POS0636 INFLUENCE OF DEMOGRAPHIC AND DISEASE RELATED FACTORS ON EFFICACY OF INFLIXIMAB OR GOLIMUMAB IN RHEUMATOID ARTHRITIS. A META-ANALYSIS ON RANDOMIZED PLACEBO- CONTROLLED TRIALS

Background:TNF inhibitors have changed the course of rheumatoid arthritis (RA). Yet, detailed analysis on factors influencing clinical response to TNF inhibitors in RA is lacking.Objectives:Herein we aimed at studying the impact of demographics and disease-related factors on therapeutic response to golimumab and infliximab in RA.Methods:Randomized clinical trials (RCTs) that evaluated golimumab and infliximab versus placebo or conventional therapy were sought. We selected the following factors: age, sex, ethnicity, body mass index (BMI), smoking status, physical activity, disease duration, disease activity at baseline, presence of auto-antibodies. We studied the impact of these factors on clinical response using firstly aggregate data in a Mantel-Haenszel random effects model, and secondly individual data in a multivariate regression model.Results:Individual data from 8 RCTs, 2 on infliximab (n=1477) and 6 on golimumab (total =3041) were obtained. In the aggregate model analysis, none of the selected factors had a significant impact on clinical response. In the multivariate analysis, male sex and physical activity were significantly associated with a lower DAS28-CRP after 6 months of treatment (regression coefficients -0.264 (p<0.001) and -0.193 (p=0.004) respectively), while a high initial DAS28-CRP was significantly associated with a higher DAS28-CRP (regression coefficient 0.579 (p<0.001)). The baseline disease activity was the only significant interaction factor with the effect of the treatment.Conclusion:Male gender and practicing physical activity are associated with lower disease activity 6 months after golimumab or infliximab initiation. High baseline disease activity significantly influences negatively the effect of the treatment on disease activity score.Acknowledgements:This study, carried out under YODA Project 2018-2931, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.Disclosure of Interests:Marc-Antoine SPARFEL: None declared, Sophie Derolez: None declared, Johan Law-Wan: None declared, Nicolas Azzopardi: None declared, Philippe Goupille Speakers bureau: Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, Consultant of: Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, Grant/research support from: Clinical trials sponsored by Abbvie, Roche, BMS, Boehringer, Lilly, Novartis, Pfizer, UCB, Janssen and MSD. Invitation to an international congresses by MSD, Roche, BMS and Abbvie, Denis Mulleman Speakers bureau: Pfizer and Novartis, Consultant of: Pfizer and Novartis, Grant/research support from: Invitation to an international congress by Janssen-Cilag, Theodora Bejan-Angoulvant: None declared

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A Historic Moment for Open Science: The Yale University Open Data Access Project and Medtronic

Annals of Internal Medicine ◽

10.7326/0003-4819-158-12-201306180-00009 ◽

2013 ◽

Vol 158 (12) ◽

pp. 910 ◽

Cited By ~ 34

Author(s):

Harlan M. Krumholz ◽

Joseph S. Ross ◽

Cary P. Gross ◽

Ezekiel J. Emanuel ◽

Beth Hodshon ◽

...

Keyword(s):

Open Data ◽

Data Access ◽

Open Science ◽

Yale University ◽

Access Project

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POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3126 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 900.1-900

Author(s):

L. Diebold ◽

T. Wirth ◽

V. Pradel ◽

N. Balandraud ◽

E. Fockens ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Disease Activity ◽

Univariate Analysis ◽

Route Of Administration ◽

Anxiety And Depression ◽

Administration Route ◽

Factors Associated ◽

The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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POS0407 PROTEOMICS ANALYSIS COMPARING THE MODE OF ACTION OF UPADACITINIB BETWEEN NON-BIOLOGIC-DMARD-IR AND BIOLOGIC-DMARD-IR PsA PATIENTS IDENTIFIES DISTINCT PATHOGENIC PATHWAYS IN THE SELECT-PsA 1 AND SELECT-PsA 2 PHASE 3 STUDIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1652 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 433.1-433

Author(s):

T. Sornasse ◽

J. Anderson ◽

K. Kato ◽

A. Lertratanakul ◽

I. McInnes ◽

...

