Predicting therapeutic outcomes in Rheumatoid Arthritis using real-world pharmacogenetic and clinical data

Author(s):  
Fabian Hernandez ◽  
Luis Fernando Nino ◽  
Fabio Aristizabal
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 330-331
Author(s):  
S. Ciciriello ◽  
T. Smith ◽  
C. Osullivan ◽  
K. Tymms ◽  
P. Youssef ◽  
...  

Background:There are currently eleven biologic and targeted synthetic (b/ts)DMARDs acting via five different modes of action available for the treatment of RA in Australia. The cost of b/tsDMARDs is subsidized by government for patients that have active RA despite six months of combination csDMARD therapy. Once a patient is eligible, the clinician can prescribe the b/tsDMARD they deem to be the most clinically appropriate for the patient. In Oct 2015 the first JAK inhibitor (JAKi) became available in Australia (tofacitinib, TOF), baricitinib (BARI) became available in Sept 2018, and upadacitinib (UPA) in May 2020. Each of these oral tsDMARDs possess different selectivity profiles towards different members of the JAK family (JAK1–3 and Tyk2).Objectives:The aim of this analysis was to determine the patterns of JAKi cycling in real-world practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record during the routine consultation1. Data from patients >18 years with RA who commenced a b/tsDMARD between Jan-2007 and Dec-2020 were included in the analysis. A visual analytics software program was used to display data on medication initiation and cessation dates, and reasons for stopping tsDMARDs, which is recorded in the medical record at the time of the decision.Results:At Dec 2020, 28% of the 52,190 patients with RA in the OPAL dataset were prescribed b/tsDMARDs. Of these patients, 3,850 (26.3%) were currently prescribed a JAKi with 51.4% receiving TOF, 29.2% BARI and 19.4% UPA. In 2020, JAKi initiations accounted for 48.8% of all initiations and 30.7% of 1st line initiations; an increase of 6.1% and 3.5% from 2019, respectively. The percentage of patients switching from a first line JAKi to a second line JAKi rather than an agent with another mode of action increased from 33.1% in 2019 to 42.6% in 2020. This is despite 26.2% in 2019 and 45.8% in 2020 of the patients switching to another JAKi citing lack of efficacy as the reason for JAKi discontinuation. In the period between May 2020, when a third JAKi (UPA) become available, and Dec 2020, the majority of patients switching from first line TOF or BARI to another JAKI switched to UPA (69.4% and 83.9%, respectively), whilst 30.6% of first line TOF patients switched to BARI (30.6%), and 16.1% of first line BARI patients switched to TOF in second line. The majority of patients switching from second line TOF or BARI to a third line JAKi switched to UPA (73% and 96%, respectively), with 27% of second line TOF patients switching to BARI and a very low number moving from second line BARI to TOF (4%). JAKi choice after a third line TOF or BARI was almost exclusively UPA (86.2% and 95.5%, respectively).Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia and JAKi cycling is increasingly common in routine clinical care. Clinical outcomes and persistence following JAKi cycling requires further investigation.References:[1]Littlejohn GO, Tymms KE, Smith T, Griffiths HT. Using big data from real-world Australian rheumatology encounters to enhance clinical care and research. Clin Exp Rheumatol. Sep-Oct 2020;38(5):874-880.Figure 1.Patterns of JAKi cycling for the management of rheumatoid arthritis in first, second and third line switching.Acknowledgements: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 platformDisclosure of Interests:Sabina Ciciriello: None declared, Tegan Smith: None declared, Catherine OSullivan: None declared, Kathleen Tymms: None declared, Peter Youssef: None declared, David Mathers: None declared, Claire Deakin: None declared, Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Geoff Littlejohn Speakers bureau: 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.


Author(s):  
José-Luis Andréu ◽  
María Auxiliadora Martín ◽  
Héctor Corominas ◽  
José Javier Pérez-Venegas ◽  
José Andrés Román-Ivorra ◽  
...  

