FRI0111 Analysis of real-life infliximab and adalimumab data: drug switching and fate of antidrug antibodies and trough levels over time. (12th June 2018)

• Record Type: Journal Article
• Authors: Ho, D.; Valtanen, S.; Havana, M.; Kröger, L.; Eklund, K.; Jokiranta, T.S.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 600
• Page End: 600
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.3052
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Infliximab (IFX) and adalimumab (ADL) are biological drugs used in the treatment of rheumatoid arthritis (RA), spondyloarthropathy (SpA), and juvenile idiopathic arthritis (JIA). Development of antidrug antibodies (ADAb) may lead to increased drug clearance and loss of therapeutic drug trough levels (TL). Switching to another drug may be necessary after ADAb development. Objectives: To use real-life data from a large Finnish rheumatology patient cohort to determine the association between drug switching and ADAbs and the fate of ADAbs and TLs after ADAb development. Methods: Serum samples for IFX or ADL ADAb and TL measurements from 1345 (567 RA, 479 SpA, and 299 JIA) rheumatology patients were taken on a clinical basis in daily practice in 20 Finnish referral hospitals. ADAb analyses were performed at Sanquin laboratories (Amsterdam, The Netherlands) using radioimmunoassays; TL analyses were performed at United Medix Laboratories (Helsinki, Finland) using commercial methods (Promonitor ELISA, Progenika Biopharma). Samples were collected and analysed from January 2012 until September 2017. ADAb values≥12 AU/ml were considered positive; ADAb values were classified as low (12–30 AU/ml), intermediate (30–100 AU/ml) and high (≥100 AU/ml). Results: On the basis of TL data, we identified 67 patients (5%) who switched drugs. Of these patients, 47 (70.2%) provided ADAb measurements for the first drug; 33 (49.3%) patients were ADAb positive. Most (22 patients, 63.6%) had high ADAbs. Forty-nine (73.1%) patients provided ADAb measurements for the second drug. Of these patients, 11 (16.4%) were ADAb positive against the second drug; seven (63.6%) had high ADAbs. We identified 48 (3.6%) ADAb-positive patients who provided at least one follow-up ADAb measurement. Of these patients, 32 (66.7%) experienced ADAb loss; most (24 patients, 50%) experienced complete ADAb loss (most recent ADAb value ≤12 AU/ml). Twenty-five patients that experienced ADAb loss had available TL measurements both before and after ADAb loss; 23 (92%) had increased TL after ADAb loss. Of the 16 patients that experienced ADAb gain, only 3/11 (27.3%) patients that had available TL measurements both before and after ADAb gain had increased TL after ADAb gain. Conclusions: ADAb positivity is associated with drug switching; ADAb development against a second biologic drug is common. A significant proportion of ADAb-positive patients lose ADAbs over time. ADAb loss is associated with TL increase. Disclosure of Interest: D. Ho Consultant for: Pfizer Oy, S. Valtanen: None declared, M. Havana: None declared, L. Kröger Consultant for: Roche, K. Eklund Grant/research support from: Pfizer, Speakers bureau: Abbvie, MSD, Pfizer, BMS, T. S. Jokiranta Grant/research support from: Pfizer, Consultant for: Abbvie, MSD, Pfizer, UCB