SUMMARY

• Transitioning from bosentan to OPSUMIT was examined in several single-center and multicenter studies. Results demonstrated that transition to OPSUMIT was generally well tolerated.^1-8
• One prospective study evaluated the transition from ambrisentan to OPSUMIT in adult pulmonary arterial hypertension (PAH) patients resulting in clinical stability.⁹
• Retrospective studies demonstrated that the transition from endothelin reception antagonists (ERA), including bosentan and ambrisentan, to OPSUMIT resulted in clinical stability and was well tolerated.^6,10,11
• An additional retrospective study evaluating the transition from bosentan to OPSUMIT is available.¹²

CLINICAL DATA

Transitioning From Other ERAs to OPSUMIT

The timing of OPSUMIT administration subsequent to therapy with other ERAs is subject to the judgment of the treating physician, upon assessment of the benefit and risk to the patient from the timing of treatment interruption and continuation.

Transition From Bosentan to OPSUMIT

Aldalaan et al (2022)² conducted a prospective, open‐label, single‐arm, uncontrolled study (POTENT) to clinically assess patients with PAH, from the ongoing SAUDIPH registry, who switched from bosentan to OPSUMIT (N=50).

Results

• Mean age at diagnosis was 35±11 years and 39 (78%) patients were female; 52% and 48% of patients were in World Health Organization (WHO) functional class (FC) I/II and WHO FC III/IV, respectively.
• Mean 6-minute walk distance (6MWD) at baseline was 331.3±130.1 m.
• Forty-seven patients were on a combination therapy that included bosentan 250 mg, and 3 were on monotherapy with bosentan.
• After 1 year of switching from bosentan to OPSUMIT, 26% of patients shifted from WHO FC III/IV to WHO FC II/III; the probability of a patient being on WHO FC III/IV decreased from 0.41±0.09% to 0.11±0.04%, from baseline to month 12 (P=0.002).
• The estimated over time clinical and safety outcomes before and after switching from bosentan to OPSUMIT is summarized in the Table: Estimated Changes Over Time in Clinical Characteristics Before and After Switching From Bosentan to OPSUMIT.

• Gamma‐glutamyl transferase (GGT) levels decreased 11.8 U/L from baseline to month 12 (39.1±3.1 U/L; 95% CI, 32.9-45.3 vs 27.3±2.8 U/L; 95% CI, 21.7-32.9), with a significant negative mean change (-16.19±3.76 at month 12, P<0.001).
• The number of patients that showed events of clinical worsening after 3, 6, 9, and 12 months was 3, 9, 9, and 9, respectively.
  • These patients initiated other nonintravenous/subcutaneous (IV/SC) PAH therapy (n=8) and/or IV/SC prostanoids therapy (n=1) or experienced PAH related hospitalization (n=7); 4 of the patients that initiated treatment with other drugs were hospitalized.
• Cases of lung transplantation, atrial septostomy, or death were not registered.
• There was a 22% increase, from baseline to the fourth visit (month 12), in the number of patients meeting 3 low‐risk parameters (WHO FC, 6MWD, or N-terminal pro B-type natriuretic peptide [NT‐proBNP]; P=0.005).

Dawson et al (2018)³ conducted a single-center study of 92 patients who transitioned from bosentan to OPSUMIT (n=49) or ambrisentan (n=43).

Results

• The majority of patients were female (OPSUMIT, 73%; ambrisentan, 81%), and the most common etiology was connective tissue disease (CTD)-PAH.
• Most patients were WHO FC III at the time of transition, although a larger proportion of patients who transitioned to ambrisentan were WHO FC III/IV.
• The mean 6MWD was lower in the ambrisentan group. At the time of transition, right heart catheterization (RHC) and laboratory characteristics were generally similar in the 2 groups.
• The majority of patients with both pre and post transition data remained clinically stable. Clinically meaningful changes in 6MWD, defined as a ±40 m absolute change, were similar before and after transition for both OPSUMIT and ambrisentan.
• In the majority of patients with full pre and post transition RHC data, mean pulmonary arterial pressure (mPAP), cardiac index (CI), and right atrial pressure (RAP) improved or was unchanged following the transition.
• In patients with both pre and post transition data available, mean hemoglobin levels were comparable between groups both prior to and after the transition from bosentan. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were comparable prior to and following transitioning from bosentan to OPSUMIT.
• Mean (standard deviation [SD]) NT-proBNP levels before and after transition were 211 (383) vs 194 (538) pmol/L, respectively in OPSUMIT patients and 134 (208) and 116 (163) pmol/L, respectively, in ambrisentan patients.
• The median follow-up from date of transition to death or time of last review was 20.08 (interquartile range [IQR], 12.3725.98) months.
• The Kaplan-Meier estimates of survival at 1 and 2 years after transition for the overall population were 93.1% and 81.3%, respectively.
• The transition to a new ERA was well tolerated for most patients. Mild ankle edema was reported in 7 (14%) patients who transitioned to OPSUMIT and in 12 (28%) patients who transitioned to ambrisentan.
• Twelve other adverse events (AE) were reported by 7 (14%) patients who transitioned to OPSUMIT and 13 AEs by 10 (23%) patients who transitioned to ambrisentan. No AEs were associated with the transition protocol itself. Five patients died within 6 months of transitioning (OPSUMIT, n=3; ambrisentan, n=2). None of the deaths were considered related to ERA treatment.

