Anti-Drug Antibodies to Certolizumab Pegol Are Assiciated with Low Drug Levels and Reduced Clinical Response at 3 Months in Patients with Inflammatory Joint Diseases

Johanna Gehin¹, Guro Løvik Goll², Silje Watterdal Syversen², David J Warren¹, Joseph Sexton³, Eldri Kvein Strand⁴, Tore Kvien⁵, Elisabeth Lie² and Nils Bolstad⁶, ¹Department of Medical Biochemistry, OUS-Radiumhospitalet, Oslo, Norway, ²Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ³Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ⁴Lillehammer Revmatismesykehus, Lillehammer, Norway, ⁵NOR-DMARD, EuroSpA Research Collaboration Network, Oslo, Norway, ⁶Department of Medical Biochemistry,, OUS-Radiumhospitalet, Oslo, Norway

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Antibodies, arthritis management, biologic drugs and certolizumab pegol

Session Information

Date: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Treatments Poster II: PROs, Safety and Comorbidity

Session Type: ACR Poster Session B

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

Background/Purpose:

Anti-drug antibodies (ADAb) to biological drugs predispose patients (pts) to low drug levels and lack of treatment response. For certolizumab pegol (CP) knowledge about the frequency and clinical relevance of ADAb is limited in pts with inflammatory joint diseases (IJD).

Objectives:
To assess the frequency and clinical relevance of early ADAb development in pts with inflammatory joint diseases treated with CP.

Methods: Pts from the NOR-DMARD study (n=310) with a clinical diagnosis of RA (91), PsA (61), axSpA (116) and other IJD (42) starting treatment with CP, who had available biobank sample at 3 months follow-up, were included. Serum samples are non-trough samples collected at 3 months. Drug concentrations were analysed using an in-house immunofluorometric assay automated on the AutoDELFIA immunoassay platform. ADAb was detected by a principal assay measuring neutralising ADAb and two confirmational tests (antigen-bridging test and a 3-step immunofluorometric assay).
Pts with RA, PsA and axSpA were included in response analyses. Treatment response was defined by EULAR good/moderate response in RA, DAS28 improvement ≥0.6 in PsA, and ASDAS clinically important improvement (CII) in axSpA.

Results:

After 3 months of treatment, 19 of 310 (6.1%) patients were ADAb positive (5 RA, 4 PsA, 6 axSpA and 4 other IJD). ADAb positive pts had significantly lower CP levels than ADAb negative pts, median 1.0 (IQR 0.2-6.8) vs 34.4 (IQR 21.2-44.7) mg/L (P<0.001).

Response data were available for 245 pts. Of these, only 1/11 (9%) ADAb-positive pts was classified as a responder, while 10/11 (91%) were non-responders. Among ADAb-negative pts with response data, 129/234 (55%) were responders, while 105/234 (45%) were non-responders.

Conclusion: ADAb against CP were detected in 6.1% of patients after 3 months of treatment and were associated with low drug levels and reduced treatment response. These results suggest that drug levels and ADAb may be important for the monitoring efficacy of treatment with TNF inhibitors, but the clinical significance needs to be examined in randomised clinical strategy trials.

Disclosure: J. Gehin, Roche, 5; G. L. Goll, AbbVie, Boeringer Ingelheim, Eli Lilly, Novartis, Pfizer, Orion Pharma, Roche, Sandoz, 5; S. W. Syversen, None; D. J. Warren, None; J. Sexton, None; E. Kvein Strand, Pfizer, Inc., 5; T. Kvien, AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, 5, 8,AbbVie, BMS, MSD, Pfizer, Roche, UCB., 2; E. Lie, None; N. Bolstad, Roche, 5,Orion Pharma, 5,Napp Pharma, 5,Pfizer, Inc., 5,Takeda, 5,Janssen, 5.

To cite this abstract in AMA style:

Gehin J, Goll GL, Syversen SW, Warren DJ, Sexton J, Kvein Strand E, Kvien T, Lie E, Bolstad N. Anti-Drug Antibodies to Certolizumab Pegol Are Assiciated with Low Drug Levels and Reduced Clinical Response at 3 Months in Patients with Inflammatory Joint Diseases [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-drug-antibodies-to-certolizumab-pegol-are-assiciated-with-low-drug-levels-and-reduced-clinical-response-at-3-months-in-patients-with-inflammatory-joint-diseases/. Accessed .

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