A new drug that has been in the pipeline and could revolutionize rheumatoid arthritis (RA) treatment has been recommended for FDA approval by an independent arthritis advisory committee this past May. 

The U.S. Food and Drug Administration (FDA) is not expected to make a final decision until August, but if approved, tofacitinib, manufactured by Pfizer, will be the first oral disease-modifying antirheumatic drug, or DMARD, approved by the FDA in more than a decade.

"It is very effective," says Herbert Baraf, MD, clinical professor of medicine at the George Washington University School of Medicine, who participated in phase III clinical trials of the drug. "Eventually it may be a stand-alone therapy, but its place in the scheme of things is similar to most biologics. It's a non-injection option when it's time to move to something stronger."

In the past, the drug has been referred to as an oral biologic, but the DMARD is actually part of a new class of drugs called JAK inhibitors.

The likelihood that the FDA will approve tofacitinib is high. The independent advisory committee recommended that the FDA approve the drug by a vote of 8 to 2 for patients with moderate to severe RA and who have not responded to at least one other currently available treatment. The recommended dosages are 5 mg or 10 mg twice a day.

Five phase III studies involving nearly 5,000 patients who had not responded well to other RA treatments showed more patients experienced a 20 percent reduction in markers of disease activity when taking 5 mg of the medication compared with those taking a placebo. Percentages of improvement were even higher among those taking a 10 mg dose.

During the 2010 Annual Meeting of the American College of Rheumatology (ACR), it was reported that 66 percent of trial participants achieved a 20 percent or greater reduction in the number of tender and swollen joints while taking tofacitinib, and the drug also was shown to slow structural joint damage.

Not Another Biologic

Tofacitinib's effectiveness is being compared to that of biologic drugs, but the two work very differently. Biologic response modifiers are made from living organisms and fight inflammation by blocking cytokines such as tumor necrosis factor (TNF) and intlerleukin-6.

Tofacitinib, however, is in a new class of drugs called JAK inhibitors, so-named because they block Janus-associated kinase, or JAK, pathways that are involved in the body’s immune response.

So essentially, while biologics block pro-inflammatory cytokines from outside the cell, tofacitinib fights inflammation from inside the cell – a bit farther along in the process. 

“Whereas you block the TNF from binding to its receptor the way our [current] biologics work, these therapies block the transduction of that signal that occurs after that TNF protein binds to its receptor,” says Stanley B. Cohen, MD, clinical professor in internal medicine at the University of Texas Southwestern Medical School. “So the end result is you’re blocking the ability of that cell to become angry and make more inflammatory proteins.”

For patients with RA and the physicians who treat them, there are three main benefits to this new class of drug. One is that while biologics must be administered through injection or infusion, JAK inhibitors are small-molecule medications that can be taken orally, either once or twice a day.

The second main benefit is cost. While Pfizer has not released any information regarding how much tofacitinib will cost per dose, it most likely will be less than biologics. This is because biologics are produced from live organisms, resulting in a complicated and costly manufacturing process and an estimated price tag of $12,000 to $30,000 a year. JAK inhibitors, however, are small-molecule medications that do not require as complex a manufacturing process.

JAK inhibitors will compete for sales with biologics such as adalimumab (Humira) and etanercept (Enbrel), both of which revolutionized RA treatment when they were first introduced. If tofacitinib is approved by the FDA by the end of this year, Citigroup has forecast that it will generate $800 million in worldwide sales in 2015.

Most importantly, this drug could provide relief for the 30 to 40 percent of people diagnosed with RA who are unresponsive to any of the drug treatments currently offered.

Who Would Get It?

Still, while Pfizer plans to make tofacitinib available to patients as soon as possible upon FDA approval, health care providers may be slow to prescribe it initially.

"I don't think patients who are on biologics will be switched, but they will capture a percentage of the biologic start market," says Dr. Baraf, who estimates that tofacitinib may cost around 15 percent less than current biologics. "That's where this drug will have impact. I think it is as important as any biologic, and it's potentially cheaper."

Although clinical trials have proved the efficacy of the drug, long-term side effects won't clearly be understood until tofacitinib has been on the market for several years.

The most common side effects during clinical trials included bronchitis, headache and gastrointestinal issues like nausea, vomiting and diarrhea as well as high cholesterol. There is also some concern over reports of lymphoma and an increased risk of infection such as pneumonia.

"There's no free lunch in terms of how we treat rheumatoid arthritis," Dr. Baraf says. "There are risks involved with everything we do, but I think it's an acceptable risk profile, and it's a very impressive safety profile."

Still, for many patients, the opportunity to take a pill daily rather than a shot or infusion of medication will far outweigh any risks the drug may bring.

So does tofacitinib approval mean more similar drugs heading our way in the future? The answer is maybe. There are at least two other JAK inhibitors moving through clinical trials; how they fare will determine if they make it to market.

Fostamatinib, an oral medication in a class called spleen tyrosine kinase (SYK) inhibitors, is currently in phase III trials as well.