OP0288 ANTI-IL1 TREATMENT IN COLCHICINE RESISTANT PEDIATRIC FMF PATIENTS-REAL LIFE DATA FROM THE HELIOS REGISTRY

Background:FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine resistant/intolerant FMF patients.Objectives:We aimed to investigate the efficacy and safety of anti-IL1 treatment in pediatric FMF patients in our local (HELIOS) registry.Methods:HELIOS (Hacettepe univErsity eLectronIc research fOrmS) is a web-based biological drug registry for pediatric rheumatology patients (helios.hacettepe.edu.tr). Data were recorded at biological treatment onset (month 0), at month 6 and yearly thereafter in patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agent.Results:Forty pediatric FMF patients were included to the study group (67% female).Thirty-four patients received continous anti-IL1 treatment. The mean age at the start of the colchicine was 5.55±3.87 years. Age at onset of the anti-IL1 treatment was 11.47±5.41 with a mean follow-up duration of 3.87±1.96 years. Apart from two patients, all of them had biallelic exon-10 mutations.We have also given anti-IL1 treatment on an on-demand basis in six adolescent patients. Five of them were having very severe attacks during menstrual periods and one was having attacks during extreme stress periods along with very high CRP levels. The quality of life has markedly improved and these patients no longer reveal any CRP elevation.Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients were treated with canakinumab. Anti-IL1 treatment decreased the CRP levels, number and severity of the attacks. (Figure 1.) There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leukopenia with anakinra and one patient had thrombocytopenia with canakinumab. We have discontinued anti-IL1 treatment until the cytopenia subsided. We have switched to on-demand therapy in one patient, started the same treatment and gradually increased the dose in the other two patients. There were no malignancy or other severe adverse reactions.Figure 1.Conclusion:Anakinra and canakinumab are efficient and safe alternatives in colchicine resistant and intolerant pediatric FMF patients. We also for the first time, report on-demand use of anti-IL1 in pediatric FMF patients. We suggest that on-demand treatment should be considered under certain circumstances where the trigger is known and short-lasting (such as menstruation and periods of extreme stress)Acknowledgments:Authors would like to thank Elif Arslanoglu Aydin, Armagan Keskin, Kubra Yuksel and Emil Aliyev for their contribution to the HELIOS registryDisclosure of Interests:Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Fuat Akal Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Erdal Atalay Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ummusen Kaya Akca Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Selcan Demir Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Dilara Demirel Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ezgi Deniz Batu Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis

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Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry

Rheumatology ◽

10.1093/rheumatology/keaa121 ◽

2020 ◽

Vol 59 (11) ◽

pp. 3324-3329 ◽

Cited By ~ 1

Author(s):

Erdal Sag ◽

Fuat Akal ◽

Erdal Atalay ◽

Ummusen Kaya Akca ◽

Selcan Demir ◽

...

Keyword(s):

Age At Onset ◽

Real Life ◽

Treated Group ◽

First Line ◽

Skin Reactions ◽

Web Based ◽

Local Skin ◽

On Demand ◽

Real Life Data ◽

Drug Registry

Abstract Objectives FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry. Methods HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents. Results Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions. Conclusion Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.

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THU0386 PREDICTORS OF MAINTENANCE OF SECUKINUMAB TREATMENT IN A MULTICENTER COHORT OF 561 SPONDYLARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4713 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 427.1-428

Author(s):

B. Flachaire ◽

J. G. Letarouilly ◽

C. Labadie ◽

N. Cohen ◽

V. Pradel ◽

...

