olumiant is a JAK inhibitor that is approved for the treatment of moderate-to-severe RA in people who have not had an adequate response to one or more anti-TNF (tumor necrosis factor) therapies. Olumiant should not be used in combination with other JAK inhibitors, biologic DMARDs, or with immunosuppressants like azathioprine or cyclosporine.2

In clinical trials, several potentially serious side effects were associated with the use of Olumiant, including serious infections, malignancies (lymphoma and other cancers), and blood clots (thrombosis). Serious infections may be viral, bacterial, or fungal, and may require hospitalization. Some infections may lead to death. Blood clots may also be fatal and include deep venous thrombosis (blood clot in a deep vein like the legs), pulmonary embolism (blood clot in the lungs), and arterial thrombosis (blood clot in an artery, which could cause a heart attack or stroke).2

The most common side effects experienced by patients in clinical trials receiving Olumiant were upper respiratory tract infections, nausea, herpes simplex and herpes zoster. Other side effects seen with Olumiant include gastrointestinal perforations and changes in blood work (white blood cell counts, red blood cell counts, blood lipids, and liver enzymes).2 These are not all the possible side effects of Olumiant. Patients should talk to their doctor about what to expect with treatment with Olumiant.

What is Rinvoq?

Rinvoq (generic name upadacitinib) is a drug that was approved for moderate to severe rheumatoid arthritis (RA) in August 2019. The drug is aimed at those who haven’t responded well to treatment with TNF inhibitors, or had no response at all to that drug.

Rinvoq can lower your immune system. People have developed serious infections while on the medication because of their lowered immune system, including tuberculosis (TB).3 This medication may also increase your risk of certain cancers because of the lowered immune system effects, including lymphoma and skin cancers, among others.3 Common side effects seen with this drug include nausea, cough, fever, and upper respiratory infections.3 These are not all the possible side effects of Rinvoq. Patients should talk to their doctor about what to expect with treatment with Rinvoq.

When are target-specific DMARDs used in RA?

Target-specific DMARDs are not used as first-line therapy (the first medication a person receives). Generally, these medications are used after a person has tried and not gotten an adequate response from other medications. In the case of Xeljanz, Olumiant, and Rinvoq, all are approved to be used after someone has previously tried one or more TNF inhibitors without success.1,2

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