November 2013 -- An emerging class of medications called janus kinase inhibitors (JAK inhibitors, or jakinibs) is offering new hope to patients with rheumatoid arthritis (RA) who don’t find relief with other treatments.

Jakinibs were a hot topic at the American College of Rheumatology (ACR) 2013 annual meeting. Here’s what we know – and are still learning – about jakinibs and how they could help patients with rheumatoid arthritis.

What are Jakinibs?

Jakinibs are a new class of medication, sometimes called oral biologics. The word “biologic” is misleading, however, because jakinibs work in an entirely different way than the biologics that have been used to date. Jakinibs are small molecules that work inside cells. Traditional biologics such as etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia) and Infliximab (Remicade) block pro-inflammatory cytokines from outside

Jakinibs are taken by mouth. Traditional biologics are given through infusions or injections.

How do Jakinibs Work?

Jakinibs block the enzymes JAK1, JAK2, JAK3, and tyrosine kinase 2, which play a role in the cell-signaling process that leads to the inflammatory and immune responses seen in RA and other conditions. Jakinibs interrupt the signaling pathway.

“They are like the first translator. They are the molecules that take that signal from the cell surface and start moving it down the chain of command,” explains Donald Miller, Pharm.D, professor and chair of the pharmacy practice department at North Dakota State University in Fargo, N.D.

Are Jakinibs FDA Approved for RA?

Yes. The U.S. Food and Drug Administration (FDA) approved Xejlanz (tofacitinib) in November 2012 for adults with moderate to severe active RA who do not respond to or who cannot tolerate methotrexate. The 5-mg tablet is taken by mouth twice a day, alone or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). 

Tofacitinib was tested at two doses – 5 mg and 10 mg - but the FDA only approved the lower dose. Herbert Baraf, MD, a clinical professor of medicine at George Washington University School of Medicine in Washington, D.C., who participated in Phase III clinical trials of tofacitinib, says that’s a downside because the 10-mg dose had more significant positive x-ray data, in his opinion.

“Can you escalate the drug or cut the dose back if you need to and do you have another option to move on to? The answer with this drug is no because we have one only dose level,” says Dr. Baraf, who hasn’t yet prescribed the medication.

Are Jakinibs for My RA?

If your RA symptoms are well-controlled with methotrexate or biologics, a jakinib likely isn’t right for you. However, jakinibs could provide a great new treatment option if you have moderate to severe active RA and an inadequate response or intolerance to methotrexate.

Yet, it is unclear how these drugs specifically help improve symptoms. “My suspicion is that JAK inhibitors block multiple cytokines,” explains John O’Shea, MD, scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases who has worked with Pfizer on the development and research of jakinibs. “There are more than 200 cytokines and about 60 of them use the JAK pathway. In all the autoimmune diseases we have, we don’t know exactly which cytokine is the trouble maker.”