Features April 2013 Issue

New Drug Provides RA Relief in a Single Pill

Approval of oral biologic agent expands options for rheumatoid-arthritis patients.

A new medication offers patients with rheumatoid arthritis (RA) an alternative to the injectable drugs commonly used to manage the disease.

In November 2012, the U.S. Food and Drug Administration (FDA) approved tofacitinib, the first oral biological response modifier. The drug, marketed as Xeljanz, provides a new way to treat RA if other therapies prove unsuccessful.

“It’s an exciting advance,” says M. Elaine Husni, MD, vice chairman of the Department of Rheumatic and Immunologic Diseases and director of the Arthritis and Musculoskeletal Treatment Center at Cleveland Clinic. “I say it cautiously because the existing drugs we have are so good. Still, this is great that we have different mechanisms of action to treat rheumatoid arthritis because there are people out there who might not respond to the present treatments.”

A New Alternative
Oral nonsteroidal medications and non-biologic disease-modifying antirheumatic drugs (DMARDs) such as methotrexate are common first-line treatments for RA. Many patients, though, require more aggressive therapy with biological response modifiers, which slow inflammation by interfering with proteins called cytokines that regulate the intensity of your body’s immune response.

The biologic drugs adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi) and infliximab (Remicade) inhibit a potent cytokine known as tumor necrosis factor (TNF). Anakinra (Kineret) and tocilizumab (Actemra) target interleukin-1 and interleukin-6, respectively, two other key inflammatory cytokines. Other biologics—abatacept (Orencia) and rituximab (Rituxan)—block the activation of key immune cells. The biologic drugs are administered by injection or intravenous infusion.

Tofacitinib inhibits Janus kinase (JAK) enzymes, which signal the cytokines involved in RA joint inflammation. The FDA approved tofacitinib for use in patients with moderate-to-severe RA who do not respond adequately to methotrexate or cannot tolerate it. Clinical trials that led to the FDA approval demonstrated that tofacitinib was superior to placebo at reducing symptoms in these RA patients.

Some evidence also suggests the new drug may be beneficial when other biologic medications are ineffective. In a clinical trial involving 399 patients with moderate-to-severe RA and an inadequate response to the TNF inhibitors, investigators reported that use of a tofacitinib-methotrexate combination produced “rapid and clinically meaningful improvements” in RA symptoms and physical function compared to use of methotrexate alone. The study was published online in The Lancet (January 2013).

Despite these positive findings, Dr. Husni says she’s hesitant to prescribe tofacitinib ahead of other medications with longer track records.

“My first use of this drug will be for people who have failed more traditional treatments for RA,” she says. “I think tofacitinib will be ideal for someone not doing well on standard DMARDs or biologic DMARDs. But for a patient who’s never tried any of these more conventional DMARDs, it’s difficult to recommend a new drug that I have very little clinical experience with.”

Using Tofacitinib
Like other biologic DMARDs, tofacitinib may increase the risk of serious infections, tuberculosis and cancers such as lymphoma. Clinical trial data also suggest that the rate of shingles may be higher with tofacitinib compared to the other biologic drugs.

Before starting tofacitinib, you should undergo screening for tuberculosis and be immunized against influenza. Your doctor also may recommend vaccination against shingles and pneumonia.

Tofacitinib may cause low blood counts and increases in cholesterol and liver enzymes, so, as with other biologic drugs, you must undergo periodic monitoring with blood tests while on treatment.

A major selling point of tofacitinib is that it’s a pill, making it more attractive for RA patients who need biologic medications but aren’t fond of injections or infusions. However, the drug’s dosing schedule, 5 mg twice a day, may be problematic for people who have difficulty adhering to a medication regimen. Dosing of the other biologic drugs for RA ranges from weekly to as infrequently as every four to six months.

“It’s hard to say definitively that tofacitinib is much better because this is a medication that you have to take twice a day, every day,” Dr. Husni says. “I’m concerned about some compliance issues.”