ReviewDrug design, development and therapy2026
Beyond Terminal Blockade: A Mechanism-Based Approach to Complement Inhibitor Selection in Paroxysmal Nocturnal Hemoglobinuria.
Review in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement inhibitor selection in paroxysmal nocturnal hemoglobinuria (PNH) can no longer be reduced to a binary class-level decision. Terminal C5 inhibitors provide durable control of intravascular hemolysis (IVH) and the most mature evidence for thromboembolic risk reduction, supporting their continued primacy in patients with high thrombotic risk or established venous thromboembolism. Persistent anemia during C5 inhibition is mechanistically heterogeneous. Before it is ascribed to extravascular hemolysis (EVH) or bone marrow failure (BMF), the adequacy of terminal complement inhibition should be confirmed, as incomplete IVH suppression may contribute to residual hemolysis in some patients. Among patients with confirmed terminal suppression, persistent anemia is driven primarily by C3-mediated EVH in a subset of patients, whereas in others it arises from underlying BMF or a combination of both. Differentiating among these mechanisms is a prerequisite for escalation decisions rather than an optional refinement. The proximal complement inhibitors pegcetacoplan (C3), iptacopan (Factor B), and danicopan (Factor D) address EVH-driven anemia but have not been evaluated in trials powered for thrombosis prevention, creating an asymmetry in the evidence base that demands explicit clinical reasoning. This review proposes a phenotype-driven longitudinal management strategy stratifying treatment decisions by dominant disease mechanism, thrombotic risk, and practical treatment context. Diagnostic approaches to differentiating EVH‑dominant, BMF‑dominant, and overlap phenotypes in the relevant patient subsets, comparative evidence across inhibitor classes, and mechanism-based escalation strategies are addressed in sequence, alongside high-risk clinical scenarios and an evidence-gap analysis to guide future research.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.