scholarly journals SAT0134 COMPARATIVE RISK OF CANCER ASSOCIATED WITH FIRST-LINE DMARDS USE IN RHEUMATOID ARTHRITIS: REAL WORLD EVIDENCE FROM THE OHDSI NETWORK

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1004.1-1004
Author(s):  
T. Duarte-Salles ◽  
M. Recalde ◽  
J. Weaver ◽  
E. Burn ◽  
K. Marinier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Risk ◽  
Full Time ◽  
First Line ◽  
Research Support ◽  
Site Specific ◽  
Hazard Ratios ◽  
Comparative Risk ◽  
Risk Of Cancer

Background:Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are recommended as first line treatment for rheumatoid arthritis (RA) patients, but limited information exists on the comparative risk of cancer associated with their use.Objectives:To compare the risk of incident overall (excluding non-melanoma skin) and site-specific cancers (colorectal, lung, lymphoma, leukaemia) associated with first-line use of csDMARDs in patients with RA.Methods:We conducted a multinational cohort study informed by data from 7 healthcare databases including claims and electronic medical records from 4 countries (SIDIAP-Spain, MDCR-US Optum-US, CCAE-US, IQVIA AMBEMR-US, IQVIA-Germany, THIN-UK) part of the Observational Health Data Sciences and Informatics (OHDSI) network. All patients aged ≥18 years who initiated methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), or leflunomide (LEF) as first-line monotherapy after a diagnosis of RA between 2005 to 2018 were eligible. Individuals with a prior diagnosis of another inflammatory arthropathy or cancer, or <1 year of follow-up were excluded. Patients were followed from 1-year after treatment initiation to the earliest of incident cancer, loss to follow-up, or 5-years. Cox proportional-hazard models for MTX against each other csDMARD were performed after propensity score stratification. A large set of negative control outcomes were analysed to calibrate hazard ratios (cHRs). Estimates were pooled where homogeneity across sources was adequate (I2<0.4).Results:Across the databases, 127,547 RA patients initiating csDMARD therapy were included in the analyses (MTX: 73,996, HCL: 36,381 SSZ: 9,383 LEF: 7,787). The pooled incidence rate of overall cancer for MTX was 22.8 per 1,000 person years. The pooled summary and source-specific estimated cHRs for overall cancer are shown below in Figure 1. While little difference was seen for HCQ and SSZ compared to MTX, LEF was consistently associated with a reduced cancer risk: pooled cHR (95% CI) 0.67 (0.59 to 0.76) and cHRs ranged from 0.53 (0.36 to 0.80) in CCAE-US to 0.84 (0.58 to 1.22) in SIDIAP-Spain. There were insufficient cases to look site-specific cancers within data sources, although pooled results suggest little risk difference in leukemia, lymphoma, colorectal, or lung cancers.Figure 1.Calibrated hazard ratios (cHRs) of overall cancer risk with their respective confidence intervals (95%CI) by study database. Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4.Conclusion:Compared to MTX users, patients treated with LEF had a lower risk of overall cancer. Risk of four specific cancers did not differ by first line csDMARD exposure.Disclosure of Interests: :Talita Duarte-Salles: None declared, Martina Recalde: None declared, James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Karine Marinier Employee of: Servier, Yesika Díaz: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

SAT0138 DRUG-RELATED PANCYTOPENIA AND LEUKOPENIA IN RHEUMATOID ARTHRITIS: ARE ALL CSDMARDS EQUAL?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1006-1007
Author(s):  
L. Carmona ◽  
J. Weaver ◽  
E. Burn ◽  
B. Illingens ◽  
D. Vizcaya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reference Group ◽  
Negative Control ◽  
Full Time ◽  
First Line ◽  
Research Support ◽  
Hazard Ratios ◽  
Comparative Risk ◽  
Treatment Analysis

