History, investigation, findings, and initial treatment
A 61-year-old female with a >20-year history of connective tissue disease–related pulmonary arterial hypertension (CTD-PAH) was admitted in June 2025. Despite being on triple therapy for PAH as well as prednisolone and cyclophosphamide for systemic lupus erythematosus (SLE), her PAH remained uncontrolled.
In 1991, at age 27, the patient was diagnosed with SLE. (Figure 1) She initially presented with arthritis, serositis, cerebral lupus, vasculitic ulcer, proteinuria, and Raynaud’s phenomenon. Laboratory tests showed markedly elevated antinuclear antibody (ANA) titre of >1:320, anti–double stranded DNA (anti-dsDNA) of >4,000 U/mL, and presence of anti-RNP and anti-Ro antibodies. She was started on high-dose prednisolone and monthly intravenous cyclophosphamide for 6 months.
Four years after SLE diagnosis, the patient developed new-onset pulmonary hypertension (PH) during an SLE flare in 1995. Her WHO functional class (FC) was II. Echocardiography revealed a severely elevated pulmonary artery systolic pressure (PASP) of 95 mm Hg.
The patient was given another course of prednisolone and cyclophosphamide. Calcium channel blocker was the only available treatment option for PAH during that time. Diltiazem 60 mg TDS was added. (Figure 1) Subsequently, her PASP decreased to 60 mm Hg in 2001 and normalized at 35 mm Hg in May 2002.
In August 2002, she developed shortness of breath (SoB), with PASP rising to 90 mm Hg while SLE was inactive. Right heart catheterization (RHC) revealed a mean pulmonary artery pressure (mPAP) of 43 mm Hg, pulmonary vascular resistance (PVR) of 7 WU, and no vasodilator response, confirming a diagnosis of CTD-PAH. As PAH-targeted treatment was limited then, she continued to receive diltiazem.
Treatment with triple PAH therapy
In 2006, the patient received sildenafil 20 mg TDS, which was uptitrated to 80 mg TDS in 2009. (Figure 1) From 2007 to 2020, she was in WHO FC I, with PASP in the range of 70–90 mm Hg. She declined 6-minute walk test due to knee pain, and N-terminal pro- B-type natriuretic peptide (NT-proBNP) testing was not available at that time.
In 2021, she reported SoB, and her WHO FC worsened to II; her 6-minute walk distance (6MWD) was 355 m, and NT‑proBNP (tested in the private sector) was 506 pg/mL. Macitentan was therefore added in March 2022, which led to a reduction of NT-proBNP to 230 pg/mL, but 6MWD remained static. (Figure 1)
Between 2023 and 2025, the patient was hospitalized three times.
In January 2023, she was admitted due to SoB. Her 6MWD during hospitalization was 371 m. (Figure 1) COMPERA 4-strata risk assessment showed intermediate–low risk. Echocardiography showed interval worsening of right ventricular systolic pressure (RVSP) with mild right ventricular systolic dysfunction. Repeat RHC in October 2023 revealed mPAP of 60 mm Hg and PVR of 14 WU. Consequently, the patient was started on selexipag 200 mcg BID in November 2023 and placed under joint care with the cardiology department. In February 2024, 6MWD and NT-proBNP worsened despite dose escalation of selexipag to 600 mcg BID. (Figure 1)
In April 2024, she was readmitted due to fluid overload and severe oxygen desaturation, requiring 10 L/min of supplemental oxygen, dopamine support, and inhaled iloprost. Her 6MWD was 284 m. (Figure 1) Selexipag was optimized to 1,600 mcg BID in July 2024.
However, her response to the maximally tolerated dose of triple PAH therapy was suboptimal. Repeat echocardiography in May 2025 showed interval worsening of mPAP, right ventricular pressure overload, a moderately to severely dilated right ventricle, pulmonary artery dilatation, and pulmonary regurgitation. (Table) In June 2025, she was readmitted due to right heart failure symptoms and desaturation.
Apart from ankle oedema, the patient experienced profound oxygen desaturation (arterial oxygen saturation [SaO2], 85 percent on room air) and required high-flow nasal cannula, placing her in WHO FC III. Additionally, her NT-proBNP surged to 4,259 pg/mL in June 2025. In June 2025, her 6MWD further deteriorated to 138 m on 3 L/min long-term oxygen therapy (LTOT) — the lowest during her treatment course. (Figures 1 and 2) Her REVEAL Lite 2 risk score was 10, indicating a high 1-year risk of death. A course of inhaled iloprost was provided.
Treatment with sotatercept
In August 2025, the patient was discharged with 3 L/min LTOT and referred to Grantham Hospital for lung transplant evaluation. After weighing risks and benefits, transplant was considered unrealistic, and she chose to continue medical therapy, being aware of the high-risk nature of her condition.
Through a named patient programme, the patient received the first subcutaneous (SC) dose of sotatercept at 15 mg Q3W on 18 August, the second dose at 32 mg on 9 September, and the third dose at 32 mg on 30 September 2025. (Figure 1)
After three injections of sotatercept, the patient demonstrated gradual clinical improvements. Her 6MWD improved from 138 m in June 2025 to 253 m in November 2025. (Figure 1). LTOT was reduced from 3 to 2 L/min. Moreover, her NT-proBNP level dropped from 4,259 pg/ mL in June 2025 to 1,699 pg/mL (prehospitalization level) in November 2025. (Figure 2)
The patient’s haemoglobin (Hb) levels rose after sotatercept treatment. After three injections, her Hb rose from 12 to 14.7 g/dL. On 2 December 2025, Hb level normalized at 13.8 g/dL, and the fourth sotatercept dose was administered on the same day. Platelet counts remained normal throughout sotatercept treatment, and no other adverse events (AEs) were observed.