Keyword(s):

Disease Activity ◽

Clinical Response ◽

Rheumatic Diseases ◽

Inadequate Response ◽

Protein Biomarkers ◽

Research Support ◽

Positive Correlation ◽

Disease Biology ◽

Biologic Dmard ◽

Favorable Clinical Response

Background:Treatment of non-biologic-DMARD-IR1 (DMARD-IR) and biologic-DMARD-IR2 (bio-IR) PsA patients with upadacitinib (UPA) at 15 mg QD, an oral JAK1 selective inhibitor, resulted in significant improvement in signs and symptoms compared to placebo.Objectives:Using a pre-defined set of inflammation-related plasma protein biomarkers (pBM), to explore immunological pathway modulation by UPA 15 mg QD in PsA patients with active disease despite treatment with non-biologic or biologic DMARDs in the context of clinical response vs. non-response to treatment.Methods:Patients from the SELECT-PsA 1 (DMARD-IR) and the SELECT-PsA 2 (bio-IR) studies were randomly selected (PBO, n=100; UPA 15 mg QD, n=100 for each study). The levels of 92 inflammation related protein biomarkers (pBM) were analyzed using a multiplexed Proximity Extension Assay platform in plasma samples collected at baseline, week 2, and 12; change from baseline in protein levels was expressed as Log2 Fold Change; a Repeated Measure Mixed Linear Model was used to identify pBM modulated by UPA compared to Baseline, and those differentially modulated between responders (R) and non-responders (NR) according to ACR50, PASDAS Minimal Disease Activity, and PASI75 at week 12. Correlation of disease activity measures with relative levels of pBM were derived using Pearson’s correlation; PASI score was transformed as Log10 (x+1) prior to the analysis. Functional pathway prediction was performed in silico with a commercial distributed software.Results:At baseline, the relative levels of 37 pBM correlated with at least one baseline disease activity measure, with a marked positive correlation of IL6 with musculoskeletal end points (PASDAS and DAS28CRP), and a strong positive correlation of IL20, IL17A, IL17C, and TGFA with baseline PASI.At the single pBM-level, treatment with UPA 15 mg QD resulted in a down modulation of pBM associated with T cells, myeloid cells, and IFN-, IL6-, and TNF-related pathways in both DMARD-IR and bio-IR PsA patients. Overall effects of UPA on single pBMs were broadly similar between DMARD-IR and bio-IR patients. However, analysis of pBMs differentially modulated by UPA in R vs NR indicated that favorable clinical response (achievement of ACR50, PASDAS MDA, and PASI75) in DMARD-IR patients was associated with the down modulation of pBMs predicted to be linked to IFN, IL10, IL17, IL22, and IL27 pathways; while favorable clinical response in bio-IR patients was associated with the down modulation of multiple pBM predicted to be linked to the IL17, IL23, and IL1 pathways.Conclusion:UPA effects in both DMARD-IR and bio-IR PsA patients likely stem from the direct and indirect inhibition of multiple biological pathways belonging to the adaptive and innate immune systems. Responder/Non-Responder analysis suggests a possible shift from a TH1 biased biology in DMARD-IR PsA patients to a more TH17 biased biology in bio-IR PsA patients. This apparent change in the disease biology of PsA patients after inadequate response to prior therapy could be attributed to the actual alteration of the disease biology, treatment outcome-based patient selection, or both. Considering the clinical efficacy of UPA in both DMARD-IR and bio-IR PsA patients, this observation highlights the importance of targeting multiple pathways with drugs such as UPA for the treatment of a broad range of PsA patients.References:[1]McInnes, I. et al. Annals of the Rheumatic Diseases 79, 16-17 (2020).[2]Mease, P.J. et al.Annals of the Rheumatic Diseases, annrheumdis-2020-218870 (2020).Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Disclosure of Interests:Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB

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P181 Long-term improvement in axial spondyloarthritis clinical outcomes following 2-weeks of intensive education and rehabilitation: results from the Bath residential rehabilitation programme

Rheumatology ◽

10.1093/rheumatology/keab247.176 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Rosie Barnett ◽

Anita McGrogan ◽

Matthew Young ◽

Charlotte Cavill ◽

Mandy Freeth ◽

...

