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.
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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)