Keyword(s):

Clinical Practice ◽

Smoking Status ◽

Safety Issue ◽

Real Life ◽

Routine Clinical Practice ◽

Interleukin 17 ◽

Sustained Remission ◽

Concomitant Treatment ◽

First Line ◽

Research Support

Objectives:Secukinumab (SEC) is an interleukin-17 inhibitor used to treat patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Drug maintenance is often used as a proxy for treatment effectiveness and safety in real life settings. We aim to assess SEC maintenance in routine clinical practice and to identify survival predictors associated.Methods:We conducted a retrospective, longitudinal, observational, multicenter study including all patients (pts) with axSpA or PsA who received at least 1 injection of SEC between July 2016 and October 2019. We collected patient’s demographics and clinic characteristics, SEC date of initiation and dosage and dosage modification of SEC, previous biologic Disease-modifying antirheumatic drugs (bDMARDs) and concomitant treatments. Date and reasons of discontinuation – i.e., lack of efficacy, safety issue, sustained remission or others – were collected. Several potential maintenance predictors were tested: age, gender, disease (axSpA or PsA), smoking status, bDMARDs history and concomitant treatment. Among patients with non-radiographic axSpA (nr-axSpA), evidence of MRI sacroiliitis or elevated CRP were also assessed as potential maintenance predictors. Drug maintenance was analyzed by the Kaplan-Meier method and adjusted for baseline factors were estimated by log rank analysis.Results:The main characteristics of the 561 pts included were the following: 363 (64.7%) axSpA, 198 (35.3%) PsA, 329 (58.6%) female, mean age 45,6 +/- 12 years, 221 (39.4%) smokers, 175 (31.2%) radiographic sacroiliitis, 259 (46.2%) MRI sacroiliitis, 198 (35.3%) elevated CRP, 247 (44.0%) HLA B27 positive, mean BASDAI 48,3 +/- 26.8%. SEC was associated to methotrexate (MTX) in 139 pts (24.8%) and was the first line bDMARD in 55 pts (9.8%). The median drug maintenance (MDM) of SEC was 79 weeks (wk) [73-84]. At 52 wk, 245 pts (60%) SpA were still treated with SEC. During the 3-year follow-up, 264 pts discontinued SEC: 180 (68.2%) pts for lack of effectiveness, 47 (17.8%) for adverse events, 14 (5.3%) for others and 23 (8.7%). SEC prescription as first line bDMARD was associated with longer survival versus second line or more: 111 wk [83-138] vs. 69 wk [57-80] (p=0. 017) (figure 1). MDM was not significantly different depending on gender, MTX combo, elevated CRP, axSpA vs PsA and smoking status. Among the nr-axSpA pts, MRI sacroiliitis or elevated CRP did not modify SEC maintenance (p=0.68) (figure 2).Figure 1.Secukinumab maintenance according to therapeutic lineFigure 2.Secukinumab maintenance in nr-axSpA populationConclusion:In routine clinical practice, SEC median maintenance was 79 weeks. Fist line administration was the only independent factor associated with improved SEC retention. Lack of effectiveness was the most common reason of discontinuation.Disclosure of Interests:Benoît Flachaire: None declared, Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Vincent Pradel: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Guy Baudens: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Corinne Miceli Richard: None declared, Philippe Dieudé: None declared, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Jérémie SELLAM: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Marie-Hélène Guyot: None declared, Chi Duc Nguyen: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Thao Pham Speakers bureau: Novartis, Janssen, Lilly

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2928 ◽

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

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4184 ◽

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

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AB0369 EFFICACY AND SAFETY OF RITUXIMAB ORIGINATOR AND BIOSIMILAR IN PRIMARY SJÖGREN’S SYNDROME IN A REAL-LIFE SETTING

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6608 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1485.3-1485

Author(s):

F. Carubbi ◽

A. Alunno ◽

P. Cipriani ◽

V. Pavlych ◽

C. DI Muzio ◽

...