Background:Cytopenia is a known side-effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). There is a lack of data on the comparative risk of cytopenia with different csDMARDs.Objectives:To assess the comparative risk of leukopenia and pancytopenia for the most frequently used first-line csDMARDs: methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), and leflunomide (LEF).Methods:The study used data from 7 databases from 4 countries: CCAE, MDCR, Optum, IQVIA Ambulatory EMR (US); IQVIA THIN IMRD EMR (UK); IQVIA Disease Analyzer EMR (Germany); and SIDIAP (Spain). Cohorts included adult patients with a diagnosis of RA from 2005 to 2019 with at least one-year prior follow-up, no prior inflammatory arthritis, initiaton of first-line csDMARD, and no cytopenia in the preceding 30 days. Participants were followed from one day after treatment initiation to the earliest of event occurrence, treatment discontinuation/switching plus 14 days in the on-treatment analysis, five years in the intent-to-treat (ITT) analysis, or loss to follow-up. MTX was used as reference group. Cox models were fitted with propensity score stratification for observed confounding and negative control outcomes calibration for residual error. Estimates across database were pooled where I2<40% was seen.Results:Overall 166,347 patients were included. Pooled rates of leukopenia and pancytopenia for MTX were 10.9 and 3.2 per 1,000 person years, respectively. Figure 1 and 2 show the results for the different databases and pooled estimates where applicable. Database estimates are not reported where adequate covariate balance not attained, and meta-analysis not shown where I2>0.4. MTX showed slightly higher hazards of leukopenia and of pancytopenia compared to LEF but no consistently differential risks compared to HCQ or SSZ.Figure 1.Calibrated hazard ratios (95% CI) vs MTX, on-treatment analysisConclusion:Cytopaenia is rare, and apparently more frequent with MTX and less with LEF. Since prior full blood counts were inconsistently obtained in fewer than 50% of csDMARD new users (e.g. more frequent in MTX [42%] than HCQ [32%] in CCAE and Optum; roughly equal in MDCR), these results should inform future monitoring recommendations.Figure 2.Calibrated hazard ratios (95% CI) vs MTX, ITT analysisDisclosure of Interests:Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Ruta Sawant Shareholder of: AbbVie, Employee of: AbbVie, Talita Duarte-Salles: None declared, Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

scholarly journals Association Between Intake of Fruits and Vegetables by Pesticide Residue Status and Total Cancer Risk

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 349-349
Author(s):  
Helena Sandoval-Insausti ◽  
Yu-Han Chiu ◽  
Dong Hoon Lee ◽  
Andres Ardisson Korat ◽  
Brenda Birmann ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Pesticide Residue ◽  
Pesticide Residues ◽  
Fruits And Vegetables ◽  
The United States ◽  
Health Study ◽  
Site Specific ◽  
Specific Cancer ◽  
Risk Of Cancer

Abstract Objectives Intake of conventionally grown fruits and vegetables (FVs) is a primary route of exposure to pesticide residues in the general population. While occupational exposure to pesticides used in agriculture is known to be carcinogenic, it is unclear whether exposure to residues of these pesticides through diet carries comparable risks. To address this question, we evaluated the relation of FV intake, classified according to their pesticide residue status, with risk of cancer. Methods This prospective cohort study included 150,830 women (Nurses’ Health Study, 1998–2012, and Nurses’ Health Study II, 1999–2013) and 29,486 men (Health Professionals Follow-up Study, 1998–2012) who had no history of cancer. FV intake was ascertained using validated food frequency questionnaires. We categorized FVs as having high- or low-pesticide-residues using a validated scoring system based on pesticide surveillance data from the US Department of Agriculture. We used multivariate-adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and site-specific cancer related to high- and low-pesticide-residue FV intake. Results A total of 18,969 incident cancer cases were documented during 1136,110 person-years of follow-up. In the pooled multivariable analysis, high-pesticide-residue FV intake was not significantly associated with cancer risk. The HR (95% CI) comparing individuals in increasing quintiles of high-residue FV intake to individuals in the lowest quintile were 0.99 (0.94, 1.04), 1.03 (0.98, 1.09), 0.98 (0.93, 1.04), and 1.00 (0.94, 1.06) (p, linear trend = 0.91). When specific sites were examined, we found no association between intake of high-pesticide-residue FVs and risk of any of the sites examined, including malignancies previously linked to occupational pesticide exposure. Similarly, intake of low-pesticide-residue FVs was unrelated to total or site-specific cancer risk. Conclusions These findings suggest that exposure to pesticide residues through intake of FVs at usual levels in the United States is not related to cancer risk despite well documented carcinogenesis in occupational settings. Funding Sources National Institutes of Health.