2021 ◽  
Vol 17 (4) ◽  
pp. 212-214
Author(s):  
José-Luis Andréu ◽  
María Auxiliadora Martín ◽  
Héctor Corominas ◽  
José Javier Pérez-Venegas ◽  
José Andrés Román-Ivorra ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 378-379
Author(s):  
B. Fautrel ◽  
R. Caporali ◽  
E. Holdsworth ◽  
B. Donaghy ◽  
M. Khalid ◽  
...  

Background:The principles of treat to target (T2T) include defining an appropriate treatment target, assessed at pre-defined intervals, with a commitment to changing therapeutic approach if the target is not met (1). T2T is recommended as a key strategy for the treatment of rheumatoid arthritis (RA).Objectives:To explore attitudes towards T2T, its implementation and stated treatment goals among physicians and their patients with RA.Methods:The Adelphi RA Disease Specific Programme™ was a large, quantitative, point-in-time survey conducted amongst rheumatologists (n=296) and their consulting patients with RA (n=3042) in Europe (France, Germany, Italy, Spain, UK) between Q4 2019–Q3 2020. Physicians were recruited via publicly available lists, completing an online survey and medical record extraction for their next 10–12 consecutive patients. The same patients were invited to voluntarily complete a self-report questionnaire (n=1098, 36% response), collecting data on attitudes towards T2T and treatment goals.Results:Physicians reported that 76% of patients were in remission (DAS28: <2.6) or had low disease activity (DAS28: 2.6 – 3.2), and 24% had moderate-high disease activity (DAS28: >3.2). Patient mean age was 53.0 years (SD 14.0), mean time since diagnosis was 7.2 years (SD 7.2). The proportion of patients currently receiving an advanced therapy (AT; defined as biologic or targeted synthetic DMARD) was 68%, of whom 70% were on a first line AT. No difference was observed between disease activity groups.In the physician survey, 86% of physicians stated they followed T2T principals in at least some of their RA patients, and would utilize a T2T approach in RA patients with moderate-high disease activity (61%), the most uncontrolled patients (37%) and those who do not respond well to initial therapy (34%). In this sample of real-world RA patients, 66% were reported by physicians to be on a T2T plan at the time of data collection. The most common physician-reported targets were remission (DAS28: <2.6) (75%), improvement of quality of life (QoL) (41%) and reduction of pain (31%), with 85% of physicians perceiving these treatment goals were fully or partially met. The most stated reasons for not implementing T2T was physician preference not to adjust current treatment (34%), patient preference not to adjust current treatment (23%), and there are no achievable goals for this patient (16%).Overall, 29% of patients reported they were involved in setting their T2T goals, while 34% stated their T2T goals were set by their physicians only, and 29% perceived no T2T goal had been set (n=620). The most common overall T2T goals from the patient perspective were remission (61%), controlling symptoms (41%), and reducing impact on QoL (34%). Of those patients who acknowledged a T2T goal had been set (n=407), 77% reported their T2T goal was fully or partially achieved.Of 719 patients who had moderate-high disease activity, 57% were on a T2T plan, with 46% of physicians perceiving these treatment goals were fully or partially met. The most common physician-stated reason for not implementing T2T was a lack of achievable targets (29%).Conclusion:Rheumatologists in this study reported a strong belief in T2T. The most common physician-set T2T goals were remission, improvement of QoL and reduction of pain, corresponding with T2T goals as reported by patients. However, a third of patients in this cohort were not aware of a defined T2T objective in their management, which may be a result of a perceived lack of achievable goals by physicians. It may be desirable to promote more patient involvement in defining achievable targets amongst those with moderate-high disease activity who despite best efforts may not reach a clinical state of remission. Further research is needed to identify and understand goals important to RA patients.References:[1]van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6.Acknowledgements:This study was funded by Galapagos NV, Belgium.Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), both funded by Galapagos NV.Disclosure of Interests:Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung Bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD, Elizabeth Holdsworth Employee of: Adelphi Real World, Bethany Donaghy Employee of: Adelphi Real World, Mona Khalid Shareholder of: Galapagos, Employee of: Galapagos, Mark Moore Shareholder of: Gilead Sciences, Speakers bureau: Gilead Sciences (only as employee), Paid instructor for: Gilead Sciences (only as employee), Consultant of: Gilead Sciences (only as employee), Grant/research support from: Gilead Sciences (only as employee), Employee of: Gilead Sciences, and previously Sanofi and AstraZeneca, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Yves Piette Consultant of: AbbVie, Amgen, Galapagos, Grünenthal and Sandoz, Grant/research support from: Amgen, Mylan and UCB, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, UCB, Janssen, Consultant of: AbbVie, Biogen, Fresenius, Galapagos, Gebro, Janssen, Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, Pfizer, Jasper Broen Shareholder of: Pharming Group, Consultant of: Galapagos, Gilead, Novartis, Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB, Grant/research support from: Celgene, Galapagos, Gilead, Lilly


