AB0345 THERAPEUTIC DRUG LEVELS TO ACHIEVE GOOD EULAR RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING ADALIMUMAB: RESULTS FROM THE BIOLOGICS IN RHEUMATOID ARTHRITIS GENETICS AND GENOMICS STUDY SYNDICATE (BRAGGSS) COHORT

Abstract

BackgroundRheumatoid arthritis (RA) is a systemic inflammatory disease often treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) such as Adalimumab (ADL), a tumour-necrosis factor inhibitor (TNFi). However, it is known that about a third of patients do not respond to ADL treatment. Previous studies have reported associations between poor response, decreased serum drug levels (SDLs) and poor adherence, but a therapeutic SDL has not been defined nor applied in clinical practice.ObjectivesTo assess median ADL SDLs in RA European Alliance of Associations for Rheumatology (EULAR) good vs non/moderate responders, and to determine cut-off SDLs associated with a “Good” response in fully adherent RA patients.MethodsIn a prospective observational cohort study, patients with RA were treated with ADL. At baseline, 3-, 6-, and 12-months patients had 4-component DAS28 scores, self-reported treatment adherence data and SDLs measured. Median drug levels and receiver-operator characteristics (ROC) curves were used to compare SDLs between responders and non-responders, and to establish cut-off SDLs in self-reported fully adherent patients. Serum drug levels were measured using a sandwich ELISA produced by Progenika Biopharma. Patients were considered fully adherent if they self-reported never having altered, forgotten or omitted any dose of their biologic drug at follow-up. Between group comparisons were assessed using Fisher’s exact test, with a threshold for significance set at p<0.05. Statistical analyses were performed in R Version 4.1.0 and RStudio Version 1.4.1106.ResultsA total of 283 RA patients taking ADL were included in the analysis. Baseline characteristics are shown in Table 1. Of these patients 93 (32.9%) self-reported being fully adherent to treatment at 3 months follow-up and had SDLs measured.Table 1.Baseline characteristics of patient cohort with RA taking ADL (n=283)CharacteristicnMissing (%)Age at baseline, median years (IQR)58 (51, 64)0Disease duration, median years (IQR)7 (3, 16)0Female Sex, n (%)206 (73)0BMI, median (IQR)27.4 (23.7, 31.9)0Smoking Status132 (46)Current, n (%)57 (38)-Ex, n (%)32 (21)-Non, n (%)62 (41)-On concurrent DMARD(s)1 (0.4)No, n (%)34 (12)-Yes, n (%)248 (88)-Baseline DAS Score, median (IQR)5.61 (5.18, 6.14)On MTX at baseline38 (13)No, n (%)44 (18)Yes, n (%)201 (82)In 93 fully adherent RA patients taking ADL at 3 months, good EULAR responders had significantly higher SDLs compared to non/moderate EULAR responders (p=0.0234). In 47/93 (50.5%) fully adherent good responders median SDL at 3 months was 10.94mg/L (IQR 7.75 to 12.0), whereas in 46/93 (49.5%) non/moderate responders, median SDL at 3 months was 9.014 (IQR 6.96 to 11.1).ROC analysis (see Figure 1) reported a 3-month non-trough ADL SDL cut-off of 7.5mg/L in fully adherent RA patients which discriminated Good EULAR responders compared to non/moderate responders with an AUC of 0.63 (95% CI 0.52 – 0.75), 39.1% specificity, and 80.9% sensitivity.Figure 1.ROC curve analysis: EULAR non/moderate vs good responders with 3 month ADL SDLs.ConclusionIn keeping with previous work, SDLs were higher in adherent compared with non-adherent patients, but this is the first study to demonstrate that SDLs are higher in fully adherent good EULAR responders compared with non/moderate responders. Based on our methods, cut-offs of 7.5mg/L for ADL may be useful targets in clinical practice to achieve good EULAR response.