Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C
Notice bibliographique
Résumé
BACKGROUND: A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. However, it is not established which of the two licensed peginterferon products, peginterferon alpha-2a or peginterferon alpha-2b, is the most effective and has a better safety profile. OBJECTIVES: To systematically evaluate the benefits and harms of peginterferon alpha-2a versus peginterferon alpha-2b in head-to-head randomised clinical trials in patients with chronic hepatitis C. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until October 2013. We also searched conference abstracts, journals, and grey literature. SELECTION CRITERIA: We included randomised clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b given with or without co-intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi-randomised studies and observational studies as identified by the searches were also considered for assessment of harms. Our primary outcomes were all-cause mortality, liver-related morbidity, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. The secondary outcome was sustained virological response in the blood serum. DATA COLLECTION AND ANALYSIS: Two authors independently used a standardised data collection form. We meta-analysed data with both the fixed-effect and the random-effects models. For each outcome we calculated the relative risk (RR) with 95% confidence interval (CI) based on intention-to-treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risks of random errors (play of chance). Intervention effects on the outcomes were assessed according to GRADE. MAIN RESULTS: We included 17 randomised clinical trials which compared peginterferon alpha-2a plus ribavirin versus peginterferon alpha-2b plus ribavirin in 5847 patients. All trials had a high risk of bias. Very few trials reported data on very few patients for the patient-relevant outcomes all-cause mortality, liver-related morbidity, serious adverse events, and quality of life. Accordingly, we were unable to conduct meta-analyses on all-cause mortality, liver-related morbidity, and quality of life. Twelve trials reported on adverse events leading to discontinuation of treatment without clear evidence of a difference between the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI 0.57 to 1.22; I2 = 44%; low quality evidence). A trial sequential analysis showed that we could exclude a relative risk reduction of 20% or more on this outcome. Peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response in the blood serum compared with peginterferon alpha-2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I2= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype, and treatment history yielded similar results. Trial sequential analyses supported the results in patients with genotypes 1 and 4, but not in patients with genotypes 2 and 3. AUTHORS' CONCLUSIONS: There is lack of evidence on patient-important outcomes and paucity of evidence on adverse events. Moderate quality evidence suggests that peginterferon alpha-2a is associated with a higher sustained virological response in serum than with peginterferon alpha-2b. This finding may be affected by the high risk of bias of the included studies . The clinical consequences of peginterferon alpha-2a versus peginterferon alpha-2b are unknown, and we cannot translate an effect on sustained virological response into comparable clinical effects because sustained virological response is still an unvalidated surrogate outcome for patient-important outcomes. The lack of evidence on patient-important outcomes and the paucity of evidence on adverse events means that we are unable to draw any conclusions about the effects of one peginterferon over the other.
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 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 | 0,011 | 0,027 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,008 | 0,005 |
| Bibliométrie | 0,007 | 0,005 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,004 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,014 | 0,001 |
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 ».