Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
To evaluate the application of an acid dissociation procedure in monitoring patients with subtherapeutic serum concentrations of infliximab (IFX), adalimumab (ADL) and etanercept (ETN), using an immunoassay commercialized (Promonitor®-ETN, Progenika Biopharma, S.A., a Grifols Company).
Methods
For 3 years 612 trough samples were analyzed of 247 patients with different rheumatic pathologies treated with IFX (44 patients, 94 samples), ADL (123 patients, 289 samples) and ETN (80 patients, 229 samples). With the standard technology, ADA was detected in 27, 15 and 0% of the patients treated with IFX, ADL and ETN respectively, coinciding always with a level of undetectable drug.
92 samples quantified with detectable but subtherapeutic drug levels at the standard treatment (31 samples of 25 patients with IFX<2 mg/L, 38 samples of 26 patients with ADL<3 mg/L and 23 samples of 18 patients with ETN<2 mg/L), were analyzed for ADA after submitting them to an acid pre-treatment. The protocol of acidification consisted of the incubation of the serum during 15 minutes with acetic acid 300 mM and later neutralization with Tris 1 M fitting to a final dilution 1/10.
Results
With the protocol of acid dissociation anti-ADL antibodies were detected in 46% of the patients with subtherapeutic levels of ADL, which were undetectable with the standard assay (18 samples, 12 patients, middle age: 55 years, 67% women, diagnoses: 8 ankylosing spondylitis (BASDAI: 4,8±1,5), 3 rheumatoid arthritis and 1 psoriasic arthritis (DAS28: 3,5±0,2). In 7 cases ADA’s detection after acidificatión was produced already in the first request of monitoring at 6 months of initiated the treatment. In other 3 cases, ADA’s positive after dissociation confirmed a previous positive with the standard assay. Initially the treatment was kept with ADL in 5 patients, which ended up by turning out to be positives with the standard technology between 2 and 6 months after the positive with dissociation. Finally, in all the patients a change of treatment was necessary for lack of clinical response, being chosen by another anti-TNF before ADA’s evidence. ADL’s maximum concentration in the samples with a positive result was of 1,8 mg/L and the title of detected antibodies ranged between 35 and 282 UA/mL. Anti-IFX not anti-ETN antibodies were not detected after the acidificación of the samples by subtherapeutic concentrations of these two drugs.
Conclusion
1) The acid pre-treatment of the samples increases the sensibility of the test of detection of anti-drug antibodies breaking possible drug-antibody complexes.
2)The monitoring of immunogenicity in patients with subtherapeutic levels of ADL, following a protocol of acid dissociation, has allowed us to detect in a precocious way ADA’s presence in these patients contributing to the optimization of the treatment.
This study has received a grant from Spanish Society for Rheumatology.
Disclosure:
F. Llinares-Tello,
None;
J. Rosas,
None;
J. M. Senabre-Gallego,
None;
G. Santos-Soler,
None;
C. Santos-Ramirez,
None;
E. Salas-Heredia,
None;
X. Barber,
None;
J. Molina,
None;
C. Cano,
None;
A. Pons,
None;
G. Aire-MB,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/implementation-of-an-acid-dissociation-procedure-for-immunogenicity-detection-in-patients-treated-with-anti-tnf-drugs/