When educating patients with paroxysmal nocturnal hemoglobinuria (PNH), it is important to review the available treatment options and discuss individual considerations, such as day-to-day lifestyle needs, tolerability, and cost, to identify the best-fit therapy for each patient.

The first question when considering personalizing treatment goals in PNH is: Does the patient truly require treatment? Because once treatment starts, it often never ends. For patients with asymptomatic classical PNH, a small clone size (usually less than 20%), and minimal anemia, one can consider just observation. It is almost like a smoldering PNH. You can consider watching and waiting in these patients. There are some data suggesting that these patients are less likely to develop blood clots. As a clinician, one of the biggest concerns with observation is the uncertainty about when a blood clot might occur, so you want to follow these patients closely and start treatment when needed.

If patients with PNH are symptomatic, then usually their hemoglobin level is less than 10 g/dL, they are short of breath, they may have cardiopulmonary symptoms or smooth muscle problems, and/or they already have a blood clot. Certainly, in these patients, it is fair game to initiate therapy. There are more US Food and Drug Administration (FDA)–approved drugs for PNH than there are for many other rare diseases, so the management of PNH can be more of an art than a science because there are multiple effective therapy choices. I would say that, as a clinician, treatment preferences may be provider dependent based on experience. We also factor in patient preference, whether it is regarding the route of delivery (ie, injectable, intravenous, or oral), cost, insurance, or potential side effects.

I typically recommend starting with C5 inhibitors. I often begin with ravulizumab because of convenience, as it can be given every 8 weeks and it stays in the body for a longer period. I will switch or add proximal complement inhibitors if the patient remains symptomatic, their hemoglobin level is less than 12 g/dL, and they complain of symptoms such as fatigue. Then we talk about switching to proximal complement pathway inhibitors, such as iptacopan or pegcetacoplan, or adding danicopan. Adding danicopan to C5 inhibitor therapy adds to the cost because there are 2 drugs now instead of 1, but the patient can take comfort in having full coverage, especially during periods of inflammation such as infection or surgery.

Allowing for shared decision making and incorporating patients into the decision-making process do take more time because you need to explain all the available treatment options. Therapeutic options include infusions, pills, self-injections, or a combination. You talk with patients about the pros and cons of injections vs oral therapies for them, and about what happens if they miss a dose. I also remind patients that they can start with one and switch if it is not the right therapy for them; they do not “burn any bridges” by choosing one therapy over another.

We are very fortunate to have so many therapy options for PNH. With all of our advancements, the life span for a treated patient with PNH is now approaching that of the non-PNH population. What would excite me the most for the future is a cure—a finite therapy, such as gene therapy, where you do not have to take any of these drugs forever.