scholarly journals AB0229 A NATIONAL, MULTICENTER, SECONDARY DATA USE STUDY EVALUATING EFFICACY AND RETENTION OF FIRST-LINE BIOLOGIC TREATMENT WITH TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-LIFE SETTING FROM TURKBIO REGISTRY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1140-1141
Author(s):  
A. Yazici ◽  
Ö. Özdemir Işik ◽  
E. Dalkiliç ◽  
S. S. Koca ◽  
Y. Pehlivan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Real World ◽  
Retention Rate ◽  
Real Life ◽  
Retention Rates ◽  
First Line ◽  
Research Support ◽  
Biologic Treatment ◽  
Number Of Patients

Background:Tocilizumab (TCZ) is a human anti-interleukin (IL)-6 receptor antibody approved in Turkey for the treatment of rheumatoid arthritis (RA).Objectives:In this study our purpose was to describe the disease activity, quality of life (QoL), and retention rate in RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting.Methods:Anonymized patient registry of TURKBIO was used based in a national, multicenter, and retrospective context. We conducted a search in the registry between years 2013 and 2020 and included adult RA patients who were prescribed with TCZ as their first-line biologic treatment with a post-TCZ follow-up of at least 6 months. CDAI, DAS28-(ESR), and HAQ-DI scores in 6, 12, and 24 months were obtained. Pairwise comparison was carried out for survey scores across baseline and timepoints. Subgroup analysis for route of TCZ administration was performed. EULAR response criteria were used for response evaluation. Retention of TCZ was evaluated by Kaplan-Meier analysis.Results:Overall,130 patients with a mean RA duration of14 years were included in the study. 87.7% of the patients were female and mean age was53 (SD; 15.0). Median duration of follow-up was 18.5 months. Majority (90.8%) of patients were given tocilizumab via intravenous route at baseline. Number of patients with ongoing TCZ treatment and follow-up at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (<2.8) and DAS28-(ESR) (<2.6) scores were 61.5%, 44.6%, 30%, and 54.6%, 40.8%, 27.7%, respectively. CDAI, DAS28-(ESR) and HAQ-DI survey scores significantly improved at 6, 12 and 26 months, respectively (p<0.001) (Table 1) in both IV and SC TCZ subgroups. At 6, 12 and 24months 74.8%, 82.5% and 86.4% of patients achieved a EULAR good response respectively. Twenty-three patients (17.6%) discontinued TCZ at 24 months. Of these, 19 patients discontinued due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93%, 84.3%, and 72.2%, respectively (Figure 1).Conclusion:TCZ as a first-line biologic treatment was found to be clinically effective in this real-world study with a high retention rate. These results are in line with the results gathered from previous TCZ controlled and real-life studies in which TCZ was found clinically safe and effective.References:[1]Haraoui B, Casado G, Czirjak L, Taylor A, Dong L, Button P, Luder Y, Caporali R. Tocilizumab Patterns of Use, Effectiveness, and Safety in Patients with Rheumatoid Arthritis: Final Results from a Set of Multi-National Non-Interventional Studies. Rheumatol Ther. 2019 Jun;6(2):231-243.[2]Favalli EG, Raimondo MG, Becciolini A, Crotti C, Biggioggero M, Caporali R. The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives. Autoimmun Rev. 2017 Dec;16(12):1185-1195.[3]Haraoui B, Jamal S, Ahluwalia V, Fung D, Manchanda T, Khraishi M. Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Results from an Observational, Noninterventional Study. Rheumatol Ther. 2018 Dec; 5(2): 551–565.Disclosure of Interests:Ayten Yazici Speakers bureau: PFIZER, AbbVie, NOVARTIS, Özlem Özdemir Işik: None declared, Ediz Dalkiliç Speakers bureau: AbbVie, UCB Pharma, PFIZER, Roche, MSD, NOVARTIS, Süleyman Serdar Koca Speakers bureau: MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB Pharma, AMGEN, SANOFİ, Yavuz Pehlivan Speakers bureau: PFIZER, NOVARTIS, MSD, CELLTRION, Consultant of: PFIZER, Soner Şenel: None declared, Nevsun Inanc Speakers bureau: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Paid instructor for: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Consultant of: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Grant/research support from: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Servet Akar Speakers bureau: LILLY, MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, JANNSEN, UCB Pharma, AMGEN, Paid instructor for: LILLY, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB, AMGEN, Grant/research support from: PFIZER, Sema Yilmaz: None declared, Özgül Soysal Gündüz: None declared, Ayse Cefle Speakers bureau: UCB Pharma, PFIZER, MSD, AbbVie, AMGEN, NOVARTIS, Fatos Onen Speakers bureau: AbbVie, LILLY, MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, JANNSEN, UCB Pharma, AMGEN, İbrahim Etem-MENARINI, Paid instructor for: AbbVie, LILLY, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB Pharma, AMGEN, İbrahim Etem-MENARINI, Grant/research support from: PFIZER

