And then there is cost.
The JAK inhibitor will be expensive, just as the currently available biologic agents are. Pfizer has said that the recommended regimen of one 5-mg tablet twice a day will be priced at $2,000 a month, according to Dr. Matteson, chair of rheumatology and professor of medicine at the Mayo Clinic Medical School in Rochester, Minn. He noted that Pfizer is already offering a program to help patients cover their share of the copayment for the new drug.
Dr. Karmela K. Chan
Dr. Chan said that "without a doubt the cost will be an issue for patients. Cost of drug, side effect potential, efficaciousness, and convenience all factor into patients’ decisions.
"Also, yes, in our practice, I have been told multiple times that I could make more money if I put more people on infusions. We can buy and bill so we make more money that way, plus we make money off just the service of the infusion. But I think this issue of making money from infusions will perhaps not pass muster too much longer for the following reasons: Ethical physicians won’t infuse just to infuse (one would hope), and I think in the coming years fewer insurers will allow buy and bill. On top of that, I am not sure if Medicare reimbursement rates for the infusion service will change."
Dr. Matteson noted that the drug, to be marketed as Xeljanz, has shown efficacy compared with placebo in a number of studies considered by the Food and Drug Administration (FDA). The drug inhibits the protein kinase, which is important in cell-to-cell interaction and may be how the drug acts to decrease inflammation.
Only time will tell whether that decrease in inflammation will translate into reduced joint damage in RA patients or even into decreased risk for extra-articular manifestations of the disease, including cardiovascular disease, lung disease, and eye disease.
Dr. Eric L. Matteson
Treatment with anti–tumor necrosis factor (anti-TNF) drugs has been shown to lower the risk for cardiovascular disease associated with RA. But it took 5 years of post-marketing surveillance before rheumatologists began to recognize that benefit. Any similar effect with the JAK inhibitor may take just as long to become apparent, said Dr. Matteson.
In order to detect any effects, the FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a post-marketing study, according to the FDA’s statement announcing the approval.
Dr. Matteson noted that safety and efficacy trials of the drugs showed that two common side effects were headaches and diarrhea, severe enough to cause the patient to discontinue the drug.
Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.
Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.
The post-marketing study will compare two doses of tofacitinib with another approved treatment for RA.
At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.
Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.