SAT0097 DO COMORBIDITIES IMPACT PERSISTENCE OF FIRST TUMOR NECROSIS FACTOR INHIBITOR TREATMENT IN RHEUMATOID ARTHRITIS? DATA FROM TURKBIO

Background:Studies indicate that patients with rheumatoid arthritis (RA) are at increased risk of developing several comorbid disorders. Comorbidities affect treatment decisions, the effectiveness of the treatment, quality of life, RA prognosis, and survival rate [1].Objectives:The aim of thisstudyto investigate the impact of comorbidity on the first TNF inhibitor treatment persistence in RA.Methods:In the TURKBIO database, patients with an ICD 10-diagnosis of RA (M05 or M06) who started TNF inhibitor therapy between January 2011 and June 2019 were enrolled. Demographic and clinical characteristics, acute phase reactants, disease activity scores (DAS 28 CRP, HAQ, CDAI, VAS global), initial comorbidities and numbers, drug persistence, were evaluated. Kaplan-Meier plots and Cox proportional hazard regression analyses were performed.Results:A total of 1172 patients >18 years of age treated with TNF-α inhibitors were included in the study. The most prevalent comorbidities were: hypertension in 262 patients (32.6%), obesity in 254 (32.6%), osteoporosis in 178 (22.3%), chronic lung disease in 143 (17.9%) and depression in 126 (15.8%). The baseline characteristics are summarised in Table 1. The presence of comorbidity did not affect the survival rate of the first TNF inhibitor therapy in the RA patients (p: 0.65). Comorbidities had no effect on DAS28 CRP (> 1.2 reduction) responses at 6 and 12 months of treatment (p: 0.18, p: 0.83, respectively). As the mean disease duration increases, the persistence of the first TNF inhibitor decreases by 5%.Conclusion:This study demonstrated the increasing burden of comorbidities in RA. However, it suggested that the presence and number of comorbidities did not influence the rate of persistence in the first TNF inhibitor drug and the response to treatment.References:[1] Gabriel, S.E. and K. Michaud,Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases.Arthritis research & therapy, 2009.11(3): p. 229.Disclosure of Interests:None declared

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O26 Non-serious infections in patients with RA: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Rheumatology ◽

10.1093/rheumatology/keaa110.025 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Katie Bechman ◽

Kapil Halai ◽

Sam Norton ◽

Andrew P Cope ◽

Kimme L Hyrich ◽

...

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

British Society ◽

Tnf Inhibitor ◽

Drug Survival ◽

Increased Risk ◽

Serious Infections ◽

The Impact ◽

Biologics Register

Abstract Background Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number. Results There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1). Conclusion These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life. Disclosures K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.

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Rates of Serious Infections and Malignancies Among Patients with Rheumatoid Arthritis Receiving Either Tumor Necrosis Factor Inhibitor or Rituximab Therapy

The Journal of Rheumatology ◽

10.3899/jrheum.140853 ◽

2015 ◽

Vol 42 (3) ◽

pp. 372-378 ◽

Cited By ~ 41

Author(s):

Kalle Jyri Aaltonen ◽

Jaana Tuulikki Joensuu ◽

Liisa Virkki ◽

Tuulikki Sokka ◽

Pasi Aronen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Inhibitor ◽

Poisson Model ◽

Tnf Inhibitor ◽

Biologic Treatment ◽

Increased Risk ◽

Serious Infections ◽

Necrosis Factor

Objective.Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.Methods.The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.Results.In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63–2.3), 0.84 (95% CI 0.53–1.3), 0.98 (95% CI 0.60–1.6), and 1.1 (95% CI 0.59–1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.Conclusion.Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

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An increased risk of non-melanoma skin cancer during TNF-inhibitor treatment in psoriasis patients compared to rheumatoid arthritis patients probably relates to disease-related factors

Journal of the European Academy of Dermatology and Venereology ◽

10.1111/jdv.12675 ◽

2014 ◽

Vol 29 (4) ◽

pp. 752-760 ◽

Cited By ~ 32

Author(s):

P.P.M. van Lümig ◽

S.P. Menting ◽

J.M.P.A. van den Reek ◽

P.I. Spuls ◽

P.L.C.M. van Riel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Skin Cancer ◽