After seven doses of sotatercept, reassessment with echocardiography on 6 February 2026 showed interval improvements in haemodynamic parameters, including mPAP, right ventricular dilatation, and systolic function. (Table) On 20 February 2026, the patient’s NT-proBNP level stabilized at 1,652 ng/L. (Figure 2)
On 24 February 2026, the patient received her eighth dose of sotatercept. Notably, her WHO FC improved from III to II. She reported less SoB, better exercise tolerance, and ability to tolerate 20 minutes of exertion. LTOT was reduced from 2 to 1 L/min at home, while SaO2 remained above 95 percent. She also attempted a few hours without oxygen supplementation at home, which resulted in SaO2 of around 93–94 percent. (Figure 1)
The latest RHC was performed on 5 March 2026, showing improvements in both mPAP (39 vs 60 mm Hg) and PVR (9.63 vs 14 WU) compared with RHC findings in 2023. (Table)
Last seen on 11 March 2026, her latest 6MWD further improved to 266 m. (Figure 1)
Discussion
CTD-PAH, including SLE-PAH and systemic sclerosis–associated PAH (SSc- PAH), is the second most prevalent PAH subtype after idiopathic PAH (IPAH).1 CTD-PAH is associated with worse survival outcomes vs IPAH.2 This underscores the need for close collaboration between rheumatologists and cardiologists.
In Asia, the leading cause of CTD-PAH is SLE. SSc-PAH is the predominant form of CTD-PAH in Western countries and is associated with the worst survival.3,4 The 2022 European Society of Cardiology/ European Respiratory Society (ESC/ERS) Guidelines recommend annual PAH evaluation in patients with SSc.1
CTD-PAH: Role of sotatercept
CTD-PAH treatment follows the same algorithm as other types of PAH, which emphasizes regular risk assessment and timely use of initial combination therapy.5 (Figure 3)
Conventional PAH therapies used in the last two decades primarily promote vasodilation by targeting the endothelin-1, nitric oxide, and prostacyclin pathways. A new treatment option targeting a fourth pathway is now available.6 Sotatercept, a first-in-class activin signalling inhibitor, received regulatory approval in Hong Kong in 2025. As a reverse remodelling agent, sotatercept does not merely act as a vasodilator. Instead, it restores the balance between antiproliferative and proproliferative signalling pathways.6,7 Sotatercept is recommended for PAH patients at intermediate–low, intermediate–high, and high risk, including our patient.5 (Figure 3)
STELLAR
The efficacy of sotatercept was evaluated in the phase III STELLAR trial, in which 323 adult patients with WHO FC II or III PAH (CTD-PAH, 14.9 percent) were randomized 1:1 to receive SC sotatercept (starting dose, 0.3 mg/kg of body weight; target dose, 0.7 mg/kg) or placebo Q3W. All patients received stable background therapy (triple therapy, 61.3 percent; prostacyclin infusion therapy, 39.9 percent; double therapy, 34.7 percent; monotherapy, 4.0 percent).8
Results showed significant improvements with sotatercept vs placebo in 6MWD (+40.8 m; 95 percent confidence interval [CI], 27.5–54.1; p<0.001), NT-proBNP (difference, -441.6 pg/mL; p<0.001) and WHO FC (29.4 vs 13.8 percent; p<0.05). With respect to the PAH-SYMPACT quality-of-life questionnaire, changes from baseline at week 24 in Physical Impacts and Cardiopulmonary Symptoms domain scores showed greater improvements with sotatercept vs placebo (both p<0.05).8
Additionally, sotatercept was associated with an 84 percent lower risk of a composite of death from any cause or nonfatal clinical worsening event vs placebo (hazard ratio, 0.16; 95 percent CI, 0.08–0.35; p<0.001).8
Our patient had an increase in Hb levels after sotatercept treatment, which was reported in 5.5 percent of sotatercept-treated patients in STELLAR. This AE was manageable with dose interruptions or reductions, and was not associated with treatment discontinuations.8
Post-hoc analysis on right heart function
A post-hoc analysis of STELLAR demonstrated improvements in RHC and echocardiographic parameters with sotatercept vs placebo, including PVR and mPAP, which may reflect partial remodelling of pulmonary arteries (ie, the proposed mechanism of action for sotatercept).9
In our patient, after three doses of sotatercept, 6MWD increased, and NT-proBNP returned to prehospitalization levels. As of March 2026, after eight doses of sotatercept, she remained alive without undergoing lung transplantation, with stabilized NT-proBNP level, better exercise tolerance and symptom control, as well as improvements in WHO FC (from III to II), LTOT (from 3 to 1 L/min), and 6MWD (+128 m). (Figures 1 and 2) Consistently, notable improvements in both echocardiography and RHC were demonstrated. (Table)
Sotatercept in CTD-PAH with ILD
Use of PAH-specific therapies has been a concern in patients with concomitant interstitial lung disease (ILD), as the majority of clinical trials failed or even demonstrated detrimental outcomes.10 In a recent study focusing on CTD-PAH patients with ILD, sotatercept demonstrated improvements in 6MWD, NT-proBNP, WHO FC, and supplemental oxygen requirements, with no evidence of adverse respiratory effects.11
Conclusion
Sotatercept has emerged as a promising treatment for PAH patients at intermediate–low, intermediate–high, and high risk.5 STELLAR and our case demonstrated improved exercise capacity in PAH patients treated with sotatercept, including those with CTD-PAH.8 Early discontinuation of the recent ZENITH and HYPERION trials due to strong efficacy further supports sotatercept’s role in PAH treatment.12,13
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This special report is supported by an education grant from the industry. 
