Sotatercept in ERS PAH Guidelines: What Pharmacists Should Watch

In an interview with Pharmacy Times, Vallerie McLaughlin, MD, professor of internal medicine at the University of Michigan School of Medicine, discussed the 2026 European Respiratory Society (ERS) guideline update incorporating sotatercept (Winrevair; Merck) into the pulmonary arterial hypertension (PAH) treatment algorithm. McLaughlin said, going forward, she expects that combination and quadruple therapy will be part of PAH treatment. For pharmacists, McLaughlin outlined key monitoring considerations, including hemoglobin and platelet changes, bleeding risk, and postmarketing reports of pericardial effusion and intrapulmonary shunting. She added that the recent FDA label update based on HYPERION trial data supports earlier intervention within the first year of diagnosis.^1,2

Pharmacy Times: What should pharmacists watch for when patients start sotatercept alongside background PAH therapy?

Vallerie McLaughlin, MD: Much of the side effect profile of sotatercept is well documented and consistent from the clinical trials, and then, of course, as the drug gets used in thousands rather than hundreds of patients, we're seeing other side effects. The most common side effects from the clinical trials were an increase in hemoglobin and reduction in platelet count in terms of the hematologic effects, and that is something that needs to be monitored. The FDA requires a complete blood count (CBC) prior to each of the first 5 doses, and sometimes we need to get CBCs further into the course. There are clear algorithms for dose reduction or interruption based on the changes in hemoglobin and hematocrit. In my clinical practice, that's all very manageable. We don't really run into too many problems with that. It's very rare that we have to stop the drug, although sometimes we have to go down on the dose.

Other common side effects noted in the clinical trials include telangiectasias, which are generally more cosmetic, and I have not found that to be problematic. Probably the most concerning side effect from the clinical trials that we have to be very careful about and counsel the patient on is the risk of bleeding. Nearly 40% of patients in the clinical trial had some bleeding. It was most commonly epistaxis, so nosebleeds—most commonly not serious, although there are some patients who have more serious bleeding, and this is something that we need to follow very carefully in clinical trials. Sometimes we need to reduce the dose. We've had some patients with very serious bleeds that we've had to stop the medication on. It's very important to follow that.

And then there are a couple of other side effects that have been described postmarketing. One is the pericardial effusion. It's very interesting that that was not seen in the clinical trials, and in fact, all 3 of the phase 3 trials had echoes at the beginning and end of 24 weeks, and there was not really a shift in pericardial effusion. But there are several case series that have described pericardial effusions, some of which have been serious, and some of which have required intervention. It seems to happen more commonly in patients with connective tissue disease, so this is something that needs to be monitored in clinical practice.

And then the other side effect that has been described postmarketing is intrapulmonary shunting—so essentially, blue blood from the right side crossing to the left side without getting through the lungs, causing a reduction in oxygen saturation. This is seen as delayed contrast bubbles on an echocardiogram, and sometimes these patients can get very hypoxemic. This is something that we now routinely monitor for. We do a contrast echo before we start and then routinely after we start, and of course we monitor the oxygenation. And we've seen this in clinical practice. Sometimes we need to reduce the dose of sotatercept in these patients. Oftentimes we see this, but it doesn't have clinical consequences—the patient doesn't get hypoxic, and we just follow it. But those are the most important things to follow.

Pharmacy Times: Where do you see PAH treatment heading now that a fourth pathway is in the guidelines?

McLaughlin: I think it's been a huge advance for PAH treatment. I think for initial therapy, we have such great data on combination oral therapy that a large majority of patients will start there. But if they don't improve, if we don't get them to low-risk status, sotatercept is now placed higher in the guidelines, where it's often the next agent that we add—so the third agent that we have. And of course, the prostacyclins are still important, but I see us using more combination therapy that includes sotatercept because of its very marked hemodynamic effects and improvements in RV functioning. It's good that we have 4 pathways for patients who don't meet our goals, so I think combination therapy and quadruple therapy will be part of our treatment.

Pharmacy Times: Is there anything else you wanted to add, possibly about sotatercept’s recent label update?

McLaughlin: I assume that was based on HYPERION, the data that we have now within the first year of diagnosis, and again, I think that supports the earlier intervention and the potential to modify the disease. And HYPERION was a very positive study, even though it was stopped early due to loss of clinical equipoise. I think the totality of the evidence with sotatercept now—again, across the different patient populations, prevalent, high risk, and first year of life, across the different clinical measures, improvement in exercise tolerance, hemodynamics, RV function, and biomarkers—makes for a very solid case that this should be part of the treatment of most of our patients with pulmonary arterial hypertension.

REFERENCES

1. Halpern L. ERS adds sotatercept to pulmonary arterial hypertension treatment guidelines. Pharmacy Times. Published September 16, 2026. Accessed September 23, 2026. https://www.pharmacytimes.com/view/ers-adds-sotatercept-to-pah-treatment-guidelines

2. Halpern L. FDA approves sotatercept-csrk label update for early PAH use. Pharmacy Times. Published September 22, 2026. Accessed September 23, 2026. https://www.pharmacytimes.com/view/fda-approves-sotatercept-csrk-label-update-for-early-pah-use