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1872.1-1873
Author(s):  
S. H. Park ◽  
X. Han ◽  
F. Lobo ◽  
S. Nanji ◽  
D. Patel

Background:The shared epitope (SE) is a significant genetic risk factor for rheumatoid arthritis (RA), and it has been proposed to be associated with T-cell activation and the production of anti-citrullinated protein antibody (ACPA).1-3The results from the Early AMPLE trial, a head-to-head trial comparing the efficacy of abatacept versus adalimumab among early moderate-to-severe RA patients with positive ACPA (ACPA+) and rheumatoid factor (RF), showed that at week 24, patients with SE positivity (SE+) responded better to abatacept compared to adalimumab across all efficacy measures evaluated (ACR20 [American College of Rheumatology], ACR50, ACR70, DAS[disease activity score]28-CRP[C-reactive protein]).4Objectives:To compare the cost per responder (CPR) between abatacept and adalimumab among RA patients with SE+ at week 24 using the Early AMPLE trial data from a United States (US) payer perspective.Methods:A CPR analysis was conducted for RA patients with SE+, ACPA+, and RF. Responders were defined as patients achieving ACR20, ACR50, ACR70, or DAS28-CRP ≤2.6 and efficacy data was sourced from the trial (Figure 1).4Approved product labels were referenced for treatment dosing regimen and wholesale acquisition cost was used to calculate pharmacy cost.5A real-world rebate scenario was considered for adalimumab (30%) to reflect the real-world pricing in the US market. The CPR was calculated as the total pharmacy cost divided by the proportion of responders.Results:The total pharmacy cost at week 24 was $26,273 per patient for abatacept and $21,731 per patient for adalimumab. With achieving ACR70 as the definition of responder, the CPR at 24-week was $46,337 for abatacept and $74,935 for adalimumab, a difference of $28,598 (Table 1). The CPR was consistently lower for abatacept compared to adalimumab across all clinical measures, with difference ranging from $7,099 to $43,609.Table 1.Overall cost per responder resultsAbataceptAdalimumabDifferenceACR20$30,303.74$37,403.06-$7,099.32ACR50$34,254.68$48,077.83-$13,823.15ACR70$46,337.46$74,935.10-$28,597.64DAS28-CRP ≤2.6$52,546.68$96,155.65-$43,608.97Conclusion:While the pharmacy cost was higher for abatacept compared to adalimumab driven by the rebate, due to its higher clinical efficacy, the CPR was consistently lower for SE+ RA patients treated with abatacept. The results may be useful for US healthcare decision makers in understanding how to optimize treatment for SE+ RA patient while minimizing costs in today’s budget constrained environment.References:[1]Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.Arthritis and rheumatism. 1987;30(11):1205-13.[2]Holoshitz J. The rheumatoid arthritis HLA-DRB1 shared epitope.Curr Opin Rheumatol. 2010;22(3):293-8.[3]Sakkas LI, Bogdanos DP, Katsiari C, et al. Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment.Autoimmun Rev. 2014;13(11):1114-20.[4]Fleischmann R, Weinblatt M, Ahmad H, et al. Efficacy of abatacept and adalimumab in patientsn with early rheumatoid arthritis with multiple poor prognostic factors: post hoc analysis of a randomized controlled clinical trial (AMPLE).Rheumatol Ther. 2019;6(4): 559-571.[5]Truven Health Analytics. Redbook online. Accessed October 11, 2019.Disclosure of Interests:Sang Hee Park Consultant of: Pharmerit International, which received consultancy fees from Bristol-Myers Squibb (US), Inc. for this study, Xue Han Employee of: BMS, Francis Lobo Shareholder of: Bristol-Myers Squibb (US), Employee of: Bristol-Myers Squibb (US), Sakina Nanji Consultant of: Pharmerit International, which received consultancy fees from Bristol-Myers Squibb (US), Inc. for this study, Dipen Patel Consultant of: Pharmerit International, which received consultancy fees from Bristol-Myers Squibb (US), Inc. for this study


