The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study

PLOS ONE, Dec 2019

Objective To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. Methods This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6–24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. Results Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. Conclusion ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. Trial registration This study was registered on www.ClinicalTrials.gov (NCT01981473).

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175207&type=printable

The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study

April The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study Robert J. Moots 0 1 2 Ricardo M. Xavier 0 2 Chi Chiu Mok 0 2 Mahboob U. Rahman 0 2 Wen- Chan Tsai 0 2 Mustafa H. Al-Maini 0 2 Karel Pavelka 0 2 Ehab Mahgoub 0 2 Sameer Kotak 0 2 Joan Korth-Bradley 0 2 Ron Pedersen 0 2 Linda Mele 0 2 Qi Shen 0 2 Bonnie Vlahos 0 2 0 a Current address: Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ¤b Current address: Independent Consultant , Parsippany, New Jersey , United States of America 1 Aintree University Hospital, University of Liverpool , Liverpool , United Kingdom , 2 Hospital de Clinicas, Porto Alegre, Brazil, 3 Tuen Mun Hospital , Hong Kong , People's Republic of China , 4 Pfizer, Collegeville , Pennsylvania, United States of America, 5 Kaohsiung Medical University , Kaohsiung City, Taiwan , 6 Mafraq Hospital, Abu Dhabi, United Arab Emirates, 7 Institute of Rheumatology , Prague , Czech Republic 2 Editor: Michael Nurmohamed, VU University Medical Center , NETHERLANDS patient-reported outcomes. - Data Availability Statement: Data are available at https://clinicaltrials.gov/ct2/show/results/ NCT01981473. In addition to posting clinical trial results on the clinicaltrials.gov registry, Pfizer provides secure access to anonymized patient-level data to qualified researchers in response to scientifically valid research proposals. We confirm that interested and qualified researchers can Objective Methods To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6±24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays 2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. Results Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for request and obtain this data at the following link: http://www.pfizer.com/research/clinical_trials/trial_ data_and_results/data_requests. Funding: This study was sponsored and funded by Pfizer. The funder provided support in the form of salaries for authors [EM, SK, JKB, RP, LM, QS, BV], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the `author contributions' section. Competing interests: Dr. Moots has been a consultant for AbbVie, BMS, Celgene, Chugai, Hospira, MSD, Napp, Pfizer, Roche, and USB Pharma (the funds have supported the development of rheumatology care in East Africa). Dr. Xavier has been a consultant for AstraZeneca, Hospira, Janssen, and Pfizer, and on the speakers' bureau for AbbVie, AstraZeneca, Janssen, Pfizer, and Roche. Dr. Rahman is a former employee of and has stock in Pfizer. Dr. Tsai has been a consultant for AbbVie, Pfizer, and Roche. Dr. Pavelka has been a consultant for AbbVie, Amgen, BMS, Egis, MSD, Pfizer, Roche, and UCB, and on the speakers' bureau for AbbVie, Amgen, BMS, Egis, MSD, Pfizer, and Roche, UCB. Drs. Mahgoub, Kotak, Korth-Bradley, Pedersen, Mele, Shen, and Vlahos are all employees of Pfizer and own stock in Pfizer. Dr. Kotak was an employee of Pfizer at the time the work was done and owns stock in Pfizer. Drs. Mok and Al-Maini have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADLor IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. Conclusion ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. Trial regist (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175207&type=printable

Robert J. Moots, Ricardo M. Xavier, Chi Chiu Mok, Mahboob U. Rahman, Wen-Chan Tsai, Mustafa H. Al-Maini, Karel Pavelka, Ehab Mahgoub, Sameer Kotak, Joan Korth-Bradley, Ron Pedersen, Linda Mele, Qi Shen, Bonnie Vlahos. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study, PLOS ONE, 2017, Volume 12, Issue 4, DOI: 10.1371/journal.pone.0175207