Keyword(s):

Disease Activity ◽

Real Life ◽

Primary Sjögren’S Syndrome ◽

Efficacy And Safety ◽

Research Support ◽

Treatment Groups ◽

Real Life Setting ◽

Patient Reported ◽

Time Point

Background:Over the last 2 decades rituximab (RTX) has been widely used, albeit off-label, in primary Sjögren’s syndrome (pSS). Several studies reported that B-lymphocyte depletion with RTX is effective in this disease not only by reducing disease activity but also by affecting the inflammation and the lymphoid organization that occur in target tissues. With the recent release of several RTX biosimilars (bRTX) on the market, the demonstration of their interchangeability with RTX originator (oRTX) is required.Objectives:To compare efficacy and safety of oRTX and bRTX in pSS patients in a real-life setting.Methods:Clinical records of pSS patients referring to a tertiary rheumatology clinic were retrospectively evaluated. Patients having received at least 2 courses of either oRTX or bRTX (1000 mg IV infusion, repeated after 2 weeks -1 course- and the course repeated after 24 weeks) with complete data at baseline and after 3, 6, 9 and 12 months of treatment were enrolled. Disease activity was assessed with the EULAR SS disease activity index (ESSDAI) and its clinical version without the biological domain (ClinESSDAI). Patient-reported symptoms were assessed with the EULAR SS Patient Reported Index (ESSPRI).Results:Seven patients that received oRTX and 7 patients that received bRTX were enrolled. Baseline clinical features, including ESSDAI and ESSPRI were similar in the 2 treatment groups. Both compounds significantly reduced ESSDAI and ESSPRI as early as 3 months and no difference between the groups was observed at any time point (Figure 1). Of interest, ESSDAI slowly decreased until month 6 when the most pronounced reduction was observed. Conversely, ESSPRI dropped to its lowest values already at month 3. With regard to safety, at 12 months of follow-up no adverse event was observed in any of the treatment groups.Conclusion:At 12 months of follow-up, oRTX and bRTX display similar efficacy and safety profiles. The improvement of patient reported outcomes is faster than the improvement of disease activity with both compounds. Our data support interchangeability of oRTX and bRTX in pSS.References:[1]Carubbi F et al. Arthritis Res Ther. 2013;15(5):R172[2]Carubbi F et al. Lupus. 2014;23(13):1337-49Figure 1 ESSDAI and ESSPRI values at every time point in the 2 treatment groups. Asterisks indicate p values <0.05 compared to the other treatment group at the same time pointDisclosure of Interests:Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Alessia Alunno: None declared, Paola Cipriani Grant/research support from: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, Viktoriya Pavlych: None declared, claudia di muzio: None declared, Roberto Gerli: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5263 ◽

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

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17. Comparative Safety of Antibiotic Therapy for Outpatient Treatment of Uncomplicated Urinary Tract Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa417.016 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S9-S10

Author(s):

Anne M Butler ◽

Michael Durkin ◽

Matthew R Keller ◽

Yinjiao Ma ◽

William Powderly ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Abdominal Pain ◽

Urinary Tract ◽

Skin Rash ◽

Adverse Drug Events ◽

Vulvovaginal Candidiasis ◽

First Line ◽

Research Support ◽

Comparative Safety

Abstract Background Urinary tract infection (UTI) is one of the most common indications for outpatient antibiotic prescriptions in otherwise healthy women, yet the comparative safety of antibiotics for empirical therapy is not well established. We compared the risk of adverse drug events by antibiotic treatment regimen among premenopausal women with uncomplicated UTI. Methods Using the IBM MarketScan Commercial Database (2006–2015), we identified healthy, non-pregnant women aged 18–44 who were diagnosed with UTI and prescribed a same-day antibiotic with activity against common uropathogens. Patients were followed for outcomes with varying follow-up periods: 3 days (anaphylaxis), 14 days (acute renal failure, skin rash, urticaria/hives, nausea/vomiting, abdominal pain), 30 days (vaginitis/vulvovaginal candidiasis, non-C. difficile diarrhea) and 90 days (C. difficile diarrhea, pneumonia, tendinopathy, retinal detachment). We estimated propensity score-weighted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. Results Of 1,140,602 eligible women, the distribution of antibiotic receipt was fluoroquinolones (44%), trimethoprim-sulfamethoxazole (TMP/SMX) (28%), nitrofurantoin (24%), narrow-spectrum β-Lactam / β-Lactamase inhibitor combinations (“β-Lactams”) (3%), broad-spectrum β-Lactams (1%) and amoxicillin/ampicillin (1%). Of two first-line agents, we observed higher risk of outcomes among TMP/SMX vs. nitrofurantoin initiators: acute renal failure (HR 2.46, 95% CI 1.46–4.14), skin rash (HR 2.43, 95% CI 2.13–2.77), urticaria (HR 1.35, 95% CI 1.18–1.56), nausea/vomiting (HR 1.19, 95% CI 1.10–1.29) and abdominal pain (HR 1.14, 95% CI 1.09–1.19). Compared to nitrofurantoin, non-first-line agents (fluoroquinolones, broad-, and/or narrow-spectrum β-Lactams) were associated with higher risk of acute renal failure, skin rash, nausea/vomiting, abdominal pain, vaginitis/vulvovaginal candidiasis, diarrhea (C. difficile & non-C. difficile), pneumonia and tendinopathy. Conclusion The risk of adverse drug events differs widely by antibiotic agent, with substantial differences in first-line agents. Understanding antibiotic safety is critical to prevent suboptimal antibiotic prescribing and reduce adverse events. Disclosures Margaret A. Olsen, PhD, MPH, Merck (Grant/Research Support)Pfizer (Consultant, Grant/Research Support)

