P-616 Systematic review and meta-analysis of efficacy and safety of r-FSH biosimilars EMA-approved compared to reference r-FSH (follitropin alfa)
Notice bibliographique
Résumé
Abstract Study question Are recombinant FSH biosimilars approved by the European Medicines Agency (EMA) comparable in efficacy and safety to the originator follitropin alfa? Summary answer Pooled analysis from studies comparing EMA-approved biosimilars with the reference product did not detect differences in efficacy or safety between these two gonadotropins. What is known already A biosimilar is, according to EMA, a biological medicine highly similar to another already approved (‘reference’), and are approved according to the same standards of quality, safety and efficacy. Their development and approval opens a window of opportunity to make IVF treatments more affordable for the general population. Two previous meta-analysis of phase III non-inferiority randomized controlled trials (RCT) including non EMA-approved rFSH biosimilars (Chua et al., 2021 and Budani et a., 2021) have suggested that pregnancy and live births are lower with biosimilars compared to follitropin alfa. Study design, size, duration Systematic review with meta-analysis following PRISMA guidelines. Participants/materials, setting, methods Databases searched from inception to november 2021 were: PubMed-MEDLINE, WOS, The Cochrane Library, ClinicalTrials.gov, EudraCT and Google Scholar using these keywords: ‘biosimilars’, ‘follitropin alfa’, `originator’ and ‘ovarian stimulation’. RCTs and non-randomized comparative studies were included. Risk of bias was assessed with ROB-2 tool and Newcastle-Ottawa Scale studies. Pooled Odds Ratios (OR) and mean differences (MD) when applicable, with a 95% confidence interval (CI), were calculated. PROSPERO protocol registration has been requested. Main results and the role of chance After the systematic search,five studies were included in the meta-analysis: two phase-III RCT (Strawitzki, 2016 and Rettenbacher, 2015) and three non-randomized comparative studies, one of them prospective (Kaplan 2021) and the other two retrospective (Sprem Goldstajn, 2021 and Van den Haute, 2021) involving 2173 IVF cycles. Risk of bias was low for the two RCT and moderate for the observational studies. The OR of clinical pregnancy was 0.89 (95% CI = 0.74,1.07; I2=0%) and the OR of live birth was 0.86 (95% CI = 0.71,1.04; I2=0%). No differences were observed in the cumulative birth rate either (OR = 0.86; 95% CI = 0.68, 1.09; I2 0%). The total number of oocytes retrieved was similar (MD = 0.25; 95%CI,-0.93, 1.43; I2 79%); as it was the total dose of gonadotropins employed (MD=-19.56; 95% CI, -57.88, 18.76; I2 0%) and the length of the stimulation (MD = 0.12; 95% CI,-0.23, 0.47; I2 80%). The risk of Ovarian Hyperstimulation Syndrome was similar in both cases (OR = 1.36; 95% CI, 0.63, 2.91; I2 21%). Limitations, reasons for caution Main limitations of this meta-analysis include the fact that three of the five included studies are not randomized studies and two of them are retrospective, which can bias the results. Wider implications of the findings This is the first meta-analysis including only results from studies with biosimilars EMA-approved. The results show that there are no differences between the biosimilars and the reference in terms of efficacy or safety. Larger RCTs including patients with different patterns of ovarian response are needed to confirm these findings. Trial registration number Not applicable
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 tête enseignante, 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 ».