Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response
Philippa D. K. CurryAndrew P. MorrisMeghna JaniHector ChinoyAnne BartonJames BluettJames BluettE G ChelliahC ChattopadhyayPauline HoAnne BartonMadhura CastelinoIan N BruceRachel GorodkinKimme L HyrichBen ParkerHector ChinoyTerri E. O’NeilAriane L. HerrickAnthony JonesRobert G. CooperWilliam G DixonBeverley HarrisonMeghna JaniAndrea LowEleanor KorendowychNeil McHughWilliam TillettNicola GoodsonSuzanne LaneL ShandIra PandeIan GaywoodFrances ReesMegan RutterS. HayatJ F McHaleA C JonesPeter LanyonAnil K. GuptaP A CourtneyA SrikanthAbhishek AbhishekStuart KyleRoope ManhasAnupama NandagudiS. Easter SelvanA. BharadwajNagui GendiRanda AlshakhSaima NazMohammad Kaleem AhmadLena DasM PattrickA P BowdenEric E. SmithP S KlimiukD J SpedenMarwan BukhariSvetlana KavaklievaL OttewellMarco MassarottiJon PackhamPippa WatsonPaul W. SandersS. HaqueBhupinder PalEllen BruceZ KarimK. MackayHolly A. ShielsJohn TaylorRachel JefferyP. K. NandiCharlotte FilerAbbas IsmailLouise MercerA. HassanAlistair B. RussellM DurraniW HassanA SamantaP SheldonJames N. FrancisAlison KinderR NeameArumugam MoorthyStefano BombardieriS. KellyJustin T. MaxwellMohamed AkilSimon TillLisa DunkleyRachel TattersallRachael KildingT TaitK-P KuetBarth D. GrantM KazmiD. GrahamV. E. AbernethyA. ClewesJulie DawsonG. FragoulisDevesh MewarE J TunnK NelsonTom D. KennedyClaire DuboisKaren DouglasEffie LadoyanniChristos KoutsianasNicola ErbRainer KlockeAndrew WhallettA PaceRavinder SandhuHolly JohnS A Young MinAnnie CooperJoanna LedinghamR G HullF McCraeWongShabanK PutchakayalaReena KumariGillian SmithChristopher MarguerieP ReynoldsCatherine A. ThorntonC GormanCaroline MurphyDaniel RoySarah HortonMadhura Castelino
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Abstract Objective The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Methods Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. Results In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Conclusion Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.Keywords:
Gee
Trough level
This study examined real-world etanercept and adalimumab treatment patterns in patients with psoriasis, psoriatic arthritis, or both.This retrospective analysis utilized data from patients with psoriasis, psoriatic arthritis, or both from a large, US claims database. Outcome measures included persistence on index therapy; pauses (7-59 days) and gaps (≥60 days) in therapy; and rates of discontinuing, switching and restarting index therapy in nonpersistent patients.Of 4,453 patients, 2,534 initiated etanercept and 1,919 initiated adalimumab. In psoriasis patients (n = 2,775), 46.4% and 56.8% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 49.0% and 56.3% discontinued, 23.8% and 22.4% restarted and 14.9% and 11.3% switched index therapy within 12 months. In psoriatic arthritis patients (n = 1,197), 60.7% and 63.3% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 48.3% and 51.6% discontinued, 25.8% and 20.0% restarted and 16.5% and 17.9% switched index therapy. In patients with both (n = 481), 58.1% and 59.6% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 42.7% and 63.2% discontinued, 24.3% and 12.6% restarted and 21.4% and 15.8% switched index therapy.Treatment modifications were common in patients with psoriasis, psoriatic arthritis, or both within 12 months of initiating etanercept or adalimumab.
