Photo Credit: Polesnoy
A panel of experts discuss the process of diagnosing paroxysmal nocturnal hemoglobinuria, as well as the impact of complement-inhibiting drugs on patients’ QOL.
Since 2007, complement-inhibiting drugs have enabled people with paroxysmal nocturnal hemoglobinuria (PNH) to live longer, more normal lives.
In the first of this two-part series, Physician’s Weekly (PW) spoke with Elizabeth Bowhay-Carnes, MD, Ryotaro Nakamura, MD, and Roy E. Smith, MD, who were not involved in the study, about the impact of complement-inhibiting drugs on patients’ QOL.
PW: How are these drugs improving the lives of people with PNH?
Dr. Bowhay-Carnes: Prior to the approval of these agents, patients needed red blood cell transfusions to survive, and a small subset was able to get bone marrow transplants. PNH itself causes anemia, a weakened immune system, and blood clots. Patients are at risk of dying from complications due to anemia, bone marrow failure, infections, and especially blood clots.
Newer-generation drugs are more effective at decreasing hemolysis, so people have close to normal hemoglobin levels, which leads to improved cardiac function, fewer symptoms, and overall improved health. They also offer different formulations, including an at-home subcutaneous injection twice per week and oral agents. All of these require less frequent clinic visits.
Dr. Smith: It largely depends upon the presentation. For example, a patient with PNH who presents with bone marrow failure is a candidate for a bone marrow transplant or immunotherapy. For patients presenting more typically—with significant, continuous, or intermittent hemolysis with the red blood cells destroyed intravascularly and sometimes extravascularly—the newer, almost revolutionary therapies inhibit the complement pathway, so red cells are not destroyed. Patients have less fatigue, less severe anemia, fewer complications associated with anemia, and a lower risk for a thrombotic event.
Do comorbidities determine which PNH treatment is best?
Dr. Smith: They can. For example, if a person has an active infection, some of the newer therapies that inhibit the complement cascade can predispose people to major infections with encapsulated bacteria. So, you would not want to treat someone with an active infection with a complement inhibitor.
Likewise, suppose a person with PNH has a history of thrombotic events or has an active thrombotic event and a bleeding disorder, such as a bleeding peptic ulcer. In that case, you may not want to treat them with anticoagulation. The kidneys excrete many drugs, so if kidney function is abnormal, we may need to adjust the dose or discontinue its use.
A patient may have an allergic reaction to a drug.
What complications and adverse effects need to be considered?
Dr. Nakamura: These drugs are generally well tolerated with minor side effects such as mild headache or itching. However, because PNH drugs decrease the function of the complement system, which is important in fighting certain infections, infection with certain types of bacteria can be serious. Patients are advised to receive vaccinations against organisms including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.
Dr. Bowhay-Carnes: Due to infection risk, some patients are required to be on penicillin long-term, and all patients are counseled to call their doctor immediately if they have a fever.
Dr. Smith: Renal failure in patients with untreated PNH can be significant. The disease itself can cause multiple complications, including overwhelming hemolysis and thrombotic events in unusual sites such as the portal vein or the brain. Patients can also develop significant frustration and depression.
What are some barriers to care?
Dr. Bowhay-Carnes: All these drugs are still very expensive, and navigating that process is complex. Because PNH is fatal and there are no other options, insurance companies pay for one of the four drugs. But it takes a lot of paperwork.
Dr. Nakamura: PNH is a very rare disease, even for practicing hematologists. Access to a center of excellence and PNH experts may be difficult for some patients who live far from large medical centers.
Dr. Smith: Making the diagnosis. PNH is a great masquerader. People often complain of pain, migraine headaches, horrible fatigue, muscle dystonia, gastrointestinal issues, anemia, thrombotic events, and kidney problems. They present to various doctors: nephrologists, hematologists, gastroenterologists, or family practitioners. Each specialist looks at the disease in their own limited way and can miss the overall disease.
Consider PNH in your differential diagnosis. Clinicians have heard of the disease in medical school or elsewhere, but very few of us have seen people with the disease.
The drugs are very expensive. Costs vary but may be up to half a million dollars per year for life, with extraordinary patient copays.
Insurance companies are responsible for ensuring that the money they spend is well spent, and they are careful. So, there is often a disagreement between the physician and the insurance company regarding whether a patient is covered for a given treatment. Often, an insurance company will approve an established drug instead of a newer drug that may be better and more convenient for the patient.
Look for more from Dr. Bohway-Carnes and colleagues in part two, where they’ll discuss the management of paroxysmal nocturnal hemoglobinuria in older patients.
