by Phyllis Hanlon, Contributing Writer

Recent studies report that the future in health care lies in personalized medicine. Personalized medicine is a developing field of health care that takes into account individual clinical, genetic, environmental, behavioral and other factors in treating disease. This approach has been used successfully in some medical fields already, including oncology and pulmonology, specifically for cystic fibrosis. In late August 2017, personalized medicine took another step forward with the U.S. Food & Drug Administration approval of tisagenlecleucel (Kymriah®) for certain pediatric and young adult patients with acute lymphoblastic leukemia. Tisagenlecleucel is the first gene therapy approved in the U.S. that uses genetically modified cells from the patient’s own immune system, and “teaches” them to recognize, target, and kill cancerous cells.

In WHO Group 1 PH (PAH, pulmonary arterial hypertension), treatment with calcium channel blockers can be considered a form of “personalized medicine,” as the therapy is very effective in a small number of patients who respond positively to a test done during the right heart catherization called an acute vasodilator test. Since this discovery several decades ago, no big strides have been made in individualized, personalized treatments for patients with any forms of PH. Drugs are approved based on average treatment response in a group of patients studied in a clinical trial, and clinicians still prescribe therapy based on expert recommendations and the severity of a patient’s disease. To dive deeper, two researchers conducted a review and looked at what is already known about response to PAH-related medication, how clinicians identify “super responders” to these therapies and what the future might hold for personalized medicine in PAH patients. (

Stephen J. Halliday, M.D., and Anna R. Hemnes, M.D., both of Vanderbilt University Medical Center, noted that patients with PAH have historically had “dismal” survival, some as low as three years when untreated. During the last quarter century, however, research has brought 14 FDA-approved medications in five different classes to market, substantially improving survival and quality of life.

The medications used to treat PAH that were included in this review were:

  • Calcium channel blockers (CCB)
    • g., diltiazem and amlodipine
  • Endothelin receptor antagonists (ERAs)
    • g., ambrisentan, bosentan, and macitentan
  • IP prostacyclin receptor stimulators
    • g., selexipag
  • Phosphodiesterase type 5 inhibitors (PDE5)
    • g., sildenafil and tadalafil
  • Prostacyclin analogues
    • g., epoprostenol, iloprost, and treprostinil
  • Soluble guanylate cyclase stimulators (sGC)
    • g., riociguat

Drs. Halliday and Hemnes pointed out that not enough research has been done to predict how patients will respond to these drugs. In the clinical trials for each of these medications, scientists observed that some types of patients could be more likely to respond to a therapy than others. For example, one study Drs. Halliday and Hemnes included in their analysis shows that men might be more likely to respond positively to tadalafil than women; another study shows that, when ambrisentan and bosentan are analyzed together, women might be more likely to respond positively to an ERA than men. These are only observations though, and require further study to verify the findings. It also does not mean, for example, that women should not be on tadalafil or that an ERA will not work in men.

They explained that when researchers conduct a clinical trial to find out how effective a drug might be, they must look at all the patients enrolled in the trial. Average changes in survival, disease progression or six-minute walk distance (6MWD) have been viewed as important factors by the FDA when deciding to approve a new drug. Not all patients will have the same response, however. Across the study population some will have little or no response, while others respond particularly well and are referred to as “super responders.”

Currently, many clinicians follow expert consensus guidelines when treating patients with PAH. Once they have arrived at a definite diagnosis, they determine into which World Health Organization (WHO) functional class (FC) the patient falls and then select a drug or combination of drugs recommended for that diagnosis and class. “The evidence to guide clinicians in this vital decision is limited at present,” although most clinicians do recognize that some patients have an extremely positive response to treatment (i.e., the “super responders”), according to the authors.

Drs. Halliday and Hemnes reported that PAH behaves differently in every patient and a more “…personalized approach to therapy is needed…” They suggested that patients who have an extraordinary response to treatment be examined more closely to learn and understand this response, which could help other patients in the future. They asserted that advances in precision medicine and genetic testing could help determine which drug is best for which patient. One of the first steps toward this goal is more specifically defining what makes a “super responder,” which might involve several clinical observations, lab tests and heart and blood flow measurements after the patient has started taking a drug. By identifying “super responders” and learning more about them, clinicians can then identify which therapies might be best suited for similar patients before they begin treatment, the authors suggested.

“We are entering an era of precision medicine, one in which algorithm-based treatment approaches will be modified in ways that take individual variability into account,” the authors wrote. Using the same treatment for every patient will not always achieve the best outcome; treatment tailored to the individual will result in optimal outcomes.

Each PH patient is different. It is essential that you talk to your own doctor about what treatment options are best for you. For more information on finding a doctor or an accredited care center, visit



Not all patients have the same response, or even any response, in clinical trials. People who respond particularly well, however, are called “super responders.”

Two researchers are looking at factors including how these “super responders” are defined for clues into what the future might hold for personalized medicine in PAH patients.

PAH behaves differently in each patient and a more personalized approach to treatment could improve care.