THU0169 JANUS KINASE INHIBITORSDEMONSTRATE EFFECTIVENESS IN A REAL-WORLD MULTI-BIOLOGIC DMARD REFRACTORY RHEUMATOID ARTHRITIS POPULATION

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

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SAT0177 Real-world interruptions in janus kinase inhibitor therapy observed among biologic-naÏve and biologic-experienced rheumatoid arthritis patients

10.1136/annrheumdis-2018-eular.3456 ◽

2018 ◽

Author(s):

B. Chastek ◽

E. Koep ◽

U. G. Mallya ◽

A. Cockerham ◽

J. Choi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Real World ◽

Kinase Inhibitor ◽

Inhibitor Therapy ◽

Janus Kinase ◽

Janus Kinase Inhibitor

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Chronic Myeloid Leukemia in a Patient Receiving Tofacitinib: A Case Report and Literature Review

Case Reports in Rheumatology ◽

10.1155/2019/2814504 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Georgio Medawar ◽

Joseph Chahrouri ◽

Rabih Said

Keyword(s):

Rheumatoid Arthritis ◽

Case Report ◽

Myeloid Leukemia ◽

Kinase Inhibitor ◽

Janus Kinase ◽

Myelogenous Leukemia ◽

Janus Kinase Inhibitor ◽

Case Presentation ◽

Rheumatologic Diseases ◽

Refractory Rheumatoid Arthritis

Background. Tofacitinib is a new oral Janus kinase inhibitor that has shown promising clinical benefit in various rheumatologic diseases. However, many concerns related to the development of malignancies have been reported with its use. Case Presentation. A 43-year-old female patient received tofacitinib for refractory rheumatoid arthritis (RA). Two years after 5 mg bid daily dosing, the patient developed chronic myelogenous leukemia (CML), for which she received imatinib and tofacitinib was discontinued. She then remained in remission for rheumatoid arthritis and within the expected milestone outcome for her CML. Conclusion. This is the first reported case of CML after the use of tofacitinib. This event is of particular interest knowing the possible benefits tofacitinib carries in the treatment of CML demonstrated in a few studies.

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Predicting Response to Tocilizumab Monotherapy in Rheumatoid Arthritis: A Real-World Data Analysis Using Machine Learning

10.21203/rs.3.rs-79368/v1 ◽

2020 ◽

Author(s):

Fredrik D Johansson ◽

Jamie E Collins ◽

Vincent Yau ◽

Hongshu Guan ◽

Seoyoung C Kim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Logistic Regression ◽

Real World ◽

Prediction Models ◽

External Validation ◽

Similar Efficacy ◽

Prediction Score ◽

Real World Data ◽

World Data ◽

Biologic Dmard

Abstract Background Tocilizumab (TCZ) had similar efficacy when used as monotherapy or in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCT). Recently, we derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data. Herein, we describe external validation and several extensions of the prediction score using “real world data” (RWD).MethodsWe identified patients in Corrona-RA who used TCZm (n=453), matching the design and patients from four RCTs used in previous work (n=853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic DMARD monotherapies (bDMARDm) to improve prediction.ResultsThe fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n=53) in RWD vs 15% (n=127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTS with AUROC of 0.70 (95% CI 0.64, 0.77). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on TCZm patients to 0.73 (95% CI 0.64, 0.82). Extending the variable set and adding regularization further increased it to 0.77 (95% CI 0.68, 0.85).ConclusionThe remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD, including a larger variable set and learning from patients on similar therapies.

