Comparative Effectiveness of Sotatercept and Approved Add-On Pulmonary Arterial Hypertension Therapies: A Systematic Review and Network Meta-Analysis
Bibliographic record
Abstract
Abstract Background There are no direct comparisons of sotatercept to add-on therapies approved for pulmonary arterial hypertension (PAH). Objective This study aimed to compare the efficacy and safety of add-on sotatercept versus other add-on therapies using a network meta-analysis. Data Sources We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov until April 15, 2023, for randomized trials involving patients with PAH who were treated with add-on sotatercept or other add-on PAH therapies. Data Extraction Data extraction and risk-of-bias assessments were performed independently and in duplicate using the Cochrane RoB 2.0 tool. We performed a frequentist random-effects network meta-analysis using the restricted maximum-likelihood estimator and assessed the certainty of evidence using the GRADE (grading of recommendations assessment development, and evaluation) approach. Synthesis Our search found 18 trials (5,777 patients) eligible for analysis. Sotatercept reduces clinical worsening as compared with placebo (relative risk [RR], 0.21; 95% confidence interval [CI] = 0.11–0.41; with high certainty). Sotatercept probably reduces clinical worsening more, compared with add-on endothelin receptor antagonists (RR, 0.28; 95% CI = 0.14–0.55), inhaled prostanoid (RR, 40.21; 95% CI = 0.07–0.67), and prostanoid taken orally (RR, 0.32; 95% CI = 0.16–0.67; all with moderate certainty). Sotatercept probably improves 6-minute-walk distance compared with placebo (mean difference [MD], 36.89 m; 95% CI = 25.26–48.51). Although sotatercept probably improves 6-minute-walk distance more than add-on endothelin receptor antagonists (MD, 18.38 m; 95% CI = 5.92–30.84) and prostanoid taken orally (MD, 25.66 m; 95% CI = 13.71–37.61), it did not exceed the minimal clinically important difference of 33 m (both with moderate certainty). Conclusions Sotatercept is an effective add-on therapy for PAH, likely superior to many approved add-on PAH therapies in reducing clinical worsening.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.032 | 0.076 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.028 | 0.044 |
| Bibliometrics | 0.010 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".