Aypar et al (2018)⁴ conducted a single-center, 24-week prospective study that aimed to evaluate the clinical efficacy and safety of the switch from bosentan to OPSUMIT in 13 patients. An updated analysis including 27 patients over a period of 24 months was also conducted.⁸

Results: Initial Analysis

• The baseline characteristics of patients are presented in the Table: Selected Baseline Characteristics for Initial Analysis.

• The patients were monitored at baseline and at week 24.⁴
• OPSUMIT improved 6MWD from baseline (mean±SD, 466±35 m), at 12 weeks (mean±SD, 494±78 m; +28 m; P<0.05), and at 24 weeks (mean±SD, 507±58 m; +41 m; P<0.05).⁴
• There was no statistically significant difference in 6MWD between week 12 and week 24.
• Two patients had Down syndrome and could not perform the 6MWD test.⁴
• OPSUMIT did not significantly change resting oxygen saturation levels, oxygen saturation levels after 6MWD, brain natriuretic peptide (BNP), or systolic pulmonary arterial pressure at 12 weeks or at 24 weeks.⁴
• No patients experienced anemia, hepatotoxicity, peripheral edema, or any other AEs.⁴

Results: Updated Analysis

• The baseline characteristics of patients are presented in the Table: Selected Baseline Characteristics for Updated Analysis.

• OPSUMIT significantly improved 6MWD from baseline (mean±SD [range], 458±79 m [300-620]) at 6 months (mean±SD [range], 501±73 m [325-616] + 43 m; P<0.05), at 12 months (mean±SD [range], 514±82 m [330-626] + 56 m; P<0.05), and at 24 months (mean±SD [range], 532±85 m [330-682] + 74 m; P<0.05).⁸
• Although a statistically significant improvement in 6MWD during the first 6 months was observed, an incremental improvement after 6 months was not observed (P>0.05).⁸
• OPSUMIT did not significantly change WHO FC, oxygen saturation, and NT-proBNP levels (P>0.05).⁸
• None of the patients experienced anemia, hepatotoxicity, or peripheral edema.⁸

Saleemi et al (2018)⁷ conducted a retrospective single-center study that examined the transition from bosentan to OPSUMIT in 19 patients.

Results

• Bosentan was replaced with OPSUMIT as an instant switch after the last evening dose of bosentan, and follow-up was performed for ≥3 months after switching from bosentan to OPSUMIT.
• Baseline and follow-up data included FC assessment, proBNP levels, 6MWD, liver function tests (LFT), and hemoglobin levels.
• The mean (range) patient age was 38 (21-‍66) years, with 15 female patients and 4 male patients. Thirteen (68%) patients were diagnosed with idiopathic PAH (IPAH), 3 (16%) with congenital heart disease (CHD)-PAH, and 3 (16%) with CTD-PAH. The mean proBNP levels were 620 pg/mL before switch and 442 pg/mL after switch (P=0.027).
• Preswitch and postswitch 6MWD was 300 and 362 m (P=0.0016), respectively. Most patients were WHO FC II (n=11) at baseline and at followup (n=7).
• Hemoglobin levels increased from baseline to follow-up (P=0.027). Two patients experienced abnormal LFT levels (ALT >3 times) on bosentan, while 0 patients experienced abnormal LFT levels (ALT >3 times) on OPSUMIT.

Blok et al (2017)⁵ published results from a prospective, multicenter, observational cohort study of 40 adult patients with CHD-PAH who were on bosentan and were transitioned to OPSUMIT. The study was evaluated after 6 months.

Study Design

• The transition to OPSUMIT was performed with a 24-hour washout period following cessation of bosentan.