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Disease Activity ◽

Axial Spondyloarthritis ◽

Rehabilitation Programme ◽

Spinal Mobility ◽

The Impact

Abstract Background/Aims Axial spondyloarthritis (axSpA) is a chronic rheumatic condition, characterised by inflammatory back pain - often associated with impaired function and mobility, sleep disturbance, fatigue, and reduced quality of life. Despite the vast advances in pharmacological treatments for axSpA over the last few decades, physical activity and rehabilitation remain vital for effective disease management. At the Royal National Hospital for Rheumatic Diseases in Bath (RNHRD), the 2-week inpatient axSpA rehabilitation programme has been integral to axSpA care since the 1970’s. Prior research has demonstrated significant short-term improvements in spinal mobility (BASMI), function (BASFI) and disease activity (BASDAI) following course attendance. However, the long-term outcomes are yet to be evaluated in this unique cohort. Methods Since the early 1990’s, clinical measures of spinal mobility, function and disease activity have been routinely collected at the RNHRD at all clinical appointments through administration of the BASMI, BASFI and BASDAI, respectively. Dates of attending the axSpA course and standard clinical and treatment follow-up data were also collected. Multiple linear regression models were used to investigate the impact of course attendance on final reported BASMI, BASDAI and BASFI scores (final score=most recent). Length of follow-up was defined as time between first and last recorded BASMI. Results Of the 203 patients within the Bath SPARC200 cohort, 77.8% (158/203) had attended at least one rehabilitation course throughout follow-up. 70.0% (140/203) of patients were male. The mean duration of follow-up was 13.5 years (range 0-35 years); 28.1% (57/203) of individuals with 20+ years of follow-up. Course attendance (yes versus no) significantly reduced final BASMI score by 0.84 (p = 0.001, 95%CI -1.31 to -0.37) and final BASDAI score by 0.74 (p = 0.018, 95%CI -1.34 to -0.13). Although course attendance reduced final BASFI by 0.45 (95%CI -1.17 to 0.28), this relationship did not reach significance (p = 0.225). Whilst minimally clinically important difference (MCID) is, to our knowledge, yet to be defined for BASMI, MCIDs were achieved long-term for both BASDAI and BASFI - defined by van der Heijde and colleagues in 2016 as 0.7 and 0.4 for BASDAI and BASFI, respectively. Conclusion These results provide novel evidence to support the integral role of education, physical activity and rehabilitation in the management of axSpA. Future work should investigate additional outcomes of critical importance to patients and clinicians, such as fatigue, quality of life and work productivity. Furthermore, a greater understanding of the factors that confound these outcomes may provide insights into those patients who may most benefit from attending a 2-week rehabilitation course. In addition to facilitating identification of those patients who may require additional clinical support. Disclosure R. Barnett: None. A. McGrogan: None. M. Young: None. C. Cavill: None. M. Freeth: None. R. Sengupta: Honoraria; Biogen, Celgene, AbbVie, Novartis, MSD. Grants/research support; Novartis, UCB.

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FRI0300 ARE COPING STRATEGIES, ANXIETY AND DEPRESSION ASSOCIATED WITH DAILY PHYSICAL ACTIVITY IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2724 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 739-739

Author(s):

M. Carbo ◽

L. Overbeeke ◽

S. Arends ◽

Y. Kamsma ◽

F. Wink ◽

...

Keyword(s):

