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Response to biologic drugs in patients with rheumatoid arthritis and antidrug antibodies
biologic disease–modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA).
OBJECTIVE To analyze the association of antidrug antibodies with response to treatment for RA.
DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed data from the ABI-RA (Anti-
Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk
of Immunization in Rheumatoid Arthritis Patients) multicentric, open, prospective study of patients
with RA from 27 recruiting centers in 4 European countries (France, Italy, the Netherlands, and the
UK). Eligible patients were 18 years or older, had RA diagnosis, and were initiating a new bDMARD.
Recruitment spanned from March 3, 2014, to June 21, 2016. The study was completed in June 2018,
and data were analyzed in June 2022.
EXPOSURES...Show moreIMPORTANCE There are conflicting data on the association of antidrug antibodies with response to
biologic disease–modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA).
OBJECTIVE To analyze the association of antidrug antibodies with response to treatment for RA.
DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed data from the ABI-RA (Anti-
Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk
of Immunization in Rheumatoid Arthritis Patients) multicentric, open, prospective study of patients
with RA from 27 recruiting centers in 4 European countries (France, Italy, the Netherlands, and the
UK). Eligible patients were 18 years or older, had RA diagnosis, and were initiating a new bDMARD.
Recruitment spanned from March 3, 2014, to June 21, 2016. The study was completed in June 2018,
and data were analyzed in June 2022.
EXPOSURES Patients were treated with a new bDMARD: adalimumab, infliximab (grouped as anti–
tumor necrosis factor [TNF] monoclonal antibodies [mAbs]), etanercept, tocilizumab, and rituximab
according to the choice of the treating physician.
MAIN OUTCOMES AND MEASURES The primary outcome was the association of antidrug antibody
positivity with EULAR (European Alliance of Associations for Rheumatology; formerly, European
League Against Rheumatism) response to treatment at month 12 assessed through univariate logistic
regression. The secondary end points were the EULAR response at month 6 and at visits from month
6 to months 15 to 18 using generalized estimating equation models. Detection of antidrug antibody
serum levels was performed at months 1, 3, 6, 12, and 15 to 18 using electrochemiluminescence (Meso
Scale Discovery) and drug concentration for anti-TNF mAbs, and etanercept in the serum was
measured using enzyme-linked immunosorbent assay.
RESULTS Of the 254 patients recruited, 230 (mean [SD] age, 54.3 [13.7] years; 177 females [77.0%])
were analyzed. At month 12, antidrug antibody positivity was 38.2% in patients who were treated
with anti-TNF mAbs, 6.1% with etanercept, 50.0% with rituximab, and 20.0% with tocilizumab.
There was an inverse association between antidrug antibody positivity (odds ratio [OR], 0.19; 95% CI,
0.09-0.38; P < .001) directed against all biologic drugs and EULAR response at month 12. Analyzing
all the visits starting at month 6 using generalized estimating equation models confirmed the inverse
association between antidrug antibody positivity and EULAR response (OR, 0.35; 95% CI, 0.18-0.65;
P < .001). A similar association was found for tocilizumab alone (OR, 0.18; 95% CI, 0.04-0.83;
P = .03). In the multivariable analysis, antidrug antibodies, body mass index, and rheumatoid factor
were independently inversely associated with response to treatment. There was a significantly higher drug concentration of anti-TNF mAbs in patients with antidrug antibody–negative vs antidrug
antibody–positive status (mean difference, −9.6 [95% CI, −12.4 to −6.9] mg/L; P < 001). Drug
concentrations of etanercept (mean difference, 0.70 [95% CI, 0.2-1.2] mg/L; P = .005) and
adalimumab (mean difference, 1.8 [95% CI, 0.4-3.2] mg/L; P = .01) were lower in nonresponders vs
responders. Methotrexate comedication at baseline was inversely associated with antidrug
antibodies (OR, 0.50; 95% CI, 0.25-1.00; P = .05).
CONCLUSIONS AND RELEVANCE Results of this prospective cohort study suggest an association
between antidrug antibodies and nonresponse to bDMARDs in patients with RA. Monitoring antidrug
antibodies could be considered in the treatment of these patients, particularly nonresponders to
biologic RA drugs.
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- All authors
- Bitoun, S.; Hässler, S.; Ternant, D.; Szely, N.; Gleizes, A.; Richez, C.; Soubrier, M.; Avouac, J.; Brocq, O.; Sellam, J.; Vries, N. de; Huizinga, T.W.J.; Jury, E.C.; Manson, J.J.; Mauri, C.; Matucci, A.; Abina, S.H.B.; Mulleman, D.; Pallardy, M.; Broët, P.; Mariette, X.; ABIRISK Consortium
- Date
- 2023-07-01
- Journal
- Jama Network Open
- Volume
- 6
- Issue
- 7