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AB0397 Abatacept shows better sustainability than tnf inhibitors when used following initial biologic dmard failure in the treatment of rheumatoid arthritis: 8 years of real-world observations from the rhumadata® clinical database and registry

10.1136/annrheumdis-2017-eular.2379 ◽

2017 ◽

Author(s):

D Choquette ◽

L Bessette ◽

E Alemao ◽

B Haraoui ◽

F Massicotte ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Real World ◽

Tnf Inhibitors ◽

Clinical Database ◽

Biologic Dmard

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POS0223 PATTERNS OF JANUS KINASE INHIBITOR CYCLING FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL PRACTICE: AN ANALYSIS OF THE OPAL DATASET

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2256 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 330-331

Author(s):

S. Ciciriello ◽

T. Smith ◽

C. Osullivan ◽

K. Tymms ◽

P. Youssef ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Medical Record ◽

Clinical Data ◽

Real World ◽

Visual Analytics ◽

Clinical Care ◽

Janus Kinase ◽

Second Line ◽

First Line ◽

Third Line

Background:There are currently eleven biologic and targeted synthetic (b/ts)DMARDs acting via five different modes of action available for the treatment of RA in Australia. The cost of b/tsDMARDs is subsidized by government for patients that have active RA despite six months of combination csDMARD therapy. Once a patient is eligible, the clinician can prescribe the b/tsDMARD they deem to be the most clinically appropriate for the patient. In Oct 2015 the first JAK inhibitor (JAKi) became available in Australia (tofacitinib, TOF), baricitinib (BARI) became available in Sept 2018, and upadacitinib (UPA) in May 2020. Each of these oral tsDMARDs possess different selectivity profiles towards different members of the JAK family (JAK1–3 and Tyk2).Objectives:The aim of this analysis was to determine the patterns of JAKi cycling in real-world practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record during the routine consultation1. Data from patients >18 years with RA who commenced a b/tsDMARD between Jan-2007 and Dec-2020 were included in the analysis. A visual analytics software program was used to display data on medication initiation and cessation dates, and reasons for stopping tsDMARDs, which is recorded in the medical record at the time of the decision.Results:At Dec 2020, 28% of the 52,190 patients with RA in the OPAL dataset were prescribed b/tsDMARDs. Of these patients, 3,850 (26.3%) were currently prescribed a JAKi with 51.4% receiving TOF, 29.2% BARI and 19.4% UPA. In 2020, JAKi initiations accounted for 48.8% of all initiations and 30.7% of 1st line initiations; an increase of 6.1% and 3.5% from 2019, respectively. The percentage of patients switching from a first line JAKi to a second line JAKi rather than an agent with another mode of action increased from 33.1% in 2019 to 42.6% in 2020. This is despite 26.2% in 2019 and 45.8% in 2020 of the patients switching to another JAKi citing lack of efficacy as the reason for JAKi discontinuation. In the period between May 2020, when a third JAKi (UPA) become available, and Dec 2020, the majority of patients switching from first line TOF or BARI to another JAKI switched to UPA (69.4% and 83.9%, respectively), whilst 30.6% of first line TOF patients switched to BARI (30.6%), and 16.1% of first line BARI patients switched to TOF in second line. The majority of patients switching from second line TOF or BARI to a third line JAKi switched to UPA (73% and 96%, respectively), with 27% of second line TOF patients switching to BARI and a very low number moving from second line BARI to TOF (4%). JAKi choice after a third line TOF or BARI was almost exclusively UPA (86.2% and 95.5%, respectively).Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia and JAKi cycling is increasingly common in routine clinical care. Clinical outcomes and persistence following JAKi cycling requires further investigation.References:[1]Littlejohn GO, Tymms KE, Smith T, Griffiths HT. Using big data from real-world Australian rheumatology encounters to enhance clinical care and research. Clin Exp Rheumatol. Sep-Oct 2020;38(5):874-880.Figure 1.Patterns of JAKi cycling for the management of rheumatoid arthritis in first, second and third line switching.Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platformDisclosure of Interests:Sabina Ciciriello: None declared, Tegan Smith: None declared, Catherine OSullivan: None declared, Kathleen Tymms: None declared, Peter Youssef: None declared, David Mathers: None declared, Claire Deakin: None declared, Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Geoff Littlejohn Speakers bureau: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus.

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