Physical Activity ◽

Coping Strategies ◽

Coping Strategy ◽

Axial Spondyloarthritis ◽

Depression Scale ◽

Daily Physical Activity ◽

Anxiety And Depression ◽

Research Support ◽

Related Factors

Background:Patients with axial spondyloarthritis (axSpA) who are more physically active experience less pain and better physical functioning.1Psychological factors such as anxiety and depression are associated with physical functioning and reduction of Quality of Life (QoL).2Furthermore, evasive coping strategies are commonly used in health-related coping.3However, as far as we know, no data is available regarding the influence of coping strategies, anxiety and depression on daily physical activity in axSpA.Objectives:To determine if coping strategies, anxiety and depression are associated with daily physical activity in patients with axSpA.Methods:Consecutive outpatients from the Groningen Leeuwarden AxSpA cohort (GLAS) participated in this study. Additionally to the standardized follow-up assessments, patients filled out the axSpA-Short Questionnaire to assess health-enhancing physical activity (axSpA-SQUASH), the Coping with Rheumatic Stressors (CORS) and the Hospital Anxiety and Depression Scale (HADS). Univariable and multivariable linear regression analyses were performed to explore associations of copings strategies, anxiety and depression, and patient- and disease related factors with daily physical activity. Additionally, patients were stratified into three tertiles of physical activity: low, intermediate and high. To identify group differences, Kruskal-Wallis test or Chi-Square test were used with post-hoc testing.Results:In total 85 patients were included; 59% were male, mean age was 49±14, median symptom duration 19.5 years (IQR 12.0-31.0), 71% were HLA-B27 positive and mean ASDAS was 2.1±1.0. Median axSpA-SQUASH total physical activity score was 9406.3 (IQR 5538.8–12081.3). Median scores of HADS-Anxiety (scale 7-28) and HADS-Depression (scale 7-28) were scores of 12 (IQR 10.0-14.0) and 10(IQR 9.0-12.5). The mostly frequently used coping strategie was comforting cognitions (for pain, range 9-36); median of 25.5 (IQR 22.0-28.0).Univariable analysis showed that lower daily physical activity was significantly associated with gender (female), higher disease activity (BASDAI), worse physical function (BASFI), worse quality of life (ASQoL), coping strategies ‘decreasing activities’ and ‘pacing’, higher depression score (HADS) and higher perceived influence of axSpA on general well-being. In multivariable analysis, only the coping strategy “decreasing activity” was independently associated with physical activity (β: -419.3, R2: 0.155, P<0.001). Additionally, patients in the highest physical activity tertile were significantly more often male, had higher working status, lower BASDAI and ASDAS, better BASFI and ASQoL and scored lower on the coping strategy “decreasing activities”.Conclusion:In this cross-sectional study in axSpA patients with established disease, multiple patient and disease related factors were associated with daily physical activity. The evasive coping strategy ‘decreasing activities’ was the only independently associated factor. These findings suggest that to improve daily physical activity in axSpA patients attention should be paid not only on targeting disease activity, but also to other patient and disease related aspects, especially coping strategies used.References:[1]Regel A et al.RMD Open. 2017;3(1):e000397.[2]Kilic G et al.Med (United States). 2014;93(29):e337.[3]Peláez-Ballestas I et al.Med (United States). 2015;94(10):e600.Acknowledgments:The authors would like to thank all patients who participated in the GLAS cohort.Disclosure of Interests:Marlies Carbo: None declared, Laura Overbeeke: None declared, Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Yvo Kamsma: None declared, Freke Wink Consultant of: Abbvie, Janssen, Davy Paap: None declared, Anneke Spoorenberg: None declared

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OP0131 ANIFROLUMAB EFFECTS ON RASH AND ARTHRITIS IN PATIENTS WITH SLE AND IMPACT OF INTERFERON SIGNAL IN POOLED DATA FROM PHASE 3 TRIALS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1471 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 75-76

Author(s):

J. T. Merrill ◽

V. Werth ◽

R. Furie ◽

E. F. Morand ◽

J. M. Kahlenberg ◽

...

