P200 Characterisation of remission in patients with rheumatoid arthritis treated with upadacitinib or comparators

Stephen Hall; Tsutomu Takeuchi; Glen Thomson; Paul Emery; Bernard Combe; Andrea Everding; Karel Pavelka; Yanna Song; Tim Shaw; Alan Friedman; In-Ho Song; Eduardo Mysler

doi:10.1093/rheumatology/keaa111.195

P200 Characterisation of remission in patients with rheumatoid arthritis treated with upadacitinib or comparators

Rheumatology ◽

10.1093/rheumatology/keaa111.195 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Stephen Hall ◽

Tsutomu Takeuchi ◽

Glen Thomson ◽

Paul Emery ◽

Bernard Combe ◽

...

Keyword(s):

Disease Activity ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Biologic Dmards ◽

Mixed Effect ◽

Research Grants ◽

Respective Control ◽

The Individual ◽

Support Research

Abstract Background Across all phase 3 studies, treatment with upadacitinib (UPA), a JAK1-selective inhibitor, was associated with significantly higher remission (REM) rates, compared to placebo (PBO) or active comparators, in RA patients who were methotrexate (MTX)-naive, had inadequate response to conventional synthetic (csDMARD-IR) or had inadequate response or intolerance to biologic DMARDs (bDMARD-IR). Methods REM definitions are based on composite scores of various individual assessments of disease activity. To determine the response to UPA on REM and component assessments, we assessed the proportions of patients achieving REM using multiple REM definitions, and the improvement in their respective individual components, compared to PBO or active comparators, in 3 different RA patient populations spanning a range of RA patient populations. Methods: Three phase 3 studies included patients who were MTX naïve (SELECT EARLY, n = 945), MTX-IR (SELECT COMPARE, n = 1629) and bDMARD-IR (SELECT BEYOND, n = 498). The proportion of patients achieving REM at Week 12 by 4 definitions (DAS28-CRP<2.6; CDAI <2.8; SDAI <3.3 and Boolean, defined as < 1 for TJC, SJC, patient’s global assessment of disease activity [PtGA], and CRP <1 mg/L) were determined. For each definition of REM, the mean change in each of the respective component scores was also assessed. Binary endpoints are based on Non-responder imputation (NRI), and continuous endpoints on mixed-effect model repeat measurement (MMRM). Comparisons were made between UPA-treated groups vs respective control arms (MTX, adalimumab [ADA] or PBO). Results Patient demographics and disease characteristics have been previously reported. 1-3 At 12 weeks, in EARLY and COMPARE, a significantly greater proportion of patients receiving UPA 15 mg or 30 mg QD achieved REM by all 4 definitions vs MTX, PBO or ADA (Table). In BEYOND, (a refractory population many of whom had inadequate response to multiple bDMARDs), a significantly greater proportion of patients receiving UPA 30mg achieved all REM definitions vs PBO within the first 12 weeks, with significantly greater proportions on UPA 15mg achieving DAS28-CRP<2.6 and Boolean REM. Rates of REM in BEYOND further increased through Wk 24 for both dose groups. Compared to respective control groups, patients receiving UPA 15 or 30 mg QD had significantly greater improvements in each REM disease component (except for PhGA vs ADA in COMPARE). Significantly more patients receiving UPA also achieved the required cutoffs on the individual components of Boolean REM compared to respective controls. Conclusion Significantly greater proportions of patients receiving UPA 15 or 30mg achieved REM by multiple definitions at 12 weeks compared to PBO, MTX or ADA. All disease activity components of each REM definition were significantly improved in patients receiving UPA compared to MTX or PBO, and all Boolean components were significantly improved in patients receiving UPA 15mg compared to ADA. Disclosures S. Hall: Grants/research support; AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis. T. Takeuchi: Honoraria; Mitsubishi-Tanabe Pharma Corp, Janssen Pharma KK, Chugai Pharma, Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd, BMS, Daiichi Sankyo Company Ltd, Eli Lilly Japan KK, Pfizer Japan Inc. Grants/research support; Pfizer Japan Inc., Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corp, Nippon Kayaku Co., Ltd, Taisho Toyama Pharma, Takeda Pharma, AYUMI Pharma, Takahashi Industrial. G. Thomson: Consultancies; Amgen. Grants/research support; AbbVie. P. Emery: Grants/research support; Research grants and consulting fees from Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. B. Combe: Grants/research support; Consultancy fees from Abbvie, BMS, Jansen, Lilly, MSD, Pfizer, Roche Chugai, UCB. A. Everding: None. K. Pavelka: Honoraria; Honoraria for lectures and consultations from companies: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie. Y. Song: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. I. Song: Corporate appointments; Employee of AbbVie. E. Mysler: Grants/research support; Research grants and consulting fees from AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz.

