Targeted Synthetic DMARDs

Disease-modifying antirheumatic drugs (DMARDs) have greatly improved treatment for rheumatoid arthritis (RA). People with RA now have more and better treatment options. DMARDs can change the course of the disease. They can slow or prevent damage to joints and related structures.^1,2

There are 3 types of DMARDs: conventional, biologic, and targeted synthetic. Targeted synthetic DMARDs block specific proteins to reduce inflammation. This can help reduce joint pain, swelling, and stiffness. Targeted synthetic DMARDs can increase your risk of infections and other side effects. Talk to your doctor about whether targeted synthetic DMARDs are right for you.^1,3

How do targeted synthetic DMARDs work?

Targeted synthetic DMARDs are small molecules made from chemicals in a lab. This is different from biologic DMARDs, which are made from living sources. Targeted synthetic DMARDs are designed to block specific proteins. This is different from conventional DMARDs, which act on the whole immune system.^1-3

Currently available targeted synthetic DMARDs work by blocking proteins called Janus Kinases (JAKs). JAKs are involved in the complex pathway that activates immune cells. Immune cells release a type of chemical called cytokines. The cytokines bind to proteins on other immune cells. This triggers JAKs to activate processes that lead to inflammation.^1,3

Drugs that block JAKs are called JAK inhibitors. They can reduce inflammation and stop joint damage in RA. JAK inhibitors have similar benefits and risks as biologic DMARDs.^1-3

Examples

Three targeted synthetic DMARDs are approved to treat RA. They are all JAK inhibitors. They are:^1-7

• Xeljanz® (tofacitinib)
• Olumiant® (baricitinib)
• Rinvoq® (upadacitinib)

These drugs differ in how much they block different JAK proteins. But we do not know how this difference affects clinical benefits. Some studies suggest that Olumiant or Rinvoq, combined with methotrexate, achieve the best results.^1,3

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Common side effects of targeted synthetic DMARDs include:^2,3

• Upper respiratory infections (common cold, sinus infections)
• Headache
• Diarrhea
• Nasopharyngitis (nasal congestion, sore throat, and runny nose)
• High blood pressure
• Acne

All currently approved targeted synthetic DMARDs have a boxed warning. This is the strictest warning from the US Food and Drug Administration (FDA). They have this warning because of rare instances of:^1,4-7

• Serious infections, especially tuberculosis and herpes
• Certain cancers, especially lung cancer and lymphoma
• Blood clots and heart problems

These are not all the possible side effects of targeted synthetic DMARDs. Talk to your doctor about what to expect when taking targeted synthetic DMARDs. You also should call your doctor if you have any changes that concern you when taking targeted synthetic DMARDs.

Other things to know

Take targeted synthetic DMARDs as your doctor prescribes. They are usually taken by mouth once or twice a day. Targeted synthetic DMARDs tend to start working within a few weeks.²

Your doctor will monitor you for side effects during treatment. They may perform certain tests before treatment. This includes screening for other health conditions, tests for tuberculosis, and other blood tests. Your doctor may also suggest appropriate vaccines before starting treatment.^2,3

Targeted synthetic DMARDs are not the first choice of treatment for RA. They are used when conventional and biologic DMARDs do not work. Your doctor may suggest combining targeted synthetic DMARDs with conventional DMARDs.^3,4

Before beginning treatment for RA, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs. Targeted synthetic DMARDs should not be taken with biologic DMARDs or immunosuppressants.³