Iloprost

證據等級: L5

預測適應症: 9 個

說明:此 Evidence Pack 含 9 個候選適應症,TxGNN 原始評分最高的 rank 1(頭皮單純性稀毛症)本身在 pack 的 mechanistic_link 中已被標註為「知識圖譜雜訊,缺乏生物學合理性」且為 L5/Hold。故本報告以證據等級最高、機轉最連貫的候選 —— PAH associated with HIV infection(rank 8, L1, S3, Proceed with Guardrails)—— 作為主要標的撰寫,而非機械套用陣列索引 0。

Iloprost: From Established PAH Treatment to HIV-Associated Pulmonary Arterial Hypertension

One-Sentence Summary

Iloprost is a prostacyclin (PGI2) analogue used as a class-standard treatment for WHO Group 1 pulmonary arterial hypertension (PAH), acting through pulmonary vasodilation and antiplatelet effects. The TxGNN model — together with supporting evidence in this pack — points to Pulmonary Arterial Hypertension Associated with HIV Infection as the most defensible repurposing candidate among nine TxGNN-predicted indications for this drug, supported by 1 completed Phase 3 RCT and 4 publications, including one systematic review.

Quick Overview

Item	Content
Original Indication	No confirmed original indication on file — this dataset lists 0 US marketing licenses for iloprost (market status: not marketed)
Predicted New Indication	Pulmonary Arterial Hypertension Associated with HIV Infection
TxGNN Prediction Score	99.21%
Evidence Level	L1
US Market Status	✗ Not Marketed
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not separately available in this dataset (top-level MOA field is empty), but the evidence pack’s own rationale text is consistent across multiple candidates: iloprost is a synthetic prostacyclin (PGI2) analogue that activates PGI2 receptors on pulmonary vascular smooth muscle, producing pulmonary vasodilation, inhibition of vascular remodeling, and antiplatelet aggregation. This is the core, well-established mechanism underlying iloprost’s use across the WHO Group 1 PAH disease family.

HIV-associated PAH is itself a recognized WHO Group 1 PAH subtype, sharing the same underlying pathophysiology (pulmonary endothelial dysfunction, vasoconstriction, and vascular remodeling) as idiopathic and familial PAH. The repurposing signal here is therefore not a mechanistically novel hypothesis but a sub-population extension of an already-established drug class effect — the same logic that applies to the other PAH-subtype candidates in this pack (congenital heart disease–PAH, connective tissue disease–PAH, hemolytic anemia–PAH, schistosomiasis-PAH).

It is worth noting that TxGNN’s raw highest-scoring predictions in this pack (hypotrichosis simplex of the scalp, congenital hypotrichosis milia) are explicitly flagged in the evidence pack’s own rationale as likely graph-topology noise with no plausible mechanistic link and zero supporting evidence (L5/Hold). Among the biologically coherent PAH-subtype predictions, the HIV-associated PAH candidate has the strongest evidence base (L1, one completed Phase 3 RCT), which is why it is prioritized here over the raw top-ranked candidate.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00709956	Phase 3	Completed	64	Multicenter, double-blind, randomized, placebo-controlled crossover study (PROWESS 15) assessing a single dose of inhaled iloprost on exercise capacity in symptomatic PAH patients — enrolled idiopathic/familial PAH and PAH associated with HIV or drugs/toxins, either treatment-naive or on stable background bosentan/ambrisentan/sildenafil

Note: this trial’s population includes HIV-associated PAH as one of several enrolled subgroups rather than an HIV-PAH-exclusive cohort; subgroup-specific efficacy data for the HIV-PAH population is not isolated in this pack.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
14720012	2003	Systematic Review	American Journal of Respiratory Medicine	Reviews prostanoid therapy across PAH etiologies, explicitly grouping HIV-associated PAH with idiopathic and collagen vascular disease–associated PAH as sharing near-identical obstructive pulmonary microvascular pathology
17195895	2006	Review	The Mount Sinai Journal of Medicine, New York	Overview of HIV-related pulmonary arterial hypertension, incidence (~0.5% of HIV-infected individuals), and treatment considerations
18260882	2007	Review	Kardiologiia	Reviews controlled trials of prostacyclin and synthetic analogues across PAH subtypes including HIV infection–associated PAH
31090367	2019	Registry/Cohort	Terapevticheskii Arkhiv	Six-year National Registry analysis of PAH prevalence, clinical course, therapy, and mortality

US Market Information

Currently no NDA or marketing authorization is on file for iloprost in this dataset — total_licenses is 0 and market status is recorded as “not marketed.” No product/dosage-form table can be produced from available data.

Safety Considerations

Please refer to the package insert for safety information. (All safety fields in this dataset — key warnings, contraindications, and drug interactions — are unpopulated; note that DG001 in the source metadata flags TFDA/FDA label warnings and contraindications as a Blocking data gap for safety pre-screening.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: HIV-associated PAH is a mechanistically coherent, class-established extension of iloprost’s core PAH indication, supported by a completed Phase 3 RCT and a systematic review — the strongest evidence tier (L1) among the nine candidates in this pack. However, the pivotal trial did not isolate HIV-PAH as a standalone efficacy cohort, and iloprost currently has zero marketing licenses on file in this dataset.

To proceed, the following is needed:

Resolve DG001 (Blocking): obtain TFDA/FDA package insert warnings and contraindications before any S1 safety pre-screening
Resolve DG002 (High): confirm detailed mechanism-of-action data directly from DrugBank rather than inferring from rationale text
Subgroup-level efficacy data for the HIV-PAH population specifically (from NCT00709956 or subsequent studies)
Drug-drug interaction review for concomitant antiretroviral therapy, given the target population
Formal regulatory filing pathway, since no existing NDA/marketing authorization exists for this product in the source dataset
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.