THU0212 FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 331.1-331
Author(s):  
A. G. Sena ◽  
D. Granados ◽  
N. Hughes ◽  
W. Fakhouri ◽  
A. Hottgenroth ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Real World ◽  
Common Data Model ◽  
Full Time ◽  
First Line ◽  
Research Support ◽  
First Line Therapy ◽  
Line Therapy ◽  
Deutschland Gmbh ◽  
Full Time Employment

Background:Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

scholarly journals O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Assessment ◽  
Prevalence Rates ◽  
Clinical Predictors ◽  
Research Support ◽  
Related Data ◽  
Increased Risk ◽  
One Year

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (&gt; upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT &gt;1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

scholarly journals AB0330 HIGH REMISSION RATES IN RA – REAL LIFE DATA FROM BARITICINIB

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cox Regression ◽  
Real Life ◽  
Inadequate Response ◽  
Research Support ◽  
Das 28 ◽  
Patient Reported ◽  
One Year

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

scholarly journals SAT0032 INCIDENCE OF RHEUMATOID ARTHRITIS IN PATIENTS WITH NEW ONSET OF MUSCULOSKELETAL SYMPTOMS AND ANTI-CPP POSITIVITY COMPARED TO ANTI-CPP NEGATIVE PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 946.1-946
Author(s):  
S. Dauth ◽  
M. Köhm ◽  
T. Oberwahrenbrock ◽  
U. Henkemeier ◽  
T. Rossmanith ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Point Of Care ◽  
Early Arthritis ◽  
Clinical Parameters ◽  
Research Support ◽  
Point Of Care Test ◽  
Test Elisa ◽  
Patient Reported ◽  
New Onset

