POS0252 DIFFERENCES IN SERUM DRUG LEVELS AND ANTI-DRUG ANTIBODIES IN PATIENTS WITH INFLAMMATORY ARTHRITIS TREATED WITH ORIGINATOR VS BIOSIMILAR ADALIMUMAB

Abstract

BackgroundSerum drug levels and anti-drug antibodies (ADAb) impact the therapeutic effectiveness of most TNF-inhibitors. Possible differences in immunogenicity profile and pharmacokinetics across biosimilar and originator TNFi are still to be elucidated.ObjectivesTo compare serum drug levels, ADAb and treatment effect in patients treated with originator (Humira) vs biosimilar (Hyrimoz) adalimumab.MethodsPatients with a clinical diagnosis of spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) or other inflammatory arthritis (adult JIA or unspecified polyarthritis) enrolled in the observational NOR-DMARD study and starting treatment with adalimumab were included in the present analyses. Patients were started on originator adalimumab (Humira) up to January 2020 and biosimilar adalimumab (Hyrimoz) from January 2020, based on a national annual tender system for biological drugs in Norway. Serum drug levels and neutralising ADAb were measured using an in-house fluorescence method and compared between groups by Mann-Whitney U test and χ2-test respectively, in addition to multivariable regression analyses adjusted for age, sex, previous use of bDMARDs, smoking and co-medication with methotrexate. Treatment response at 3 months was defined by Major or Clinically Important improvement in SpA and EULAR good or moderate response in RA, PsA and other inflammatory arthritis, and, and compared by χ2-test. Drug survival the first two years of adalimumab treatment was explored by Kaplan-Meier curves and Cox proportional hazard regression analysis.ResultsA total of 378 patients (177 SpA, 98 RA, 70 PsA, 33 other) (median age 45.7 years [SD 14.2], 174 [46%]) female) were included. 240 (63%) patients started originator and 138 (37%) started biosimilar adalimumab. 139/378 (37%) patients used methotrexate as co-medication, the proportions and dosage were comparable for originator and biosimilar adalimumab. Patients on originator adalimumab had lower serum drug levels (6.5 mg/L [IQR 3.0-9.8] vs 8.3 mg/L [IQR 5.4-11.1], p=0.0003) (Figure 1A), and a higher rate of ADAb formation (33 [14%] vs 6 [4%], p= 0.004) compared to patients treated with biosimilar adalimumab. The differences in serum drug levels and ADAb were consistent in multivariable regression analyses (p= 0.032 and p= 0.020 respectively) and across diagnostic groups. There was no difference in treatment response or drug survival between originator and biosimilar adalimumab. (Table 1 and Figure 1B)ConclusionThis observational study showed higher occurrence of ADAb formation and lower adalimumab serum levels in patients on adalimumab originator vs biosimilar, indicating differences in the immunogenicity profile. There was, however, no significant difference in clinical outcomes.Table 1.Originator (Humira)(240)Biosimilar (Hyrimoz)(138)P-valueDiagnosis SpA113 (47%)64 (46%) RA59 (23%)39 (29%) PsA41 (17%)29 (21%) Other27 (13%)6 (4%)Co-medication methotrexate86 (36%)53 (38%)0.53#Previous use of bDMARDs90 (38%)39 (29%)0.048#Disease duration, median years (IQR)4.5 (IQR 1.2-13)4.8 (0.9-11.6)0.79*Responders at 3 months, no (%) SpA53/111 (48%)29/59 (49%)0.86# RA35/57 (61%)28/39 (72%)0.29# PsA25/41 (61%)22/28 (79%)0.12# Other17/27 (63%)4/5 (80%)0.46#*ranksum test#chi square testFigure 1.Serum adalimumab levels and drug survival, all diagnoses. A) Violin plot showing the probability density of the data at different values. Each data point is a participant, and the solid orange line show the group median.B) Drug survival the first two years of adalimumab treatment, stratified by originator (Humira) and biosimilar (Hyrimoz). P=0.14 (logrank test, not significant)REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Ingrid Jyssum: None declared, Johanna Elin Gehin: None declared, Eirik kristianslund: None declared, Joseph Sexton: None declared, David Worren: None declared, Yi Hu Speakers bureau: Boehringer, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Nils Bolstad: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB., Consultant of: Participation on advisory board.for AbbVie/Abbott, Galapagos, Pfizer, UCB.