The Safety and Efficacy of Ferumoxytol in the Treatment of Iron Deficiency: A Systematic Review and Meta-Analysis
Notice bibliographique
Résumé
Abstract Background Iron deficiency (ID) is one of the most common nutritional deficiencies worldwide, with an increased prevalence in pathological states such as end stage renal disease and inflammatory bowel disorders. Iron stores can be replenished by either oral or intravenous (IV) formulations, however IV formulations are known to raise iron stores more quickly and reliably. Ferumoxytol is an IV iron formulation used in the treatment of ID that, advantageously, can be given in large doses over a short period of time. Despite the initial large quantity of post-marketing reports of serious adverse events (SAEs), multiple clinical trials have failed to demonstrate a significant safety signal. Objectives To determine the safety and efficacy of ferumoxytol in the treatment of ID compared to other IV and oral iron formulations, and placebo. Methods This systematic review and meta-analysis was conducted following the Cochrane Handbook, and was reported as per Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles. All randomized or quasi-randomized controlled trials comparing ferumoxytol to alternate IV iron, oral iron, or placebo were included. Outcomes included treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), SAEs, related serious adverse events (RSAEs), hypotension or hypersensitivity reactions (HHR) and composite cardiovascular outcomes (CCO). Two review authors independently extracted data and assessed included studies for risk of bias. If required, additional data was sought from trial authors. Meta-analysis was performed using the Review Manager 5.3. Data was pooled using random-effects models. Risk of bias was assessed using the Cochrane Collaboration tool Risk of Bias. The GRADE approach was used to assess quality of evidence. Results The review included nine studies, one of which was a cross-over trial. These included 5691 participants (mean age 54.3, study mean range 30 to 65.1 years). Ferumoxytol was compared to alternate IV iron in three studies, to oral iron in two, and to placebo in four. Overall, studies were at low risk of bias (see figure 1). There was high quality evidence that relative to other IV iron formulations, ferumoxytol has little to no increase in the achievement of a minimum 1g/dL increase in hemoglobin (Relative Risk [RR] 1.04, 95%Confidence Interval [CI] 0.96 to 1.12; 767 participants pooled (pp) from 2 trials)), low quality evidence that it has little to no decrease in TEAE (RR 0.88, 95%CI 0.80 to 0.97; 2764 pp from 3 trials), little to no decrease in TRAEs (RR 0.73, 95%CI 0.61 to 0.88; 2764 pp from 3 trials), little to no increase on SAEs (RR 1.13, 95%CI 0.77 to 1.67; 2764 pp from 3 trials), and little to no decrease in RSAEs (RR 0.58, 95%CI 0.13 to 2.55; 2764 pp from 3 trials), very low quality evidence that it has little to no decrease in HHR (RR 0.58, 95%CI 0.31 to 1.09; 2764 pp from 3 trials) and moderate quality evidence that it has little to no decrease on CCO (RR 0.56, 95% CI 0.24 to 1.29; 2602 pp from 2 trials). Compared to oral iron, ferumoxytol had less TEAEs (RR 0.78, 95%CI 0.61 to 0.98; 515 pp from 2 trials), but compared to placebo ferumoxytol had more (RR 1.62, 95%CI 1.01 to 2.61; 2348 pp from 3 trials). Publication bias was not assessed due to the limited number of studies included. Conclusions Upon review of the available evidence, ferumoxytol is probably as efficacious as alternative IV iron formulations with no clear safety concerns. In addition, ferumoxytol had less TEAEs compared to oral iron formulations, but more compared to placebo. Disclosures Auerbach: AMAG Pharmaceuticals: Research Funding; Pharmacosmos A/S: Research Funding.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,013 | 0,029 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,001 |
| Méta-épidémiologie (sens large) | 0,021 | 0,035 |
| Bibliométrie | 0,007 | 0,007 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».