Intravenous anti–IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis - 05/02/15
, Ting Wen, PhD a, Allison Greenberg, BA a, b, Oral Alpan, MD c, Benjamin Enav, MD c, d, Ikuo Hirano, MD e, Kari Nadeau, MD, PhD f, Sergio Kaiser, PhD g, Thomas Peters, Dr rer nat g, Antonio Perez, MD, PhD g, Ieuan Jones, BA g, Jonathan P. Arm, MD g, Robert M. Strieter, MD, FCCP, MACP h, Ronald Sabo, BA h, Kulasiri A. Gunawardena, MD, MRCP i, ∗Abstract |
Background |
Eosinophilic esophagitis (EoE) is a chronic allergic disease with limited treatment options.
Objective |
We evaluated QAX576, an mAb against IL-13, in the treatment of patients with EoE.
Methods |
Patients (18-50 years) with proton pump inhibitor–resistant esophageal eosinophilia received intravenous QAX576 (6 mg/kg) or placebo (2:1) at weeks 0, 4, and 8 and were followed for 6 months. The primary end point was the responder rate for a greater than 75% decrease in peak eosinophil counts at week 12. Efficacy was to be declared if the lower 90% confidence limit for the proportion of responders on QAX576 was 35% or greater. Secondary end points included changes in esophageal eosinophil counts, symptoms assessed by questionnaire scores, and quantification of a series of biomarkers.
Results |
Twenty-three patients completed the study up to week 12, and 18 continued to the end of the study. For the proximal and distal esophageal biopsies combined, the responder rate was 12.5% (90% confidence limit, 1% to 43%) with placebo, compared to 40.0% (90% confidence limit, 22% to 61%) with QAX576. Although the primary end point was not met, the mean esophageal eosinophil count decreased by 60% with QAX576 versus an increase of 23% with placebo (P = .004), and the decrease was sustained up to 6 months. There was a trend for improved symptoms, particularly dysphagia. QAX576 improved expression of EoE-relevant esophageal transcripts, including eotaxin-3, periostin, and markers of mast cells and barrier function, for up to 6 months after treatment. QAX576 was well tolerated.
Conclusions |
QAX576 significantly improved intraepithelial esophageal eosinophil counts and dysregulated esophageal disease–related transcripts in adults with EoE in a sustained manner.
Le texte complet de cet article est disponible en PDF.Key words : QAX576, mAb, cytokine, TH2 cells, IL-13, eosinophilic esophagitis, randomized clinical trial, targeted therapy, mast cell, barrier function, transcriptome
Abbreviations used : CPA3, DSG1, EGD, EoE, hpf, MDQ, PRO, SAE
Plan
| Supported by Novartis Pharma AG (ClinicalTrials.gov Identifier: NCT01022970). |
|
| Disclosure of potential conflict of interest: M. E. Rothenberg has received consultancy fees from Immune Pharmaceuticals, Receptos, Pluristem Pharmaceuticals, Regeneron, and Novartis; has an equity interest in Immune Pharmaceuticals and Receptos and can receive royalty fees from Teva for reslizumab, which is under development; and is a coinventor on patent applications owned by Cincinnati Children's, concerning the eosinophilic esophagitis transcriptome. T. Wen is a coinventor of a patent application, owned by Cincinnati Children's Hospital, concerning the eosinophilic esophagitis transcriptome. B. Enav reports personal fees from QOL Medical outside the submitted work. I. Hirano reports personal fees from Novartis, Meritage, Aptalis, and Receptos outside the submitted work. S. Kaiser, T. Peters, I. Jones, J. P. Arm, and K. A. Gunawardena are employees of Novartis. R. Strieter is the Global Head for Translational Medicine for Respiratory disorders at Novartis Institutes of Biomedical Research and has stock equity in Novartis. R. Sabo and A. Perez are consultants for Novartis. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 2
P. 500-507 - février 2015 Retour au numéro
Article précédent
- Ramipril and metoprolol intake aggravate human and murine anaphylaxis: Evidence for direct mast cell priming
- Maria Nassiri, Magda Babina, Sabine Dölle, Günter Edenharter, Franziska Ruëff, Margitta Worm
- Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease
- John Croese, Paul Giacomin, Severine Navarro, Andrew Clouston, Leisa McCann, Annette Dougall, Ivana Ferreira, Atik Susianto, Peter O'Rourke, Mariko Howlett, James McCarthy, Christian Engwerda, Dianne Jones, Alex Loukas
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?