Results

• The mean±SD age of patients was 45±13 years, 40% were male, 40% had Down syndrome, and 75% had Eisenmenger syndrome.
• Before therapy transition, 52% and 48% of patients were in WHO FC II and WHO FC III, respectively.
• The mean±SD 6MWD was 394±125 m and most patients had normal renal function (median creatinine 80 μmol/L, IQR 81-93) and elevated NT-proBNP (median 723 ng/L, IQR 3111328).
• At 6 months after transition, the number of WHO FC III or IV patients significantly decreased, NT-proBNP levels significantly improved, and tricuspid annular plane systolic excursion (TAPSE) significantly improved, while hospitalization for heart failure, syncope, 6MWD, arterial oxygen saturation (SaO₂), and ferritin remained unchanged (Table: Clinical Outcomes Following Transition From Bosentan to OPSUMIT at 6 Months).
• The transition to OPSUMIT was well tolerated in this study cohort and no serious AEs were reported.
• After 6 months of treatment with OPSUMIT, a >1 mmol/L drop in hemoglobin was observed in 2 (5%) patients (-1.2 and -1.6 mmol/L respectively), without therapeutic consequences. LFTs remained stable (<3 × upper limit of normal [ULN]) for ALT and AST, except for 1 patient with a temporary ALT increase of >3 × ULN, which resolved spontaneously.
• One patient died due to sepsis 4 months after transition to OPSUMIT.

Safdar et al (2017)¹³ conducted a retrospective single-center study examining the transition from bosentan 125 mg twice daily (BID) to OPSUMIT once daily in 24 patients.^14,15

Study Design and Assessments

• Patients were advised to take their last evening dose of bosentan and then take the first dose of OPSUMIT the following morning, within 12 to 24 hours of the last bosentan dose.
• Assessments were collected before switch (baseline) and at 6 months after switch.

Efficacy Results

• At the time of treatment transition, the mean±SD patient age was 58±13 years, mean±SD duration of disease was 6.6±4.4 years, 21 patients were female (87%), 13 were Caucasian (54%), 6 were diagnosed with IPAH, and 10 (42%) and 14 (58%) patients were WHO FC II and III, respectively.
• Concomitant PAH drugs included sildenafil/tadalafil (n=8), sildenafil/tadalafil with inhaled treprostinil (n=5), IV treprostinil (n=1), sildenafil with epoprostenol (n=4), and inhaled treprostinil (n=1).
• The mean±SD duration of follow-up after the switch was 5.7±1.5 months, and all patients were alive at the time of follow-up.
• The preswitch and postswitch data were as follows:
  • The mean±SD 6MWD was 344±106 m and 319±85 m (P=0.181), respectively.
  • No significant changes were observed in oxygen saturation during the walk test, and the Borg dyspnea score remained unchanged after the switch (P=0.606 and P=0.243, respectively).
  • Mean±SD BNP was 91±170 pg/mL and 90±137 pg/mL (P=0.93), respectively.
  • AST/ALT levels remained unchanged.
  • WHO FC was unchanged after switch (P=0.64) except in 2 patients. One patient reported WHO FC II symptoms preswitch and WHO FC III postswitch and the second patient reported WHO FC III symptoms preswitch and WHO FC II symptoms postswitch.
• Four patients who had edema before switch did not have edema after switch, and 5 patients who did not present with edema before switch presented with edema after switch.
  • The presence of edema remained unchanged in the remaining 12 patients (50% had edema before switch and 55% had edema after switch, P=0.743).
• Hemodynamic data were obtained from an echocardiogram performed before switch (n=24) and after switch (n=16).
  • There was no significant change in right ventricular systolic pressure (RVSP), RAP, cardiac output (CO), CI, and presence of pericardial effusion.
• Seventeen patients receiving combination therapy with bosentan and a phosphodiesterase type-5 inhibitor (PDE-5i) were switched to OPSUMIT and continued on their PDE-5i.
  • The postswitch PDE-5i dose remained unchanged. Preswitch and postswitch mean±SD 6MWD, BNP, and CI were 346±65 m and 298±78 m (P=0.129), 70±71 and 61±58 pg/mL (P=0.739), and 2.74±0.82 and 2.76±0.85 L/min/m² (P=0.955), respectively.
  • There was no significant difference in these parameters when comparing data obtained from patients who were not taking a PDE-5i.

Safety Results

• None of the patients reported adverse effects such as hypotension, headache, or dizziness attributable to a PDE-5i after the switch.
• Two patients had to be switched back to bosentan because of intolerability.
• One patient with portopulmonary hypertension (PoPH) and hepatitis C had OPSUMIT stopped due to increased AST and ALT levels (>5×ULN).
• Another patient with scleroderma had OPSUMIT stopped because of tachyarrhythmia and malaise that developed after starting OPSUMIT. Symptoms ceased after the patient was switched back to bosentan.
• A third patient with PoPH and hepatocellular cancer underwent liver transplantation in July 2014 and was taken off OPSUMIT following the transplant.
• None of the switched patients required prostacyclin dose escalation or the addition of prostacyclin after the switch.

Gray et al (2015)¹ conducted a single-center study that examined the transition from bosentan 125 mg BID to OPSUMIT once daily in 25 patients.

