Background/Purpose: Benepali, the etanercept biosimilar, is licenced in the UK for the same indications as the reference product, Enbrel.

In 2016, the Rheumatology Department at Blackpool Teaching Hospitals, after informing all the patients on Enbrel about Benepali, switched the patients that gave consent.

A proportion of these patients requested a switch back to Enbrel and therefore we aimed to investigate the reasons for Benepali withdrawal and if the loss of effect (LOE) is reflected in change of disease activity measures.

Methods: We included all the patients switched to Benepali from July 2016 to April 2018, identified from the departmental biologics database. Data were collected from patientsÕ records.

Baseline characteristics associated with Benepali withdrawal were explored by multivariate logistic regression analysis stratified by diagnosis (RA, SpA, PsA) and included age, gender, duration of disease, co- treatment with DMARDs, concomitant Methotrexate, number of biological DMARDs (bDMARDs) before Enbrel, duration on Enbrel, number of swollen and tender joints, baseline ESR and CRP; only for RA: seropositivity for RF and / or ACPA, DAS- 28 before any bDMARD, baseline DAS-28 and Patient Global Score (PGS); only for SpA: HLA- B27 status, BASDI before any bDMARD, baseline BASDI and pain Visual Analogue Score (VAS) and only for PsA: Baseline Patient (PtGA) and Physician Global Assessment (PGA).

Wilcoxon signed-rank test was performed to compare the various expressions of disease activity (DAS- 28 and PGS for RA, BASDI and pain VAS for SpA, PtGA and PGA for PsA, ESR, CRP) before switching to Benepali and before Benepali withdrawal in patients with LOE.

Results: A total of 72 patients on Enbrel were switched to Benepali, of which 19 (26,4%) switched back to Enbrel after 6 months [interquartile range (IQR) 3.5- 10] on the biosimilar product (Table). All the 19 patients had remained on Enbrel until the time of data analysis [follow- up period: 12 months (IQR 7.5- 15.5)].

The reasons of withdrawal were LOE (58%), adverse events (32%), infection (5%) and difficulty using the pen device (5%). In RA, the duration on Enbrel was associated with Benepali withdrawal [OR 1.43 (95% CI 1.02, 2.00)] and no statistically significant factors were found in SpA and PsA.

For RA, LOE is reflected in the DAS- 28 increase (2.99), PGS increase (40 mm), increase in tender joints (3.5) and CRP increase (2 mg/dl) (all p <0.05), whereas for SpA and PsA there was no statistically significant change in disease activity measures.

Conclusion: The majority (73,6%) had a good response to Benepali, which is in keeping with the current evidence. In RA, LOE is reflected only in the subjective measures, except for CRP. Interestingly, all the patients switching back to Enbrel, stayed on this treatment, which may indicate other contributing factors in withdrawal not identified by this study, due to the limitation of the small sample size.