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Results A total of 33 patients initially treated with Etanercept were switched to Adalimumab after a mean of 25.9 months (range 3–87 months). Reasons for discontinuation of Etanercept were inefficacy (n = 23, 65.8%), uveitis (n = 6, 17.1%), intolerance (n = 3, 8.6%) and patients' request (n = 6, 17.1%). Follow up data on Adalimumab were obtained from 12 patients for a range of 2 to 26 months (mean 10.9 months). The maximum response rate of the PedACR30/50/70 on Etanercept was 82.4%/73.5%/ 67.6%. The last documented response rate on Etanercept showed a decrease to 47.1%/35.3%/29.4% (PedACR30/ 50/70). After switching to Adalimumab a maximum PedACR30/50/70 of 75%/66.7%/50% compared to start of Etanercept and 33.3/33.3/25 compared to start of Adalimumab was reached. Treatment on both drugs was safe with no report of serious AE. Conclusion Although a number of patients have reached a good PedACR response rate on Etanercept, treatment was unsatisfied and therefore it was switched to Adalimumab. According to the PedACR only minor improvement was observed after switching to Adalimumab. from 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008
Discontinuation
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ObjectiveTo assess the clinical and economic efficiency as well as functional capacity in patients with rheumatoid artritis treated with biologic after dose reduction.
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Objectives: The objective of this study was to calculate adherence, persistence and 10-year switches in patients with PsA, by comparing adalimumab and etanercept in real life.Methods: The authors conducted a retrospective, observational, pharmacological and non-interventional study taking into consideration the dispensations of the study drugs at the Hospital Pharmacy, from 1 January 2007 to 31 December 2018. In the study, the authors considered adalimumab and etanercept. The authors calculated adherence to treatment through the relationship between received daily dose (RDD) and prescribed daily dose (PDD), and calculated persistence to treatment as the difference in days between the first and last dispensation.Results: The authors enrolled 113 patients, 60 treated with adalimumab and 53 with etanercept. Adherence levels were 0.83 for adalimumab and 0.84 for etanercept. Switches occurred in 42% of adalimumab and in 47% of etanercept prescriptions.Conclusion: In the treatment of PsA, persistence and switches are a problem for patients who cannot follow a consistent therapy over time, for clinicians who have to manage therapy suspension and changes, and for the National Health System that must procure and pay for a high number of drugs without information on their real value in terms of efficacy and safety of use.
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The aim of this study was to evaluate medication adherence and persistence of patients treated with Etanercept and Adalimumab for Rheumatoid Arthritis, also giving economic evaluations on therapy costs for Received Daily Dose (RDD).This retrospective study took into account 6 years from January 1, 2007 to December 31, 2012. Medication adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence has been reckoned taking into account the actual days of therapy comparing posology with supplied dose. The persistence has been graphed according to Kaplan-Meier method. The cost per RDD was reckoned starting from the expense incurred by Pescara General Hospital.Medication adherence gave results in values between 0.88-0.97 for Etanercept and 0.83-0.90 for Adalimumab. The value of persistence was 100% for Etanercept and 90% for Adalimumab for the first year, and 70% for Etanercept and 80% for Adalimumab for the second year. In the 3rd year the persistence for Etanercept was 50% while for Adalimumab it was 60%. In the fourth year the persistence for Etanercept was 21% while for Adalimumab it was 27%. The statistical analysis was conducted using the Log rank test. The average cost per RDD was €32.97 for Etanercept and for Adalimumab it was €32.00 as an average of 6 years.The medication adherence was good for both Etanercept and Adalimumab. The rate of persistence decreased strictly in the fourth year of treatment. This data suggests the need for continuous monitoring of patients in treatment with TNF blockers.
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Abstract Background: Etanercept and adalimumab are the most widely used biologic agents for psoriasis today. Large phase III trials have elucidated the much higher efficacy of adalimumab over etanercept; however, no head-to-head comparison data exist for these two medications. Objective: We report four cases of patients well controlled with Enbrel who flared when switched to adalimumab. In all four cases, the patient's psoriasis improved when switched back to etanercept. Conclusion: This brief report is intended to alert clinicians of the possibility that, despite the well-known average efficacy advantage of adalimumab over etanercept, some psoriasis patients experience better clinical outcome with etanercept than adalimumab. Therefore, despite the general efficacy difference between these two TNF inhibitors, it may be worth keeping in mind etanercept as an option in patients who have failed with adalimumab.Key words:: adalimumabEnbreletanerceptHumirapsoriasis Declaration of interest: Dr Bhutani has no financial conflicts of interest to report. Dr Koo has been a clinical researcher, consultant, and speaker for Abbott, Allergan, Amgen, Astellas, Galderma, Genentech, JSJ, Photomedex, Roche, Warner-Chilcott, and Teikoku.
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This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.
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