Background:Rheumatoid Arthritis (RA) is a chronic inflammatory joint disease. Strategies for its early detection and diagnosis are of high importance as prompt treatment improves clinical and structural outcome. Autoantibodies against cyclic citrullinated proteins (anti-CCP) have been associated with RA-development. Non-specific musculoskeletal (nsMSK) symptoms are often described prior to RA development. Majority of patients with nsMSK symptoms present to their general practice (GP) first. Studies of early arthritis cohorts have shown that many early arthritis patients cannot be accurately diagnosed at their first visit and are often referred as undifferentiated arthritis patients.Objectives:To evaluate the incidence of anti-CCP positivity in patients with new onset of nsMSK symptoms and the incidence of RA in these patients over a 3-year follow-up period compared to anti-CPP negative patients.Methods:In this prospective study (PANORA), 978 patients with new onset of nsMSK symptoms were included in 77 GP sites in Germany. Patients with a positive anti-CCP rapid-test (CCPoint®) were referred to Rheumatology Department (RD) for rheumatological assessment, RA-evaluation and an anti-CCP validation test (ELISA). ELISA anti-CCP positive patients without RA were monitored every 6 months for a total follow-up of 36 months or until RA-diagnosis. Patients with a negative anti-CPP result (CCPoint® or ELISA) are followed up with a questionnaire after 1 and 3 y.Results:From 978 included patients, 105 (10.7%) were CCPoint® positive. 96 were tested with ELISA and 27 (28.1%) were confirmed anti-CCP positive. 9 (33.3%) were diagnosed with RA at the first RD visit (study visit 2); 4 further patients were diagnosed with RA during the follow-up (FU) period so far. Overall, 48.1% of ELISA-positive (ELISA+) patients were diagnosed with RA up to now; 11 ELISA+ patients are still in the FU period of the study. Of the 868 CCPoint® negative patients, currently, 282 have filled out a 1-year FU questionnaire; 3.5% of those reported a RA diagnosis (Table 1). As expected, clinical parameters at V2 (e.g. CRP, swollen and tender joint count) were worse in the ELISA+/RA+ group compared to the ELISA-/RA- group, but no obvious differences were detected between ELISA+ patients who were diagnosed with RA during the FU period (after V2) and ELISA-/RA- patientsTable 1.Number and percentage of patients with a RA diagnosisAnti-CCP statusVisit 2Follow-up*TotalPoint-of-Care Test --3.5% (10 of 282)#3.5% (10 of 282)#Point-of-Care Test + / ELISA -2.9% (2 of 69)0% (0 of 34)#2.9% (2 of 69)Point-of-Care Test + / ELISA +33.3% (9 of 27)14.8% (4 of 27)48.1% (13 of 27)$* 1 year-questionnaire for Point-of-Care Test and ELISA negative patients or every 6 months follow-up for ELISA positive patients;#Patient-reported;$11 patients are still in the follow-up phase of the studyConclusion:Currently, 48.1% of anti-CCP+ (ELISA) patients have received a RA diagnosis, whereas 3.5% of the anti-CCP- (CCPoint®) received a RA diagnosis (patient reported), which underlines, that anti-CCP can be used as a marker to identify high-risk patients in GP setting. While clinical parameters are correlated with the diagnosis of RA, they are not suited for predicting future RA development alone. Anti-CCP, possibly in combination with additional parameters imaging, might increase the likelihood to early diagnose or predict RA development.Figure 1.Study overview: Patient distribution depending on anti-CCP results and RA diagnosis.Disclosure of Interests:Stephanie Dauth Grant/research support from: BMS, Michaela Köhm Grant/research support from: Pfizer, Janssen, BMS, LEO, Consultant of: BMS, Pfizer, Speakers bureau: Pfizer, BMS, Janssen, Novartis, Timm Oberwahrenbrock Grant/research support from: BMS, Ulf Henkemeier: None declared, Tanja Rossmanith Grant/research support from: Janssen, BMS, LEO, Pfizer, Karola Mergenthal Grant/research support from: BMS, Juliana J. Petersen Grant/research support from: BMS, Harald Burkhardt Grant/research support from: Pfizer, Roche, Abbvie, Consultant of: Sanofi, Pfizer, Roche, Abbvie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scripps, Janssen, and Novartis, Speakers bureau: Sanofi, Pfizer, Roche, Abbvie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scripps, Janssen, and Novartis, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai

scholarly journals FRI0046 PHARMACOGENOMICS-DRIVEN INDIVIDUALIZED PREDICTION OF TREATMENT RESPONSE TO METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A MACHINE LEARNING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 598.2-598
Author(s):  
E. Myasoedova ◽  
A. Athreya ◽  
C. S. Crowson ◽  
R. Weinshilboum ◽  
L. Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Machine Learning ◽  
Supervised Machine Learning ◽  
Research Support ◽  
Eular Response ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Early Ra ◽  
Genome Wide

