15 February 2020 by Vallerie V. McLaughlin

Selexipag dosing and titration in the first 500 patients enrolled in SPHERE (SelexiPag: tHe UsErs dRug rEgistry)

Introduction

SPHERE is an ongoing US-based, multicentre, prospective, registry collecting data on use of the oral selective IP prostacyclin receptor agonist selexipag in real-world settings. We report selexipag dosing and titration in the first 500 patients.

Methods

SPHERE (NCT03278002) will enroll 800patients newly initiated (≤60 days after starting selexipag) or previously initiated (>60 days after starting selexipag) at enrolment with a documented titration regimen. Patients are followed for up to 18 months. The highest dose is the maximum dose reached during up-titration within 6 months since initiation. Selexipag “maintenance dose” is the first dose received for ≥14 days without interruption or change;“titration speed” is the highest dose divided by time (weeks) to reach it.

Results

Data cut-off for this analysis, December 20, 2018. Demographics and disease characteristics are summarized (Table 1). Median maintenance dose of selexipag was 1200 µg BID (IQR: 800–1600 µg BID); median time to reach it was 8.1 weeks (IQR: 5.3–11.0 weeks). Low (≤400 µg BID), medium (600–1000 µg BID), and high (≥1200 µg BID) maintenance doses were attained by 15.1%, 30.8%, and 49.5% of patients, respectively (and in 23.2%, 31.2%, and 36.2%, respectively, in GRIPHON). Median titration speed was 175 µg BID/week (IQR: 110.5–195.3 µg BID/week), equating to 200 µg BID increase every 8 days, slightly slower than 200 µg BID every week (7 days) described in dosage and administration within FDA’s prescribing information.More patients discontinued due to adverse events in newly (29.0%) versus previously (14.1%) initiated groups, most commonly for worsening pulmonary hypertension (2.2%), headache (2.0%), myalgia (1.4%), and nausea (1.0%).

Conclusion

Median maintenance selexipag dose in SPHERE was 1200 µg BID, median titration speed was 175 µg BID/week; the vast majority of patients titrated slower than 200 µg BID/week. Safety profile was as observed in clinical trials.

Key Contributors

McLaughlin V1; Kim NH2; Hemnes AR3; Highland KB4; Chin KM5; Farber HW6; Zhao C7; Narayan V7; Shah M7; Chakinala MM8 1University of Michigan Medical Center, Ann Arbor, MI; 2University of California San Diego Medical Center, San Diego, CA; 3Vanderbilt University Medical Center, Nashville, TN; 4Cleveland Clinic, Cleveland, OH; 5University of Texas, Southwestern Medical Center, Dallas, TX; 6Tufts, Boston, MA; 7Actelion Pharmaceuticals US, Inc. South San Francisco, CA; 8Washington University School of Medicine, St. Louis, MO


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