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EULAR 2017 | Daily Highlights
DRUG TROUGH LEVELS AND ANTIDRUG ANTIBODIES IN NONSELECTED ANKYLOSING SPONDYLITIS PATIENTS USING SELF-INJECTED ANTITNF DRUGSAbstract: OP0024
Authors: J. Hiltunen1, P. Parmanne1, T. Sokka-Isler2, T. Lamberg3, O. Kaipiainen-Seppänen4, P. Isomäki5, M. Kauppi6, L. Pirilä7, T. Uutela8, R. Tuompo1, H. Relas1, T. Yli-Kerttula9, H. Valleala1, M. Romu1, T. Rannio2, K. Paalanen2, A. Juha2, P. Ekman9, K. Tadesse1, J. Borodina2, P. Elfving4, R. Peltomaa1, M. Leirisalo-repo1, H. Kautiainen10, S. Jokiranta11, K. K. Eklund12,*
1Rheumatology, Helsinki University Hospital, Helsinki , 2Rheumatology, Central Finland Central Hospital, Jyväskylä, 3Immunobiology, United Medix Laboratories Ltd, Helsinki, 4Rheumatology, Kuopio University Hospital, Kuopio, 5Rheumatology, Tampere University Hospital, Tampere, 6Rheumatology, Päijät-Hämeen Central Hospital, Helsinki, 7Rheumatology, Turku University Hospital, Turku, 8Rheumatology, Central Hospital of Lapland, Rovaniemi, 9Rheumatology, Satakunta Central Hospital, Pori, 10Unit of Primary Health Care, Helsinki University Central Hospital, 11Research Programs Unit, Immunobiology, Helsinki University, 12Rheumatology, Helsinki University Central Hospital, Helsinki, Finland
Immunization to biological drugs can reduce the treatment efficacy and increase the risk of adverse events.
To determine the drug trough concentrations and anti-drug antibody (ADAb) levels of self-injected TNF-inhibitors, in non-selected patients with ankylosing spondylitis (AS) attending the rheumatological outpatient clinic, and to study the patient related factors affecting the immunization to antiTNF drugs.
A total of 313 patients with AS were recruited. A blood sample, taken 1-2 days prior to next drug injection, was obtained from 273 patients. Trough concentration of the anti-TNF drugs were measured with capture-ELISA (Promonitor EIA, Progenica), the levels of ADAb with radioimmunoassay (Sanquin Laboratories, The Netherlands), and the serum TNF-blocking capacity by using an in-house reporter gene assay. The clinical activity of AS was assessed using the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), and the Maastricht AS Entheses Score (MASES).
ADAbs were observed in 21 % of patients on adalimumab (n=99), in 0 % of those on etanercept (n=83), in 3 % of those on golimumab (n=79) and in 50% of those on certolizumab pegol (n=12). The BASDAI in ADAb positive patients was 1.4 (sd 1.4) and in the ADAb negative patients 2.0 (sd 1.8 p=0.060). Factors affecting the immunization to biological drug could be further analyzed in patients using adalimumab. Trough drug concentrations of adalimumab correlated with the presence of ADAb (r=-0.54, rp<e;0.0001). In adalimumab users higher BMI was associated with the presence ADAb (p=0.019, adjusted for gender, age, and the time of biological use). Of patients who used methotrexate (MTX) 12% were ADAb positive and of those who did not use MTX 28% were ADAb positive (p= 0.048 adjusted for gender, age, weight, and the time of biological use). The use of sulphasalazine was not associated with lower number of ADAb positive patients. Of adalimumab users with ADAb+ the mean BASDAI was 1.2 (sd 1.4) and of those without ADAb 1.9 (sd 1.9) (p=0.091). Of adalimumab users the drug concentration was in the target range (5-10 mg/l) in only 33% of patients.
The disease activity of AS patients using self injected antiTNF drugs was low. The immunization to adalimumab was relatively common in nonselected AS patient population. However, no clear association was observed between the presense of ADAb and the disease activity.
The study was financially supported by Pfizer
Disclosure of Interest:
J. Hiltunen: None declared, P. Parmanne: None declared, T. Sokka-Isler: None declared, T. Lamberg: None declared, O. Kaipiainen-Seppänen: None declared, P. Isomäki: None declared, M. Kauppi: None declared, L. Pirilä: None declared, T. Uutela: None declared, R. Tuompo: None declared, H. Relas: None declared, T. Yli-Kerttula: None declared, H. Valleala: None declared, M. Romu: None declared, T. Rannio: None declared, K. Paalanen: None declared, A. Juha: None declared, P. Ekman: None declared, K. Tadesse: None declared, J. Borodina: None declared, P. Elfving: None declared, R. Peltomaa: None declared, M. Leirisalo-repo: None declared, H. Kautiainen: None declared, S. Jokiranta: None declared, K. Eklund Grant/research support from: Pfizer has supported the study financially, Consultant for: Advisory board meetings BMS, MSD, Pfizer, Abbvie,, Speakers bureau: Lectures: BMS, Roche, Pfizer, Novartis
Differences in immunogenicity of available self-injected anti-TNF drugs might be used as selling arguments in the commercially competitive market. However, while associations between the appearance of anti-drug antibodies, its potential prevention with methotrexate-comedication and response to treatment have been shown in some studies, causality has not been proven. This seems particularly important in ankylosing spondylitis, where addition of methotrexate has not been shown to improve clinical response to anti-TNF agents, as recently confirmed in the SCQM cohort. In the latter study, only drug retention of infliximab was shown to be longer in the presence of methotrexate, provided that patients were non-smokers. The current abstract confirms that the appearance of anti-drug antibodies is lower in patients treated with etanercept and golimumab in comparison to adalimumab and certolizumab pegol. The proportion of patients with anti-adalimumab antibodies was lower in patients on methotrexate, but not sulfasalazine. However, the presence of anti-adalimumab antibodies was not associated with a higher disease activity, indicating that the use of anti-drug antibody assays is rarely useful in clinical practice, particularly as antibody detection is strongly influenced by the type of assay used (as presented in abstract OP0025)
PD Dr. Adrian Ciurea