Background:Methotrexate (MTX) is the most common anchor drug for rheumatoid arthritis (RA), but the risk of missing the opportunity for early effective treatment with alternative medications is substantial given the delayed onset of MTX action and 30-40% inadequate response rate. There is a compelling need to accurately predicting MTX response prior to treatment initiation, which allows for effectively identifying patients at RA onset who are likely to respond to MTX.Objectives:To test the ability of machine learning approaches with clinical and genomic biomarkers to predict MTX response with replications in independent samples.Methods:Age, sex, clinical, serological and genome-wide association study (GWAS) data on patients with early RA of European ancestry from 647 patients (336 recruited in United Kingdom [UK]; 307 recruited across Europe; 70% female; 72% rheumatoid factor [RF] positive; mean age 54 years; mean baseline Disease Activity Score with 28-joint count [DAS28] 5.65) of the PhArmacogenetics of Methotrexate in RA (PAMERA) consortium was used in this study. The genomics data comprised 160 genome-wide significant single nucleotide polymorphisms (SNPs) with p<1×10-5 associated with risk of RA and MTX metabolism. DAS28 score was available at baseline and 3-month follow-up visit. Response to MTX monotherapy at the dose of ≥15 mg/week was defined as good or moderate by the EULAR response criteria at 3 months’ follow up visit. Supervised machine-learning methods were trained with 5-repeats and 10-fold cross-validation using data from PAMERA’s 336 UK patients. Class imbalance (higher % of MTX responders) in training was accounted by using simulated minority oversampling technique. Prediction performance was validated in PAMERA’s 307 European patients (not used in training).Results:Age, sex, RF positivity and baseline DAS28 data predicted MTX response with 58% accuracy of UK and European patients (p = 0.7). However, supervised machine-learning methods that combined demographics, RF positivity, baseline DAS28 and genomic SNPs predicted EULAR response at 3 months with area under the receiver operating curve (AUC) of 0.83 (p = 0.051) in UK patients, and achieved prediction accuracies (fraction of correctly predicted outcomes) of 76.2% (p = 0.054) in the European patients, with sensitivity of 72% and specificity of 77%. The addition of genomic data improved the predictive accuracies of MTX response by 19% and achieved cross-site replication. Baseline DAS28 scores and following SNPs rs12446816, rs13385025, rs113798271, and rs2372536 were among the top predictors of MTX response.Conclusion:Pharmacogenomic biomarkers combined with DAS28 scores predicted MTX response in patients with early RA more reliably than using demographics and DAS28 scores alone. Using pharmacogenomics biomarkers for identification of MTX responders at early stages of RA may help to guide effective RA treatment choices, including timely escalation of RA therapies. Further studies on personalized prediction of response to MTX and other anti-rheumatic treatments are warranted to optimize control of RA disease and improve outcomes in patients with RA.Disclosure of Interests:Elena Myasoedova: None declared, Arjun Athreya: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Richard Weinshilboum Shareholder of: co-founder and stockholder in OneOme, Liewei Wang: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking

scholarly journals THU0207 SUSTAINABILITY OF RESPONSE TO UPADACITINIB AS MONOTHERAPY OR IN COMBINATION AMONG PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DMARDS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.1-328
Author(s):  
A. Kavanaugh ◽  
M. H. Buch ◽  
B. Combe ◽  
L. Bessette ◽  
I. H. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inadequate Response ◽  
Research Support ◽  
Two Phase ◽  
First Occurrence ◽  
Activity Measures ◽  
Disease Activity Measures

