SAT0109 DISTINCT EFFECTS OF METHOTREXATE IN COMBINATION WITH ADALIMUMAB OR ETANERCEPT ACCORDING TO CCP ANTIBODY STATUS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: M. Greenwood, M. Shipa, M. Ehrenstein
Journal: Annals of the Rheumatic Diseases (2020)

Background: Considerable evidence suggesting enhanced efficacy of anti-TNF therapy for rheumatoid arthritis (RA) when co-administered with methotrexate (MTX) led us to explore the applicability of the published data to our patient cohort. Objectives: This retrospective study aimed to investigate the efficacy of MTX in combination with adalimumab (ADA) and etanercept (ETN) for RA, examining changes in disease activity score (DAS28-CRP) on first starting treatment, and rates of withdrawal due to inefficacy over up to 10 years of treatment in routine clinical practice. Methods: 309 patients with RA who had started ADA or ETN as a first-line biologic at UCLH from 2003 onwards were identified. Demographic and treatment details, DAS28-CRP (DAS) at the biologic-naïve baseline and at a first appointment for review on anti-TNF were extracted from clinical records. ANOVA was used to investigate the level of association between change in DAS and anti-TNF type, concomitant therapy, anti-CCP (CCP), rheumatoid factor (RF), age, disease duration and number of DMARD trials by anti-TNF initiation, year of initiation and gender. Kaplan-Meier with log rank tests were used to explore associations between anti-TNF type, MTX, CCP and RF and rates of withdrawal due to inefficacy, and Cox Proportional Hazards to check whether these remained significant after controlling for any other significant factors. Results: 179 patients were on ADA and 130 ETN; 44% were on concomitant MTX (Table 1). Table 1. Numbers of patients co-prescribed MTX with ADA or ETN according to CCP status CCP positive n Total n ETN without MTX 37 54 with MTX 57 76 ADA without MTX 54 82 with MTX 65 97 Median follow up since anti-TNF initiation was 7 years. Median age at initiation was 51 years, and disease duration 4 years. 82% were female. 241 were seropositive, including 24 positive for CCP only and 28 RF only. Mean biologic-naïve (baseline) DAS was 5.75, and 3.52 on first review (mean 20 weeks of treatment, n= 274) with mean change -2.23. MTX, even accounting for dose, failed to explain a significant amount of the variance in DAS response at first review either as a main effect or in interaction with anti-TNF type, CCP or RF. The only significant factor was 4+ DMARD trials prior to initiation (lower mean DAS response, p=0.010). Next, we analysed withdrawal of anti-TNF for inefficacy over up to 10 years. Kaplan-Meier analyses revealed that CCP positive patients had higher inefficacy withdrawal rates (p =0.004). Of note, CCP positive patients treated with MTX had lower withdrawal rates for inefficacy (Figure 1, p=0.006). Intriguingly, there was a trend towards higher rates in patients treated with MTX if CCP negative (p=0.14). Co-administration of MTX appeared to reduce rates of inefficacy withdrawal for patients on ETN (p=0.006) but not ADA (p =0.784). For CCP positive patients on ETN, MTX was strongly associated with lower rates of inefficacy withdrawal (Figure 1, p=.002). CCP status and the CCP*MTX interaction remained significant in the multivariate Cox model (Table 2). The MTX*ETN interaction was also included by the backward stepwise variable selection procedure although with p 0.069. Table 2. Variables in the Cox Model Hazard Ratio for discontinuation related to inefficacy 95% CI for HR MTX 2.18 0.93, 5.13 CCP 3.71 1.74, 7.92 CCP*MTX 0.35 0.14, 0.91 ETN*MTX 0.61 0.36, 1.04 Disease duration &gt; 5 years 0.61 0.41, 0.90 Gender (male) 0.62 0.36, 1.05 4+ DMARD trials 1.65 1.02, 2.67 Biologic-naive Global VAS/cm 1.26 1.11, 1.42 Overall model p &lt; .0005 RF with a univariate Cox significance of 0.172 was less closely associated with rate of withdrawal for inefficacy compared to anti-CCP positivity (p 0.005). Conclusion: There was no apparent benefit of MTX with anti-TNF with respect to initial DAS response, but MTX was associated with a reduction in withdrawals for inefficacy though only in CCP positive patients treated with ETN. Disclosure of Interests: None declared