Oral JAK Inhibitor's Clinical Place To Be Determined

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

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. 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.

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.

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

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. 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.

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.

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

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. 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.

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.