Serum Trough Levels of Adalimumab Inversely Correlate with Disease Activity in Patients with Inflammatory Arthritis

Daman Langguth¹, Peter Wong², Alison Bowling³, Hanish Bagga⁴, Di Freeman⁴ and emma ford⁵, ¹Immunology, Sullivan Nicolaides Pathology, Brisbane, Australia, ²Mid-North Coast Arthritis Clinic and University of New South Wales Rural Clinical School, Coffs Harbour, Australia, ³School of health and human sciences, Southern Cross University, Coffs Harbour, Australia, ⁴Mid-North Coast Arthritis Clinic, Coffs Harbour, Australia, ⁵Mid North Coast Arthritis Clinic, Coffs Harboyr, Australia

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Activity score, adalimumab and inflammatory arthritis

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster II: Prognostic Factors, Imaging and Miscellaneous Reports

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Targeted blockade of TNF has been a major advance in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). However, many patients lose response to a TNF inhibitor. One possible mechanism for this is development of anti-drug antibodies (ADAb).

However, there is no standardised assay for detection of ADAb. It can be difficult to determine if ADAb have in vivo neutralising ability. Serum trough drug levels may be a more robust biomarker. We sough to determine if serum trough levels of adalimumab (ADL) correlated with disease activity in patients with RA, PsA and AS.

Methods:

This was a prospective observational cohort study in bDMARD-naïve patients aged 18-80 yo with RA, PsA and AS commencing ADL. Serum samples were collected 24 hours before a dose of ADL at baseline and months 4, 10 and 16. GRIFOLS Proteomika – Promonitor^TM ELISA assays were used to determine serum trough drug levels. These were correlated with the following measures: DAS28, SDAI, RAPID3, CRP, ESR for RA and PsA; and BASDAI, ASDAS, CRP, ESR for AS. Samples with a serum trough ADL level <0.01 μg /ml were assayed for ADAb.

Spearman correlation coefficients (rho values) and multiple regression analysis were used to assess relationship between variables. The significance threshold was set at p<0.05 (2-tailed).

Results:

There was a negative correlation between serum trough ADL levels and DAS28 (r=

-0.73, p=0.001) and SDAI (r= -0.50,p=0.05) in RA patients (n=7). Disease remission (DAS28<2.6) was associated with a serum trough ADL > 5 μg/ml. A negative correlation was found between serum trough ADL levels and BASDAI

(r= -0.52, p <0.001), ASDAS-ESR (r= -0.47, p <0.001) and ASDAS-CRP (r= -0.48, p <0.001) in patients with AS (n=22). A serum trough ADL level of 5-8 μg/ml was associated with lower ASDAS-ESR and ASDAS-CRP scores. Of the 32 blinded samples with a serum trough ADL <0.01 μg/ml, 26 were found to be baseline samples (ie, prior to ADL exposure). Of the remaining (non-baseline) samples, 5 had ADAb (mean±sem: 386± 158IU/ml) while 1 had no detectable ADAb (<10 IU/ml).

Conclusion:

There was a moderately strong negative correlation between serum trough ADL levels and markers of disease activity in RA (DAS28, SDAI) and AS (ASDAS-ESR, ASDAS-CRP, BASDAI). A serum trough ADL level of > 5 mcg/ml was associated with DAS28 remission in RA. A serum trough ADL level of 5-8 mcg/ml was associated with lower ASDAS-ESR and ASDAS-CRP scores. ADAb were present in almost all samples with undetectable serum trough ADL levels. Serum trough drug levels may be useful in dose titration of, or choice of bDMARD.

Disclosure: D. Langguth, Sullivan Nicolaides Pathology, 3,Roche Pharmaceuticals, 5,Novartis Pharmaceutical Corporation, 5; P. Wong, Novartis Pharmaceutical Corporation, 5,Roche Pharmaceuticals, 5,Abbott Immunology Pharmaceuticals, 5; A. Bowling, None; H. Bagga, Abbott Immunology Pharmaceuticals, 5; D. Freeman, None; E. ford, None.

To cite this abstract in AMA style:

Langguth D, Wong P, Bowling A, Bagga H, Freeman D, ford E. Serum Trough Levels of Adalimumab Inversely Correlate with Disease Activity in Patients with Inflammatory Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/serum-trough-levels-of-adalimumab-inversely-correlate-with-disease-activity-in-patients-with-inflammatory-arthritis/. Accessed .

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