Tnf Inhibitor ◽

Related Factors ◽

Non Melanoma Skin Cancer ◽

Increased Risk ◽

Inhibitor Treatment ◽

Melanoma Skin

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SAT0084 SERUM ADIPOKINES PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH TNF-INHIBITORS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4458 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 976.2-976

Author(s):

M. Novella-Navarro ◽

B. Hernández-Breijo ◽

F. Genre ◽

L. Lera-Gómez ◽

V. Pulito-Cueto ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Remission Rate ◽

Binary Logistic Regression ◽

Negative Influence ◽

Normal Weight ◽

The Body ◽

Response To Treatment ◽

Bivariate Analysis ◽

Tnf Inhibitor ◽

Serum Leptin

Background:In recent years, the relationship between obesity and autoimmune diseases has taken interest, since adipose tissue has been identified as an endocrine organ that secretes cytokines (adipokines), among which leptin stands out as a soluble pro-inflammatory mediator associated with the body mass index (BMI).Objectives:The main objectives of this study are: i) to analyse the influence of BMI on clinical response in Rheumatoid Arthritis (RA) patients who initiate TNF-inhibitor (TNFi) therapy; ii) to analyse the differences in the serum profile of adipokines (leptin and adiponectin) according to BMI and their association with response to treatment.Methods:Observational study of a prospective cohort of 73 RA patients who initiated biological treatment with TNFi from the Complex Therapy Unit (CTU) of our Hospital. Patients were classified according to their BMI in normal-weight (BMI<25) and overweight/obesity (O/O) (IMC≥25). Demographic, clinical and laboratory variables were collected at baseline and at 6 months. Our outcome measures were DAS28-VSG remission (DAS28<2.6) at 6 months after TNFi initiation. Serum leptin and adiponectin levels were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA) at baseline and 6 months. A descriptive sample analysis comparing the characteristics of both patient subgroups was performed using Chi-square, T-test for independent samples and U-Mann Whitney. Likewise, a bivariate analysis was carried out by means of binary logistic regression to assess the probable association of the parameters studied with remission.Results:Of the 73 patients studied, 51% were classified in O/O group. The O/O patients presented higher levels of baseline CRP (16.69±6.16 vs 8.74±3.81, p=0.01). No statistically significant differences were observed in the remaining variables (sex, age at the beginning of the TNFi, disease duration, baseline DAS-28), as well as therapeutic variables (use of previous DMARDs and doses of methotrexate and/or steroids). Patients with overweight/obesity presented higher DAS28-ESR values at 6 months of treatment (3.59±1.14 vs 2.93±1.27, p=0.02) and achieved remission less frequently (18.9% vs 48.6%, p=0.007). Serum leptin levels were significantly higher in O/O patients, both baseline (29.39±21.50 vs 13.49±8.78, p<0.001) and 6 months (33.06±22.03 vs 14.77±9.50, p<0.001) after TNFi initiation. In addition, O/O patients were less likely to reach remission at 6 months than normal-weight patients. [OR= 4.04 IC95% (1.40-11.64); p=0.009]. Lower frequency of remission was associated to greater leptin levels at 6 months [OR=0.94 CI95% (0.90-098); p=0.012]. No differences in serum adiponectin were found between both subgroups of patients.Conclusion:In this RA patient cohort, overweight/obesity is associated with i) a reduced response to TNFi therapy and ii) a lower short-term remission rate. Within the adipokine profile, leptin seems to play a relevant role in the maintenance of pro-inflammatory activity with a negative influence on the response to TNFi therapy in O/O patients.References:[1] Versini M. et al. Autoimmun Rev. 2014; 13, 981-1000[2] Toussirot E et al. Life Sci. 2015;140: 29-36.Disclosure of Interests:Marta Novella-Navarro: None declared, Borja Hernández-Breijo: None declared, Fernanda Genre: None declared, Leticia Lera-Gómez: None declared, Verónica Pulito-Cueto: None declared, Laura Nuño: None declared, Alejandro Villalba: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Chamaida Plasencia: None declared