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Small Sample ◽

Type I ◽

Research Support ◽

Phase 3 ◽

Pooled Data ◽

Link Type ◽

The Impact

Background:Treatment with the type I interferon (IFN) receptor antibody anifrolumab was associated with clinical improvements in mucocutaneous and musculoskeletal disease activity in patients with systemic lupus erythematosus (SLE) in the phase 2 MUSE trial (NCT01438489) and phase 3 TULIP trials.1–4 Because rash and arthritis are the most common manifestations of SLE, the effect of anifrolumab on these symptoms can be examined in biomarker-defined subsets, as previously reported for the MUSE trial.2Objectives:To evaluate the effect of anifrolumab on rash and arthritis in patients with SLE, and the impact of IFN gene signature (IFNGS) on treatment response, using disease measures of different stringency in pooled data from the phase 3 TULIP trials.Methods:TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were placebo-controlled, 52-week trials of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE.3,4 In this post hoc analysis, outcomes of rash and arthritis were evaluated using mucocutaneous and musculoskeletal domains of the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) index. In addition, the modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) score was used to evaluate rash, and tender and swollen joint counts were used to assess arthritis.Results:360 patients received anifrolumab 300 mg (IFNGS test–high, n=298; IFNGS test–low, n=62) and 366 patients were given placebo (IFNGS test–high, n=302; IFNGS test–low, n=64). Change from baseline to Week 52 compared with placebo was measured by outcomes, ordered by their stringency. More anifrolumab-treated patients achieved rash improvement using SLEDAI-2K (complete resolution: difference 13.5%, nominal P<0.001), BILAG (at least 1 severity grade lowering: difference 15.5%, nominal P<0.001), and mCLASI (≥50% improvement, if baseline score >0: difference 15.6%, nominal P<0.001). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 17.0%, nominal P<0.001, BILAG: difference 16.1%, nominal P<0.001; mCLASI: difference 18.1%, nominal P<0.001). There was a trend toward anifrolumab-associated rash improvement in IFNGS test–low patients using BILAG (Figure). More patients receiving anifrolumab had SLEDAI-2K–defined resolution in arthritis (difference 8.2%, nominal P=0.029), BILAG severity lessening (difference 11.8%, nominal P=0.002), and ≥50% decrease in tender/swollen joint counts, when ≥6 at baseline (difference 12.6%, nominal P=0.016). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 11.7%, nominal P=0.005; BILAG: difference 12.9%, nominal P=0.003; joint counts: difference 11.3%, nominal P=0.054). In IFNGS test–low patients, there was a trend toward anifrolumab-associated arthritis improvement when measured using BILAG, and the effect of anifrolumab on the number of swollen/tender joint counts was similar to the IFNGS test–high group, although the IFNGS test–low sample size in this analysis was very small (Figure).Conclusion:In pooled data from the TULIP trials, anifrolumab treatment was associated with improvements in rash and arthritis using measures of different stringency. The SLEDAI-2K findings were largely driven by the subset of patients who were IFNGS test–high. However, using measures that were more sensitive to change, despite small sample sizes, IFNGS test–low patients may also have benefit.References:[1]Furie R, et al. Arthritis Rheumatol. 2017;69:376–86.[2]Merrill JT, et al. Lupus Sci Med. 2018;5:e000284.[3]Furie RA, et al. Lancet Rheumatol. 2019;1:e208–19.[4]Morand EF, et al. N Engl J Med. 2020;382:211–21.Acknowledgements:Writing assistance by Victoria Alikhan, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.Disclosure of Interests:Joan T Merrill Consultant of: AstraZeneca, AbbVie, Amgen, Aurinia, BMS, EMD Serono, GSK, Remegen, Janssen, Provention, and UCB, Grant/research support from: BMS and GSK, Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, J Michelle Kahlenberg Consultant of: Admirex Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, BMS, Boehringer Ingelheim, Eli Lilly, and Ventus Therapeutics, Grant/research support from: BMS/Celgene and Q32 Bio, Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

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Metabolomic Profiling Identifies Exogenous and Microbiota-Derived Metabolites as Markers of Methotrexate Efficacy in Juvenile Idiopathic Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.768599 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ryan Sol Funk ◽

Mara L. Becker

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Clinical Response ◽

Enrichment Analysis ◽

P Value ◽

Metabolomic Profiling ◽

Plasma Metabolome ◽

Unsaturated Triglycerides ◽

Metabolic Biomarkers ◽

The Impact

Variability in methotrexate (MTX) efficacy represents a barrier to early and effective disease control in the treatment of juvenile idiopathic arthritis (JIA). This work seeks to understand the impact of MTX on the plasma metabolome and to identify metabolic biomarkers of MTX efficacy in a prospective cohort of children with JIA. Plasma samples from a cohort of children with JIA (n = 30) collected prior to the initiation of MTX and after 3 months of therapy were analyzed using a semi-targeted global metabolomic platform detecting 673 metabolites across a diversity of biochemical classes. Disease activity was measured using the 71-joint count juvenile arthritis disease activity score (JADAS-71) and clinical response to MTX was based on achievement of ACR Pedi 70 response. Metabolomic analysis identified 50 metabolites from diverse biochemical classes that were altered following the initiation of MTX (p < 0.05) with 15 metabolites reaching a false-discovery rate adjusted p-value (q-value) of less than 0.05. Enrichment analysis identified a class-wide reduction in unsaturated triglycerides following initiation of MTX (q = 0.0009). Twelve of the identified metabolites were significantly associated with disease activity by JADAS-71. Reductions in three metabolites were found to be associated with clinical response by ACR Pedi 70 response criteria and represented several microbiota and exogenously derived metabolites including: dehydrocholic acid, biotin, and 4-picoline. These findings support diverse metabolic changes following initiation of MTX in children with JIA and identify metabolites associated with microbial metabolism and exogenous sources associated with MTX efficacy.

