Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the arteries in your lungs. It happens when these arteries become narrow or blocked, making it harder for blood to flow through them. This forces your heart to work harder to pump blood.
PAH is a long-term condition that can get worse over time. As the heart works harder, it may become weaker and less able to pump blood well. Many people notice symptoms such as shortness of breath, tiredness, chest pain, or swelling in the legs and ankles.
While there's no cure for PAH, your health care provider will work with you to create a treatment plan that fits your needs. Your plan may include medicines that relax or widen the blood vessels in your lungs to improve blood flow.
One option is Uptravi (selexipag). Uptravi is FDA approved to treat adults who have PAH to help delay the worsening (progression) of the condition and lower the risk of hospital stays related to PAH. It comes as an oral tablet and an injection given through a vein.
If you have PAH, you may be wondering how Uptravi works and what to expect during treatment. This article answers common questions about Uptravi for PAH.
Is Uptravi Right for Me?
To find out if Uptravi is right for you, your health care provider will look at your medical history, including the type of pulmonary hypertension you have, your symptoms, and your overall health.
Pulmonary hypertension is a general term for high blood pressure in the lungs. The types of PH are grouped into five categories, called World Health Organization (WHO) Groups. Uptravi is FDA approved to treat adults with pulmonary arterial hypertension (PAH), which is WHO Group 1.
Your health care provider will also consider your symptoms and how much they affect your ability to be active. PAH symptoms are rated according to the following WHO functional classes:
- Class I: You have no symptoms with ordinary activity.
- Class II: You feel short of breath or tired during normal activity, but you feel comfortable at rest.
- Class III: Even lighter activity causes shortness of breath or fatigue, but you feel comfortable at rest.
- Class IV: You have symptoms even while resting.
Uptravi tablets were shown to be an effective treatment for PAH in people who had WHO functional class II or III symptoms.
Uptravi may also be used for other conditions as determined by your health care provider. Uptravi is only approved for use in adults. It is not known if this medicine is safe or effective for children.
How Does Uptravi Work for PAH?
Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the lungs. It happens when the pulmonary arteries (the blood vessels that go from your heart to your lungs) become narrow or blocked. This increases the pressure inside the pulmonary arteries and forces your heart to work harder to pump blood to your lungs. Over time, the artery walls become thicker, making the space where blood can flow even more narrow.
People with PAH may have reduced levels of prostacyclin, a natural substance that normally helps keep blood vessels relaxed and open. Prostacyclin also plays a role in preventing the walls of blood vessels from thickening.
Uptravi works by acting like prostacyclin. When Uptravi attaches to a specific protein on cells, called the prostacyclin (IP) receptor, it sends a signal that helps blood vessels relax and widen. It also stops smooth muscle cells from growing too much, which can help slow the thickening of artery walls. Together, these actions lower blood pressure in the pulmonary arteries and make it easier for the heart to pump blood through them.
How Do I Take Uptravi?
The recommended starting dosage of Uptravi tablets is 200 micrograms (mcg) taken by mouth twice daily. Taking it with food may help prevent or lessen side effects. Uptravi tablets should be swallowed whole.
Your health care provider will likely increase your dose each week until you reach the highest dose you can tolerate, up to 1,600 mcg twice a day. If a higher dose causes bad side effects, your prescriber may lower it to the previous dose that you tolerated well.
A lower dosage of Uptravi may be recommended in certain situations. For example, if you have moderate liver problems, your health care provider will likely start you at a lower dosage (200 mcg once a day) and increase it more slowly as tolerated. Also, if you take certain other medicines, such as clopidogrel, your doctor may change your Uptravi dosage to once daily instead of twice daily.
Always follow your health care provider's instructions carefully, and let them know if you have side effects or trouble tolerating your Uptravi dose.
Uptravi also comes in an injectable form for people who are temporarily unable to take the tablets by mouth. It is given as an infusion into a vein.
How Was Uptravi Studied for PAH?
The effect of Uptravi on pulmonary arterial hypertension (PAH) was studied in a large clinical trial called GRIPHON. To join the study, adults had to have a confirmed diagnosis of PAH. They could not join if they were already taking a medicine for PAH that works the way Uptravi does (prostacyclin analog). The people in the study were randomly assigned to take either Uptravi or a placebo (a pill with no active medicine). Neither the people being studied nor their doctors knew which one they were taking.
During the study, people took Uptravi tablets or a placebo twice a day. The main goal of the study was to find out how many people died or had a PAH-related problem during treatment and within a week after their last dose.
The study included 1,156 adults with PAH. They were grouped by how much their symptoms affected daily activity, known as World Health Organization (WHO) functional class. Most people were in Class II (46%) or Class III (53%), meaning they had mild to moderate symptoms with activity. Very few were in Class I or IV.
