People with moderate to severerheumatoid arthritis (RA)who haven’t responded well to one or more tumor necrosis factor (TNF) inhibitor medications now have a new option. The U.S. Food and Drug Administration (FDA) recently approved baricitinib (Olumiant), a pill that is taken once a day.
Baricitinib is a targeteddisease-modifying antirheumatic drug (DMARD)that blocks Janus kinase (JAK), a group of enzymes that enable inflammatory signals to be activated inside a cell. It’s the second in this class of drug to hit the market for the treatment of RA; tofacitinib (Xeljanz) was the first, approved in 2012.
“It’s not a biologic but a ‘small molecule,’ or oral, targeted agent, that is highly effective in treating the signs and symptoms of RA,” explains Paul Howard, MD, a rheumatologist in Scottsdale, AZ. It is expected to be significantly cheaper than biologic medications.
Safety Concerns
Baricitinib maker Eli Lilly and Company had sought approval for both a 2 mg dose and a 4 mg dose, but the FDA approved it at the end of May 2018 only at a 2 milligram (mg) dose. The agency expressed concerns about cases of deep vein thrombosis (DVT) in clinical trials in patients taking the 4 mg dose. DVT is a blood clot that forms in a deep vein, usually in the leg. It can cause swelling, redness and pain, and can break loose and travel to the lung, which can be fatal.
Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, in Fargo, was on the FDA Arthritis Advisory Committee when it considered Eli Lilly’s application for baricitinib in late April. He voted for approval of the 2 mg dose and against approval of the 4 mg dose.
“There weren’t enough patients [in the trials] on either dose to be sure of the real rate of deep vein thrombosis, but the best conclusion we could arrive at is the 2 mg dose provided most of the efficacy of the 4 mg dose and probably less of the deep vein thrombosis risk,” Miller explains.
Baricitinib will carry a boxed warning about the risk of thrombosis (blood clots) as well as serious infections and malignancies. Its main competitor,tofacitinib(在申请的两种剂量中也被批准了较低的剂量)，带有类似的方框警告，减去血栓警告。
礼来公司免疫学副总裁皮特·萨尔兹曼医学博士说:“这是一个重要的潜在风险，医生们需要意识到，我们将对医生进行相关教育。”“风湿病学家非常清楚如何识别血栓风险增加的患者，以及如何持续监测。我们认真对待这种教育。”
Dr. Salzmann says the 4 mg dose is approved in other countries, and Eli Lilly will continue to try to get it approved here, too. “We are working with the FDA to define a path for potential approval of the 4 mg in the U.S.,” he says.
Experts say the overall market for baricitinib might be small, because it was approved for patients who have failed at least one TNF inhibitor, but Dr. Salzmann says those patients need options. “This is a group that physicians tell us has the highest unmet need. Those who have failed anti-TNFs are the most challenged getting to a good clinical outcome,” Dr. Salzmann says.
Convenience Factor
One benefit of using this drug is that it’s taken orally once a day; by contrast, TNF inhibitors and other biologics are either injected or infused as often as once a week. JAK inhibitors, including baricitinib, “are orally active, not injectables, which is a very nice option,” says David Pisetsky, MD, rheumatologist and professor of medicine at Duke University Medical Center in Durham, NC. “There are many patients who don’t want injections or infusions, so there is a convenience with a one-a-day pill that many would welcome.”
Price will likely be another selling point. Eli Lilly says bariticinib’s annual cost will be $24,930 – Dr. Salzmann says that’s 60 percent less than the leading TNF inhibitor. But the final price a consumer pays depends on many factors, including insurance coverage.
In terms of efficacy, Dr. Salzmann says that in studies, improvements in symptoms were seen as early as one week. “Rapid symptom relief, particularly for patients who have failed one or more therapies, is something they are anxious and excited about. That is a benefit,” he says.
Comparing Drugs
There have been no head-to-head studies comparing baricitinib with tofacitinib. Although they are both JAK inhibitors, Dr. Pisetsky says they do have differences.
“There are a number of enzymes in the JAK family that are inhibited by JAK inhibitors. These two medications inhibit one enzyme in common, but each inhibits another enzyme that is different,” he explains. “It’s not entirely clear if these differences for RA would make that much of a difference in efficacy. Are there patients that will respond to one JAK inhibitor rather than another? Time will tell.”
FDA表示，患者不应将baricitinib与其他JAK抑制剂、生物制剂或强免疫抑制剂(如dmard硫唑嘌呤和环孢素)联合使用，尽管它可以与甲氨蝶呤和某些其他dmard联合使用。
Eli Lilly says it will launch baricitinib in the U.S. this month.
Author: Jennifer Davis
Related Resources:
- RA Research Briefs: Tofacitinib, Fish, Remission
- Research Identifies Which RA Patients May Successfully Reduce Their Biologics
- Rheumatoid Arthritis Treatment