Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol
| Autor: | Gordana Kosutic, Anita Afzali, Alexandra Gutierrez, Marshall Spearman, Jason Coarse, Douglas C. Wolf, Scott D. Lee, Razvan Arsenescu, William J. Sandborn, Brian G. Feagan, Stefan Schreiber, Bincy Abraham, Gerry Parker |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Drug medicine.medical_specialty Time Factors media_common.quotation_subject Gastroenterology Persistence (computer science) 03 medical and health sciences 0302 clinical medicine Crohn Disease Internal medicine medicine Humans Immunology and Allergy Longitudinal Studies Certolizumab pegol Adverse effect media_common Crohn's disease biology business.industry Immunogenicity Antibodies Monoclonal Prognosis medicine.disease 030220 oncology & carcinogenesis Certolizumab Pegol biology.protein Female 030211 gastroenterology & hepatology Safety Antibody Calprotectin business Immunosuppressive Agents Follow-Up Studies medicine.drug |
| Zdroj: | Inflammatory Bowel Diseases. 23:1047-1056 |
| ISSN: | 1078-0998 |
| DOI: | 10.1097/mib.0000000000001100 |
| Popis: | BACKGROUND Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. METHODS PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. RESULTS Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. CONCLUSIONS This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524. |
| Databáze: | OpenAIRE |
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