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1249.1-1250
Author(s):  
K. Celkys ◽  
J. Ly ◽  
M. Soden

Background:Biological and targeted synthetic disease modifying anti-rheumatic agents (bDMARDs) increase the risk of serious infections (SIs), however there is limited ‘real-world’ evidence comparing the relative risk of SI for individual bDMARDs. (1,2)Objectives:This study examines the rates of SIs in a non-select Australian Northern Queensland (NQ) cohort of patients with various rheumatic diseases receiving treatment with a bDMARD, to define predisposing factors and directly compare the bDMARDs.Methods:A retrospective review was performed for all patients who received a bDMARD through the Townsville Hospital Rheumatology Department over the 5-year period between June 2013 and May 2018. Episodes of a SI were defined as infection requiring admission or use of intravenous antibiotics. For each bDMARD the rate of SI per 100 patient years (PYs) was calculated and patient demographics and comorbidities were analysed. Between group differences were assessed using independent samples t-tests or ANOVA. Where assumptions were violated, Mann-Whitney U tests or Kruskal-Wallis tests were used. For categorical variables, chi-square tests were used, except when assumptions were violated when Fisher’s Exact tests were used.Results:296 patients received bDMARDs with an overall SI rate of 11.7/100PYs. There was no significant difference in presence of SI by disease type with 24% of patients with rheumatoid arthritis versus 19% with psoriatic arthritis, 14% with ankylosing spondylitis and 29% with “other” (X2=3.11; df=3; p=0.37). Respiratory tract infections were the most common infection (46%) followed by skin and soft tissue infections (23%). The highest incidence rate of SI occurred with rituximab (29.72 SI/100PYs) followed by certolizumab (22.50 SI/100PYs) and tocilizumab (15.00 SI/100PYs). Duration of time on a bDMARD, disease duration and use of methotrexate or leflunomide were not shown to significantly increase the risk of SI for the entire cohort. The characteristics which were shown to significantly increase SI rates were; prednisone use, increasing age, chronic pulmonary comorbidity and specifically in those with rheumatoid arthritis male gender and total duration of bDMARD use.Conclusion:In this real-world NQ cohort of patients treated with a bDMARD for a rheumatic disease, we have identified a number of factors potentially contributing to the risk of the development of SIs. This study provides valuable data on SI rates in an Australian ‘real-world’ cohort that may assist clinicians’ choice of bDMARD in patients with a high baseline risk of infection and highlights the importance of minimising prednisone use in patients on bDMARDs.References:[1]Ramiro S, Sepriano A, Chatzidionysiou K, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1093–1101.[2]Singh J, Wells G, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;16:CD008794.Disclosure of Interests: :Kate Celkys: None declared, Jason Ly: None declared, Muriel Soden Speakers bureau: Speaker Fees from Pfizer in 2016


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