Results

• Data were collected at baseline and after treatment transition. Two patients were excluded from the analysis, 1 due to trauma and the other due to the development of cancer.
• Nineteen WHO Group 1 (n=9 idiopathic; n=3 CHD; n=6 CTD; n=1 portopulmonary) and 4 WHO Group IV patients were enrolled.
• At baseline, the mean (SD) patient age was 55.6 (17.9) years, 16 (69%) were female, 18 (78%) were Caucasian, mean (SD) time from diagnosis was 61.1 (50.9) months, and 3 (13%), 13 (57%), and 7 (30%) patients were WHO FC I, II, and III, respectively.
• Concomitant PAH drugs at baseline included sildenafil (n=5, 22%), tadalafil (n=8, 35%), treprostinil IV/SC (n=5, 22%), epoprostenol (n=1, 4%), inhaled treprostinil (n=7, 30%), and selexipag (n=1, 4%).
• Transition from bosentan to OPSUMIT was well tolerated in 21 (91%) of the 23 patients.
• Of the patients available for pre and post transition assessments, no significant changes in LFTs (11 patients assessed), hemoglobin (20 patients assessed), BNP, or 6MWD (6 patients assessed) were observed.
• Seven patients in the study developed mild peripheral edema, 1 patient experienced worsening FC, and 2 patients discontinued treatment (1 due to worsening FC and the other due to worsening peripheral edema). No deaths were reported in the study.

Transition From Ambrisentan to OPSUMIT

Chen et al (2022)⁹ conducted a real-world, prospective, open-label cohort study to evaluate the safety, tolerability, and efficacy of transitioning from ambrisentan to OPSUMIT in patients with PAH using a rapid switch protocol.

Study Design

• The study consisted of a screening period followed by a transition phase (the first month), and then patients entered long-term follow up (12 months).
• All patients were transitioned from ambrisentan to OPSUMIT due to unsatisfactory treatment effect, a desire to obtain better treatment effects, or the desire to reduce financial burden.
• Patients needed to be stable for at least 3 months (defined as no worsening of WHO FC within 3 months, no clinical evidence of heart failure, and diuretic dose increase less frequently than once per month) and had used ambrisentan for at least 6 months before transition with a stable dose for at least 3 months. Patients also could not have WHO FC worse than FC III.
• Patients were instructed to take their last dose of ambrisentan at their regular time on the transition date and to take the new ERA (OPSUMIT) the next day.

Results

• Of the 145 patients who completed 12 months of follow up, most were female (74.5%) and WHO FC II (58.6%) at baseline. Patients had been receiving ambrisentan for a median of 1.5 years (IQR, 1.0-2.9) before the study.
• All 157 enrolled patients switched safely from ambrisentan to OPSUMIT within the first month of the study. There were 12 patients excluded from the analysis due to early discontinuation. Of the 12 patients that were excluded, 2 (1.3%) patients transitioned to a different manufacturer of ambrisentan, 3 (1.9%) patients transitioned back to ambrisentan due to psychological dependence, 4 (2.5%) female patients stopped OPSUMIT due to AEs, 2 (1.3%) patients required the additional of parenteral treprostinil due to disease progression, and 1 patient died at the 37-week follow-up. The death was not considered related to an ERA treatment.
• From baseline to month 12, WHO FC was unchanged in 93 (64.1%) patients and improved in 41 (28.3%) patients.
• The 6MWD improved from 424.74±82.34 m at baseline to 440.59±77.57 m at month 12 (P=0.004). There was also a decrease in NT-proBNP levels from baseline to month 12.
• Echocardiography found no significant differences in diameters of the right atrium, left atrium, left-ventricular end-diastolic dimension and pulmonary artery width. Decreases were seen in the basal diameter of the right ventricle and systolic pulmonary arterial pressure.
• Assessment by REVEAL 2.0 risk score showed a decrease in the proportion of patients considered high risk from baseline to month 12 and an increase in the proportion of patients considered intermediate or low risk.
• One or more AEs occurred in 107 patients (73.8%) throughout the study and most AEs began during the transition phase. The most frequent AEs included headache, peripheral edema, and anemia.
• The number of patients with anemia increased from 10 (6.9%) at baseline to a peak of 29 (20%) at month 6 and 22 (15.2%) at month 12.
• Of the 112 female patients, 13 (15.7% of the 83 in reproductive age) patients experienced menstrual disorders (most commonly menorrhagia and metrorrhagia). Four women experienced severe anemia after 2-4 months of transition that was attributed to the new therapy. OPSUMIT was discontinued and iron supplementation started for at least 3 months. No other patients discontinued OPSUMIT due to AEs.  

Transition From Bosentan or Ambrisentan to OPSUMIT

Several studies looked at the transition from bosentan and ambrisentan to OPSUMIT. These studies are briefly summarized in the Table: Summary of Retrospective Studies.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, Derwent^® (and/or other resources, including internal/external databases) was conducted on 27 March 2025.