Patience White, MD, vice president for public health at the Arthritis Foundation and professor of medicine and pediatrics at George Washington University School of Medicine in Washington, D.C., says she believes the panel’s recommendation is the start of a positive development for RA patients. “As a rheumatologist, I think it’s an exciting decision, because it gives a new option for patients who have not responded to the current therapies,” she says. “I am thrilled about the decision but also know I have to be judicious in who I would recommend this drug for because, like all drugs, it has a side effect profile we don’t know enough about.”

The advisory committee reviewed data from five phase 3 studies from Pfizer involving nearly 5,000 patients who hadn’t responded well to other RA drugs on the market, such as methotrexate or TNF-alpha blockers. The studies showed more patients experienced a 20 percent reduction in markers of disease activity when taking 5 mgs of the medication compared with those taking a placebo. Percentages of improvements were even higher among those on the 10 mg dose. Four studies showed patients taking the new medicine had improvements in their physical function, too.

In addition to reviewing scientific data, the panel members also heard comments and testimony from the public, including that of Jan Wyatt, RN, PhD, a member of the Arthritis Foundation's board of directors and an RA patient.

“I think it has a lot of exciting potential. If it would be as effective as the biologics and have the convenience of oral administration, it would obviously be a very attractive medication,” says Donald Miller, professor and chair of the pharmacy practice department at North Dakota State University in Fargo.

In its briefing documents, the FDA staff members did raise concerns about whether the benefits of tofacitinib outweigh the risks, which include increased rates of malignancies, particularly lymphoma. Study participants also experienced an increased risk of infections like pneumonia, saw their cholesterol levels and their liver enzymes rise and had increased rates of neutropenia, a condition in which the body’s white blood cell count gets low, making it hard to fight infection.

Because tofacitinib is part of a new class of drugs, its potential risks and benefits are different than those of traditional DMARDs, like methotrexate, and biologics. This point was highlighted by Sarah Yim, MD, associate director of the Division of Pulmonary, Allergy, and Rheumatology Products at the FDA. In those briefing documents, she wrote, “As a new molecular entity targeting a novel pathway in RA, tofacitinib may have a unique benefit-risk balance that cannot be inferred from previous experience with other products approved for RA.”

Pfizer says long-term studies are currently underway to better understand the pill’s long-term effects, but stresses that current research is promising and shows the drug is ready for the market. “We have seen benefits as early as two weeks and the efficacy was maintained up to three years in long term studies,” explains Tamas Koncz, MD, PhD, Pfizer’s Global Medical Leader for tofacitinib. “The efficacy profile and the safety profile is in line with the currently available treatment options.”

But, Miller says, it’s hard at this point in the process with any new medication to fully understand how a wide variety of patients will react to it in real-world conditions. “It’s been a couple thousand patients studied [so far], and when it comes on the market, it will be used by tens of thousands. That’s when a more rare side effect would be seen,” he says. “We need a few years of experience in wide use to see how its safety matches up to the biologics.”

For that reason, many rheumatologists say that for the vast majority of their patients, they’ll continue to rely on RA medications that have been available for years, even if tofacitinib becomes available. “It’s not a first-line drug for several reasons,” explains Daniel Furst, MD, director of rheumatology and therapeutic research at the Geffen School of Medicine at the University of California, Los Angeles. “We don’t have the long-term experience with it. We don’t know the long-term cardiovascular outcome, and we do have that experience with other drugs. I think it is very effective and I think it will be a significant advance, but you never get something for nothing, and there is definite baggage that goes along.”

Scott Zashin, MD, a clinical professor of medicine at the University of Texas, Southwestern Medical School and an attending physician at Presbyterian Hospital in Dallas, agrees that tofacitinib, while promising, likely won’t be something that he rushes to offer most of his patients.

“I tend to steer my patients to drugs that have been around for years and have a long-term track record,” Dr. Zashin explains, but notes that tofacitinib may be a good option for RA patients who don’t respond well to current treatments.