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Characteristics of available studies and dissemination of research using major clinical data sharing platforms

Clinical Trials ◽

10.1177/17407745211038524 ◽

2021 ◽

pp. 174077452110385

Author(s):

Enrique Vazquez ◽

Henri Gouraud ◽

Florian Naudet ◽

Cary P Gross ◽

Harlan M Krumholz ◽

...

Keyword(s):

Open Access ◽

Data Sharing ◽

Clinical Data ◽

Open Data ◽

Data Access ◽

Data Repository ◽

Biological Specimen ◽

Research Findings ◽

Access Project ◽

Project Data

Background/Aims: Over the past decade, numerous data sharing platforms have been launched, providing access to de-identified individual patient-level data and supporting documentation. We evaluated the characteristics of prominent clinical data sharing platforms, including types of studies listed as available for request, data requests received, and rates of dissemination of research findings from data requests. Methods: We reviewed publicly available information listed on the websites of six prominent clinical data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center, ClinicalStudyDataRequest.com , Project Data Sphere, Supporting Open Access to Researchers–Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project. We recorded key platform characteristics, including listed studies and available supporting documentation, information on the number and status of data requests, and rates of dissemination of research findings from data requests (i.e. publications in a peer-reviewed journals, preprints, conference abstracts, or results reported on the platform’s website). Results: The number of clinical studies listed as available for request varied among five data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center (n = 219), ClinicalStudyDataRequest.com (n = 2,897), Project Data Sphere (n = 154), Vivli (n = 5426), and the Yale Open Data Access Project (n = 395); Supporting Open Access to Researchers did not provide a list of Bristol Myers Squibb studies available for request. Individual patient-level data were nearly always reported as being available for request, as opposed to only Clinical Study Reports (Biological Specimen and Data Repository Information Coordinating Center = 211/219 (96.3%); ClinicalStudyDataRequest.com = 2884/2897 (99.6%); Project Data Sphere = 154/154 (100.0%); and the Yale Open Data Access Project = 355/395 (89.9%)); Vivli did not provide downloadable study metadata. Of 1201 data requests listed on ClinicalStudyDataRequest.com , Supporting Open Access to Researchers–Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project platforms, 586 requests (48.8%) were approved (i.e. data access granted). The majority were for secondary analyses and/or developing/validating methods ( ClinicalStudyDataRequest.com = 262/313 (83.7%); Supporting Open Access to Researchers–Bristol Myers Squibb = 22/30 (73.3%); Vivli = 63/84 (75.0%); the Yale Open Data Access Project = 111/159 (69.8%)); four were for re-analyses or corroborations of previous research findings ( ClinicalStudyDataRequest.com = 3/313 (1.0%) and the Yale Open Data Access Project = 1/159 (0.6%)). Ninety-five (16.1%) approved data requests had results disseminated via peer-reviewed publications ( ClinicalStudyDataRequest.com = 61/313 (19.5%); Supporting Open Access to Researchers–Bristol Myers Squibb = 3/30 (10.0%); Vivli = 4/84 (4.8%); the Yale Open Data Access Project = 27/159 (17.0%)). Forty-two (6.8%) additional requests reported results through preprints, conference abstracts, or on the platform’s website ( ClinicalStudyDataRequest.com = 12/313 (3.8%); Supporting Open Access to Researchers–Bristol Myers Squibb = 3/30 (10.0%); Vivli = 2/84 (2.4%); Yale Open Data Access Project = 25/159 (15.7%)). Conclusion: Across six prominent clinical data sharing platforms, information on studies and request metrics varied in availability and format. Most data requests focused on secondary analyses and approximately one-quarter of all approved requests publicly disseminated their results. To further promote the use of shared clinical data, platforms should increase transparency, consistently clarify the availability of the listed studies and supporting documentation, and ensure that research findings from data requests are disseminated.