Background:The primary treatment goal for patients (pts) with rheumatoid arthritis (RA) is a state of sustained clinical remission (REM) or low disease activity (LDA).1,2Objectives:To assess the long-term sustainability of responses to upadacitinib (UPA), a JAK inhibitor, with or without background csDMARD(s) in pts with RA.Methods:Data are from two phase 3 randomized, controlled trials of UPA in RA pts with roughly similar baseline disease characteristics: SELECT-NEXT enrolled pts with an inadequate response (IR) to csDMARD(s) on background stable csDMARD(s) receiving UPA 15 mg or 30 mg once daily or placebo for 12 weeks (wks); SELECT-MONOTHERAPY enrolled methotrexate (MTX)-IR pts receiving UPA 15 mg or 30 mg monotherapy or blinded MTX for 14 wks. After 12/14 wks, pts could enter a blinded long-term extension and receive UPA 15 mg or 30 mg for up to 5 years. This post hoc analysis evaluated clinical REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI≤10; SDAI≤11), and DAS28(CRP) <2.6/≤3.2 at first occurrence before Wk 84; additionally, these measures were evaluated at 3, 6, and 12 months after the first occurrence for the total number of pts randomized to UPA 15 mg. Sustainability of response was evaluated by Kaplan-Meier only for those pts who achieved REM/LDA and was defined as time to the earliest date of losing response at two consecutive visits or discontinuation of study drug. The predictive ability of time to clinical REM/LDA was assessed using Harrell’s concordance (c)-index (for reference, an index ~ 0.5, indicates no ability to predict; an index of 1 or -1 would be a perfect prediction). The last follow up dates were 22 March, 2018 (SELECT-NEXT) and 25 May, 2019 (SELECT-MONOTHERAPY), when all pts had reached the Wk 84 visit.Results:Through Wk 84, the percent of treated pts achieving CDAI REM/LDA was 43%/79% for those receiving UPA 15 mg with background csDMARD(s) (SELECT-NEXT) and 37%/76% for those receiving UPA 15 mg without background csDMARD(s) (SELECT-MONOTHERAPY). 35%/25% of pts randomized to UPA 15 mg with background csDMARD(s) and 27%/23% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI REM through 6/12 months after the first occurrence. 64%/56% of pts randomized to UPA 15 mg with background csDMARD(s) and 61%/56% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI LDA through 6/12 months after the first occurrence (Figure 1). Time to initial clinical REM/LDA did not appear to be associated with sustained disease control. The c-indices (95%CI) for CDAI REM in the UPA 15 mg with background csDMARD(s) and UPA 15 mg without background csDMARD(s) groups were 0.541 (0.47, 0.62) and 0.568 (0.49, 0.65) and that of LDA were 0.521 (0.46, 0.58) and 0.498 (0.43, 0.56), respectively. Through last follow-up visit, 55% of pts receiving UPA 15 mg with background csDMARD(s) and 62% of pts receiving UPA 15 mg without background csDMARD(s) remained in CDAI REM while 72% and 70% of pts remained in CDAI LDA, respectively (Figure 2). Similar results were observed across other disease activity measures (SDAI REM/LDA and DAS28(CRP) <2.6/≤3.2).Conclusion:More than a quarter and more than a half of pts with RA and prior IR to csDMARD(s) receiving UPA with or without background csDMARD therapy achieved sustained clinical REM and LDA, respectively, across disease activity measures. Sustainability of responses appeared comparable among pts receiving UPA with or without background csDMARDs through up to 84 wks.References:[1]EULAR: Smolen JS, et al. Ann Rheum Dis 2017;76:960–977.[2]ACR: Singh et al. Arthritis & Rheumatology Vol. 68, No. 1, January 2016, pp 1–26.Disclosure of Interests: :Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

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