ERS Adds Sotatercept to Pulmonary Arterial Hypertension Treatment Guidelines

The European Respiratory Society (ERS) issued a focused update to its guidelines for treating pulmonary arterial hypertension (PAH), formally recommending the activin signaling inhibitor sotatercept (Winrevair; Merck & Co.) as an add-on therapy for many patients already receiving background treatment. For pharmacists, the change is significant: It introduces a first-in-class biologic with a distinct adverse event (AE) profile, new monitoring demands, and counseling needs that differ significantly from the oral and infused therapies that have long defined PAH management.¹

What’s New in the Guidelines?

The 2022 ESC/ERS guidelines built PAH pharmacotherapy around 3 established pathways—the endothelin pathway, the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO-sGC-cGMP) pathway, and the prostacyclin pathway—using a multiparametric risk assessment to guide initial combination therapy and sequential escalation with agents such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, riociguat (Adempas; Bayer), and prostacyclin analogues. The 2026 update intends to extend the framework, not replace it. Sotatercept targets a fourth pathway, acting as a fusion protein that rebalances pro- and antiproliferative signaling implicated in pulmonary vascular remodeling.^1,2

The Task Force issued a strong recommendation, backed by high certainty of evidence, for add-on sotatercept in patients with PAH who are already receiving PAH drugs and are at intermediate-low, intermediate-high, or high risk of death during follow-up. For patients at low risk, the panel declined to make a recommendation, citing low certainty of evidence and the small number of such patients enrolled in trials.¹

The Evidence Base for the Updated Guidelines

The recommendation rests on 4 randomized controlled trials—PULSAR (NCT03496207), STELLAR (NCT04576988), ZENITH (NCT04896008), and HYPERION (NCT04811092). In the pivotal phase 3 STELLAR trial, adding sotatercept to stable background therapy improved 6-minute walk distance by 40.8 m versus placebo (95% CI, 27.5-54.1; P < .001), a result that supported FDA approval of the agent in March 2024.^1,3,4

Across the pooled analysis, the panel reported a relative risk for hospitalization of 0.19 (95% CI, 0.09-0.42) and a relative risk for clinical worsening of 0.28 (95% CI, 0.21-0.38), favoring sotatercept.¹

Key Guidance for Pharmacists: Monitoring the New Agent

Sotatercept is dosed subcutaneously with a starting dose of 0.3 mg/kg and a target dose of 0.7 mg/kg, dosing that carried through STELLAR and the later trials into clinical practice. Because it is administered by injection every few weeks rather than taken orally, pharmacists can help educate patients on administration, storage, and adhering to the follow-up schedule.¹

Increased hemoglobin (described in 5.5%–12.8% of patients on sotatercept in trials) and thrombocytopenia (6.1%–12.8%) are the most common hematologic AEs. The guideline notes these may require treatment interruption or dose modification, per the summary of product characteristics. Pharmacists reviewing lab trends are well positioned to flag rising hemoglobin or falling platelets before they become clinically consequential.¹

Bleeding, Telangiectasia, and Drug Interactions

Bleeding events were reported in 21.5% of patients on sotatercept versus 12.5% on placebo, with epistaxis the most frequent form. In the SOTERIA long-term trial (NCT07218029), severe bleeding occurred in 5.2% of patients and was associated with concomitant oral anticoagulation in roughly half of cases—a concrete interaction check for pharmacists reconciling medications.^1,5

A key clinical pearl for pharmacists is to watch the anticoagulation gap. Because severe bleeding on sotatercept was frequently tied to concurrent oral anticoagulation, medication reconciliation should specifically surface anticoagulant use, and counseling should prime patients to report nosebleeds, unusual bruising, or bleeding that does not stop. Telangiectasia, which was seen in approximately 10.4% of trial patients, is another visible sign worth normalizing in counseling so patients report rather than discontinue on their own.¹

A Second Change: Follow-Up Catheterization

The update also addresses right heart catheterization (RHC) during follow-up, conditionally suggesting it for patients at intermediate-low, intermediate-high, or high risk when a therapeutic consequence is expected—for example, before escalating or deescalating therapy, or in specific subgroups such as patients with congenital heart disease or portal hypertension being evaluated for transplantation. This recommendation carries very low certainty of evidence.¹

Because sotatercept’s long-term effects on the right ventricle remain incompletely understood, the guideline stresses that patients be followed in specialized PH centers and that all potentially related AEs be reported in line with good pharmacovigilance practice—an area where pharmacists are natural partners.¹

REFERENCES

1. Kovacs G, Zeder K, Humbert M, et al. European Respiratory Society clinical practice guidelines update for the treatment of pulmonary arterial hypertension. Eur Respir J. 2026;2601178. doi: 10.1183/13993003.01178-2026

2. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2022;61(1):2200879. doi:10.1183/13993003.00879-2022

3. Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558

4. FDA approves Merck’s WINREVAIR (sotatercept-csrk), a first-in-class treatment for adults with pulmonary arterial hypertension (PAH, WHO* Group 1). News release. Merck. March 26, 2024. Accessed September 8, 2026. https://www.merck.com/news/fda-approves-mercks-winrevair-sotatercept-csrk-a-first-in-class-treatment-for-adults-with-pulmonary-arterial-hypertension-pah-who-group-1/

5. Preston IR, Badesch D, Ghofrani H, et al. A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA. Eur Respir J. 2025;66(1):2401435. doi:10.1183/13993003.01435-2024