Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis
Machine Learning Data Imputation and Prediction of Foraging Group Size in a Kleptoparasitic Spider