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Target-Specific DMARDs

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. 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.

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 two 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 methotrexate. 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

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

When are target-specific DMARDs used in RA?

Target-specific DMARDs are not used as a 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, it is approved to be used after someone has previously tried methotrexate, and Olumiant is approved to be used after someone has previously tried one or more TNF inhibitors.1,2

  1. Xeljanz prescribing information. Pfizer, Inc. Available at Accessed 6/7/18.
  2. Olumiant. Eli Lilly and Company. Available at Accessed 6/7/18.