S157 24-Month Sustained Clinical Response and Safety of RBX2660 in Participants With Recurrent Clostridioides difficile Infection: Subgroup Analysis
Notice bibliographique
Résumé
Introduction: Clostridioides difficile is an opportunistic pathogen that causes an estimated 500,000 infections per year in the United States. Microbiota-based treatments have shown promise in reducing recurrent Clostridioides difficile infection (rCDI), but long-term efficacy and safety data have been reported infrequently. Here, we present a subgroup analysis on the long-term efficacy and safety of RBX2660, a microbiota-based live biotherapeutic, in participants with rCDI in PUNCH CD Open-Label (NCT02589847), a prospective, multicenter, open-label phase 2 trial. Methods: PUNCH CD Open-Label participants enrolled between October 1, 2015, and March 6, 2017, were ≥18 years old with either ≥2 episodes of rCDI treated by standard-of-care antibiotic therapy after a primary CDI episode, or ≥2 episodes of severe CDI requiring hospitalization. All participants had a positive stool test for C. difficile or toxins within 60 days prior to enrollment and were on antibiotics to treat CDI at the time of enrollment. Participants received up to 2 doses of RBX2660 rectally administered 7 ± 2 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for CDI retreatment for 8 weeks after completing study treatment. In this post hoc subgroup analysis, we report the 6-, 12-, and 24-month outcomes of 8-week responders by age, sex, race, and number of prior CDI episodes. Results: Among the 142 participants treated with RBX2660 (evaluable population), 92% were white, 62% were female, 59% were ≥65 years of age, and 49% had >3 prior episodes of CDI. Sustained treatment response through 6-, 12-, and 24-months after treatment, respectively, was achieved by 98.0%, 97.9%, and 93.5% of participants < 65 years of age and by 96.8%, 93.1%, and 88.0% of participants ≥65 years of age (Figure). Similar sustained response rates were demonstrated in participants categorized by sex, race, and number of prior CDI episodes. As shown in Table, treatment-emergent adverse events (TEAEs) were reported by a similar percentage of participants across demographic subgroups between 6-12 months (range: 31% to 43%) and 12-24 months (range: 23% to 37%) after treatment with RBX2660, with most being gastrointestinal and mild to moderate in severity. Conclusion: Across demographic subgroups, the majority of RBX2660 responders showed a sustained clinical response, remaining free of CDI recurrence up to 24 months after treatment. Long-term safety data reinforce that RBX2660 is well-tolerated.Figure 1.: Sustained Clinical Response Across Demographic Subgroups Through 24 Months After RBX2660 Treatment Table 1. - Summary of Adverse Events Across Demographic Subgroups Through 24 Months After RBX2660 Treatment Adverse Events/Participants (%) Age Sex Race Number of Prior CDI Episodes < 65 Years ≥ 65 Years Female Male White Non-White ≤3 >3 Onset Interval N = 62 N = 87 N = 95 N = 54 N = 136 N = 13 N = 74 N =75 6-12 months 46/23 (37) 95/36 (41) 81/37 (39) 60/22 (41) 130/55 (40) 11/4 (31) 48/27 (36) 93/32 (43) 12-24 months 59/15 (24) 88/30 (34) 77/27 (28) 70/18 (33) 127/41 (30) 20/4 (31) 60/17 (23) 87/28 (37) Severity Mild 119/19 (30.6) 236/12 (13.8) 288/21 (22.1) 147/10 (18.5) 395/30 (22.1) 40/1 (7.7) 217/17 (23.0) 218/14 (18.7) Moderate 87/22 (35.5) 155/27 (31.0) 134/41 (43.2) 108/8 (14.8) 215/43 (31.6) 27/6 (46.2) 113/21 (28.4) 129/28 (37.3) Severe 36/9 (14.5) 92/34 (39.1) 50/19 (20.0) 78/24 (44.4) 110/40 (29.4) 18/3 (23.1) 59/19 (25.7) 69/24 (32.0)
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 | 0,004 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,011 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».