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Impacto de los hábitos sobre la mineralización ósea durante la etapa de la juventud

Revista Colombiana de Endocrinología, Diabetes & Metabolismo ◽

10.53853/encr.2.4.48 ◽

2017 ◽

Vol 2 (4) ◽

pp. 33-37

Author(s):

Paola Orozco Santos ◽

John Jairo Duque ◽

Juan Carlos Lucas

Keyword(s):

Physical Activity ◽

Bone Mass ◽

Clinical Record ◽

Z Score ◽

Mineralization Process ◽

Related Factors ◽

Nutritional Factors ◽

Gradual Loss ◽

The Impact

Los mayores picos de mineralización se producen en los primeros 2 años de vida y la pubertad, en los que la masa ósea aumenta 40% y 60%; a los 20 años se estabiliza y, luego, se inicia una pérdida progresiva. El volumen de masa ósea es variable según la edad, el sexo y la raza, es afectado por factores ambientales, genéticos, hormonales y nutricionales. El objetivo del estudio fue conocer el impacto de los hábitos relacionados con el proceso de mineralización durante la etapa de la juventud. Los participantes completaron una ficha clínica. La densidad mineral ósea fue valorada por medio de densitometría, se midieron los niveles de calcio en orina para identificar posibles pérdidas, se calculó el índice de masa corporal (IMC) a partir del peso y la talla. El 5% de la población participante presentó un Z-score inferior a -2,0 y los factores relacionados fueron consumo de cafeína, alcohol y poca actividad física.Abstract The highest peaks of mineralization is in the first two years of life and puberty, bone mass increases 40% to 60%, at twenty stabilizes and begins a gradual loss. The volume of bone mass varies according to age, sex and race, which affect environmental, genetic, hormonal and nutritional factors. The aim of the study was to determine the impact of the habits related mineralization process during the stage of youth. Participants completed clinical record. BMD was assessed by densitometry; Calcium levels were measured in urine for loss, BMI was calculated from weight and height. 5% of the participating population present a Z-score less than -2,0 and related factors were caffeine, alcohol and little physical activity.

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DOP01 Exclusive enteral nutrition for the treatment of adult Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.040 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S041-S041

Author(s):

D Shukla ◽

L Purcell ◽

M Palmer ◽

L Pillay

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Disease Activity ◽

Cell Count ◽

Clinical Response ◽

White Cell Count ◽

White Cell ◽

Exclusive Enteral Nutrition ◽

The Impact

Abstract Background Crohn’s disease (CD) is a debilitating autoimmune disease affecting >40 000 Australians. Exclusive enteral nutrition (EEN) is an effective, risk-free therapy in children with CD, offering an ~80% success rate. Despite similar efficacy in adults, including the potential to decrease the need for high-risk steroids and surgery, adherence remains an unresolved obstacle for its use, with withdrawal rates of up to 40% (Wall 2013). Lack of dietetic expertise and support for adults on EEN were identified as primary barriers (Wall 2013). This prospective, single-centre, observational study aimed to assess the impact of a 6-week EEN model of care on disease symptoms, nutrition and inflammatory markers. We also assessed if >80% of adults with CD could adhere to EEN. Methods Adults with active CD were treated with oral EEN for six weeks between March 2018 and September 2019 which uniquely included weekly specialist Dietetic support. EEN is the provision of 100% of a patient’s nutritional requirements via a nutritionally complete liquid formula. Paired assessment at baseline and EEN completion occurred for Crohn’s disease activity index (CDAI), calprotectin, C-reaction protein (CRP), platelets, albumin, white cell count, weight and calprotectin using paired t-tests. The primary outcome measure was disease activity using CDAI. Results Twenty-seven eligible CD patients were identified. Most patients (85%, n = 23/27) successfully adhered to EEN treatment (45 ± 13 years, 63% female, 52% had Calprotectin ≥100). The patients were further subdivided as per Montreal classification (L1:n = 12; L2:n = 3; L3:n = 12) and 93% were on medications such as steroids (n = 9/27), immunosuppressives (n = 19/27) and biologics (n = 16/27). After EEN, 74% (n = 20/27) achieved clinical remission (CDAI <150) 19/27 patients (70%) achieved clinical response with >70-point reduction in CDAI score and most (77%) patients achieved greatest improvement in CDAI score in the well-being section. A trend showed that 37% (p = 0.087) more patients with L2 and L3 CD achieved clinical response through CDAI than L1 CD patients. Calprotectin also showed a trend for improvement (-23(-65230-150) µg, p = 0.067, n = 20). No differences were observed in CRP, white cell count, or albumin (p = 0.262–0.433, n = 12–13); however, platelets showed a trend for improvement (-26(-156-46) µl, p = 0.071, n = 12) and weight reduced by −2.4(3.2) kg (p = 0.001). Few (30%, n = 8/27) patients changed medications during EEN treatment. No significant side effects were observed. Conclusion EEN may be achievable for most adults with additional professional support and has merit in assisting patients with clinical improvement of CD.

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