The following information describes the people who took part in the study:
- The average age was 48 years.
- About 80% were female, and the rest were male.
- Most were White (75%), about 21% were Asian, and the rest were other races or not reported.
- The people in the study were from different regions of the world, including Asia (20%), Eastern Europe (26%), Western Europe and Australia (28%), North America (17%), and Latin America (10%).
- On average, people in the study had been diagnosed with PAH around 2.4 years before joining the study.
- More than half (58%) of them had PAH that was idiopathic (no known cause) or heritable (runs in families). The rest had PAH that was related to connective tissue disease (29%), congenital heart disease that had been surgically repaired (10%), or other causes (3%).
- At the start of the study, most (80%) people were already taking other standard PAH medicines. About 20% were not taking any medicine for PAH.
What Are the Main Benefits of Uptravi Based on Studies?
The main goal (primary endpoint) of the GRIPHON study was to find out how many people died or had a PAH-related problem during treatment or within a week after their last dose. To count as a PAH-related problem, a person had to have one of the following events:
- Hospitalization for PAH
- Worsening PAH that required a lung transplant or a balloon atrial septostomy (a procedure to improve blood flow to the lungs)
- Started a new advanced treatment, such as chronic oxygen therapy or certain injectable PAH medicines
- At least a 15% drop in walking distance on a six-minute walk test plus worsening PAH symptoms or the need for another PAH-specific medicine
Note that some people in the study could have had more than one event, such as being hospitalized and later needing other medicines. In this study, the researchers only counted the first event that happened for each person.
People in the placebo group took it for about 15 months (median of 63.7 weeks), while those in the Uptravi group took it for about 16 months (median of 70.7 weeks). (Median is the midpoint in a set of results.)
The study found that 27% of people on Uptravi had a major PAH-related event, compared to 42% of those taking a placebo. Uptravi reduced the risk of these events by 40%, showing that people taking Uptravi were less likely to have worsening PAH (as shown by their first major PAH-related event) during the study.
Of those who had worsening PAH, the most common first events were hospitalizations or other signs of disease progression:
- About 14% of people taking Uptravi were hospitalized for PAH, compared to 19% of those taking a placebo.
- Around 7% of people in the Uptravi group had other signs of disease progression (decreased distance they could walk in six minutes, along with worsening PAH symptoms, or they needed another PAH-specific medicine) compared to 17% in the placebo group.
Overall, the GRIPHON study showed that fewer people taking Uptravi died or had a PAH-related problem, compared with people taking a placebo. Keep in mind that your results may differ from study results.
Are There Other Potential Benefits of Uptravi Based on Studies?
Possibly, but added benefits are not clear from the study. Along with the main study goal, the GRIPHON study also looked at a secondary endpoint of how well people could exercise. Secondary endpoints can help provide more information about a medicine's possible benefits, but they are not the main goal used to prove how well a treatment works.
In the GRIPHON study, exercise ability was measured by the six-minute walk test, which measures how far a person can walk in six minutes. After 26 weeks, people taking Uptravi walked about 12 meters (nearly 40 feet) farther than those taking a placebo.
Keep in mind that experts typically consider walking at least 33 meters farther on the six-minute walk test to be a meaningful improvement in people with PAH. So the improvement seen with Uptravi in the study may not reflect a noticeable change in daily activity for everyone.
Individual results can vary. Talk with your health care team about the plan to monitor how well your PAH treatment plan is working.
How Long Was Uptravi Studied, and What Do We Know About Its Long-Term Effects?
Some people continued taking Uptravi after the main study ended, and the researchers followed them for several more years in what's called an open-label extension. This means everyone knew they were taking Uptravi. The median treatment time was three years. Among the 574 people who continued taking it:
- 92% were still alive after a year
- 85% were still alive after two years
- 71% were still alive after five years
- 63% were still alive after seven years
But this extended part of the study did not include a placebo group for comparison. So the findings cannot tell us whether Uptravi itself affected survival over the long term.
If you have questions about long-term effects of Uptravi, talk with your health care provider.
How Can I Get Uptravi? Can I Get It at Any Pharmacy?
Uptravi requires a prescription from a health care provider. It is a specialty medicine. Your local pharmacy does not carry it. Instead, your health care provider will send your prescription to be filled by a specialty pharmacy. The specialty pharmacy will make arrangements with you to ship the medicine to your home.
Is There Any Cost Assistance Available?
A cost assistance program is available from Johnson & Johnson, the maker of Uptravi. It may reduce the amount you pay. Whether you qualify to enroll may depend on what type of insurance you have or if you are uninsured. Visit this website from the drugmaker for more information about Uptravi costs and copay savings.
You can also contact the drugmaker at 866-228-3546 to connect with a representative for financial support information and other resources.