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POS0492 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER PREDICTS THE LIKELIHOOD OF EULAR NON-RESPONSE TO TNF INHIBITOR THERAPIES IN RA: RESULTS FROM A RETROSPECTIVE COHORT ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3396 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 478.2-479

Author(s):

L. Zhang ◽

C. van der Tog ◽

A. den Broeder ◽

T. Mellors ◽

E. Connolly-Strong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Value ◽

Molecular Signature ◽

Response Criteria ◽

Treat To Target ◽

Inadequate Response ◽

Tnf Inhibitor ◽

Target Setting ◽

The Impact

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

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TNF inhibitor therapy for rheumatoid arthritis

Biomedical Reports ◽

10.3892/br.2012.42 ◽

2012 ◽

Vol 1 (2) ◽

pp. 177-184 ◽

Cited By ~ 81

Author(s):

XIXI MA ◽

SHENGQIAN XU

Keyword(s):

Rheumatoid Arthritis ◽

Inhibitor Therapy ◽

Tnf Inhibitor

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Effectiveness of TNF inhibitor treatment with various methotrexate doses in patients with rheumatoid arthritis: results from clinical practice

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-207005 ◽

2014 ◽

Vol 74 (3) ◽

pp. e24-e24 ◽

Cited By ~ 7

Author(s):

Sofie H M Manders ◽

Wietske Kievit ◽

Eddy Adang ◽

Tim J Jansen ◽

Jan N Stolk ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Tnf Inhibitor ◽

Inhibitor Treatment

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Gene–environment interplay in the etiology of psychosis

Psychological Medicine ◽

10.1017/s003329171700383x ◽

2018 ◽

Vol 48 (12) ◽

pp. 1925-1936 ◽

Cited By ~ 26

Author(s):

Alyson Zwicker ◽

Eileen M. Denovan-Wright ◽

Rudolf Uher

Keyword(s):

Environmental Factors ◽

Genetic Risk ◽

Environmental Exposures ◽

Response To Treatment ◽

Human Potential ◽

Specific Gene ◽

Environment Interaction ◽

Gene Environment ◽

Increased Risk ◽

The Impact

AbstractSchizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene–environment interactions. Only a few specific gene–environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene–environment interaction is a common polymorphism in theAKT1gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

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Perceived clinical utility of a test for predicting inadequate response to TNF inhibitor therapies in rheumatoid arthritis: results from a decision impact study

Rheumatology International ◽

10.1007/s00296-020-04746-7 ◽

2020 ◽

Author(s):

Dimitrios A. Pappas ◽

Christine Brittle ◽

James E. Mossell ◽

Johanna B. Withers ◽

Jeraldine Lim-Harashima ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Decision Making ◽

Clinical Utility ◽

Tumor Necrosis Factor Inhibitor ◽

Medical Decision ◽

Inadequate Response ◽

Tnf Inhibitor ◽

Financial Outcomes ◽

Factor Inhibitor ◽

Therapeutic Decision Making

AbstractTumor necrosis factor inhibitor (TNFi) therapies are often the first biologic therapy used to treat rheumatoid arthritis (RA) patients. However, a substantial fraction of patients do not respond adequately to TNFi therapies. A test with the ability to predict response would inform therapeutic decision-making and improve clinical and financial outcomes. A 32-question decision-impact survey was conducted with 248 rheumatologists to gauge the perceived clinical utility of a novel test that predicts inadequate response to TNFi therapies in RA patients. Participants were informed about the predictive characteristics of the test and asked to indicate prescribing decisions based on four result scenarios. Overall, rheumatologists had a favorable view of the test: 80.2% agreed that it would improve medical decision-making, 92.3% said it would increase their confidence when making prescribing decisions, and 81.5% said it would be useful when considering TNFi therapies. Rheumatologists would be more likely to prescribe a TNFi therapy when the test reported that no signal of non-response was detected (79.8%) and less likely to prescribe a TNFi therapy when a signal of non-response was detected (11.3%–25.4%). Rheumatologists (84.7%) agreed that payers should provide coverage for such a test. This study shows that rheumatologists support the clinical need for a test to predict inadequate response to TNFi therapies. Test results were perceived to lead to changes in prescribing behaviors as results instill confidence in the ordering rheumatologist.

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