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Real-world clinical outcomes study of sequential novel antihormonal therapy (NAH) or radium-223 (Ra-223) treatment of metastatic castration-resistant prostate cancer (mCRPC) that progressed after first-line NAH.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.48 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 48-48

Author(s):

Oliver A. Sartor ◽

Daniel J. George ◽

Bertrand Tombal ◽

Celestia S. Higano ◽

Cora N. Sternberg ◽

...

Keyword(s):

Clinical Outcomes ◽

Real Life ◽

Patient Characteristics ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Highly Active ◽

Radium 223 ◽

Alpha Emitter ◽

Antihormonal Therapy ◽

The Usa

48 Background: We assessed real-life clinical outcomes in patients with mCRPC treated in the USA who received sequential first-line (1L)/second-line (2L) NAH (abiraterone/enzalutamide or enzalutamide/abiraterone) or switched to a different mechanism of action (alpha-emitter Ra-223) after progression on 1L NAH. Methods: This was a retrospective study (PHENIX, NCT03896984) of the Flatiron electronic health record database in patients with mCRPC that progressed on 1L NAH and started 2L monotherapy with Ra-223 (n=120) or NAH (n=226) between Jan 2013 and Dec 2018. Patient characteristics, overall survival (OS) from 2L start, and symptomatic skeletal events (SSEs) were analyzed descriptively. Results: The two cohorts were generally similar at 2L start, including similar rates of bone-health agent (BHA) use, but the Ra-223 cohort had a higher incidence of bone-only metastases, shorter duration of 1L NAH, and higher rate of prior SSEs than the 2L NAH cohort (Table). Median treatment duration was 5.6 mo (median 4.5 doses) for Ra-223 and 4.7 mo for 2L NAH. Median OS from 2L start was 10.8 mo for Ra-223 and 11.2 mo for 2L NAH, with 49% and 39%, respectively, receiving subsequent therapy. Among those who received subsequent therapy, the proportion who received subsequent taxane was lower in the Ra-223 cohort (47%) than in the 2L NAH cohort (76%). SSEs were observed after 2L start in 32 patients (27%) on Ra-223 and 49 (22%) on 2L NAH. Conclusions: OS from start of 2L mCRPC treatment was similar for patients who received Ra-223 or alternative NAH in 2L. Slightly more patients received subsequent therapy in the Ra-223 cohort than in the 2L NAH cohort. Patients who received subsequent therapy were more likely to receive chemotherapy in the 2L NAH cohort, which is unsurprising as 2L NAH after 1L NAH is not highly active. Although the prior SSE rate before 2L start was higher in the Ra-223 cohort than in the 2L NAH cohort, and the two cohorts had similar rates of BHA use at 2L start, the rate of SSEs after 2L start was similar in both cohorts. Clinical trial information: NCT03896984. [Table: see text]

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