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SAT0151 EFFICACY AND SAFETY OF UPADACITINIB VERSUS ABATACEPT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE OR INTOLERANCE TO BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-CHOICE): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2059 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1015-1016

Author(s):

A. Rubbert-Roth ◽

J. Enejosa ◽

A. Pangan ◽

R. Xavier ◽

B. Haraoui ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Study Drug ◽

Signs And Symptoms ◽

Drug Discontinuation ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Double Blind ◽

Biologic Dmards

Background:Upadacitinib (UPA) is an oral, reversible, selective JAK 1 inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA). The efficacy/safety of UPA has been demonstrated in phase 3 studies, including superiority to adalimumab in patients (pts) with prior inadequate response (IR) to methotrexate.1-4Objectives:To assess the efficacy/safety of UPA vs abatacept (ABA) in pts with prior IR or intolerance to biologic DMARDs (bDMARDs).Methods:Pts were randomized to once daily UPA 15 mg or intravenous ABA (at Day 1, Weeks [Wks] 2, 4, 8, 12, 16 and 20 [< 60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg]), with all pts continuing background stable csDMARDs. The study was double-blind for 24 wks. Starting at Wk 12, pts who did not achieve ≥20% improvement from baseline (BL) in both tender and swollen joint counts at two consecutive visits, had background medication(s) adjusted or initiated. The primary endpoint was change from BL in DAS28(CRP) at Wk 12 (non-inferiority). The non-inferiority of UPA vs ABA was tested using the 95% CI of treatment difference against a non-inferiority margin of 0.6. The two key secondary endpoints at Wk 12 were change from BL in DAS28(CRP) and the proportion of pts achieving clinical remission (CR) based on DAS28(CRP), defined as DAS28(CRP) <2.6. Both endpoints were to demonstrate the superiority of UPA vs. ABA. Treatment-emergent adverse events (TEAEs) are reported up to Wk 24 for all pts who received at least one dose of study drug.Results:Of 612 pts treated; 67% of pts had received 1 prior bDMARD, 22% received 2 prior bDMARDs, and 10% received ≥ 3 prior bDMARDs. 549 (90%) completed 24 wks of treatment. Common reasons for study drug discontinuation were AEs (UPA, 3.6%; ABA, 2.6%) and withdrawal of consent (UPA, 1.7%; ABA, 2.6%).Non-inferiority and superiority were met for UPA vs ABA at Wk 12 for change from BL in DAS28(CRP) (-2.52 vs -2.00; -0.52 [-0.69, -0.35]; p <0.001 for UPA vs ABA). UPA also demonstrated superiority to ABA in achieving DAS28(CRP) <2.6 (30.0% vs 13.3%; p <0.001 for UPA vs ABA; Figure 1). Improvements in disease activity and remission rates were maintained through Wk 24. The proportions of pts achieving low disease activity (defined as DAS28(CRP) ≤3.2), ACR20, ACR50, and ACR70 responses were greater with UPA compared with ABA at Wk 12 (nominal p <0.05). More stringent outcome measures – CR, ACR50, and ACR70 responses - remained higher with UPA than ABA through Wk 24 (nominal p <0.05). Incidence of serious TEAEs, AEs leading to discontinuation, hepatic disorders, and CPK elevations were numerically higher with UPA versus ABA (Figure 2). Eight cases of herpes zoster were reported (4 in each treatment arm). No malignancies were reported. One case of adjudicated MACE, two adjudicated cases of VTE (1 pt with DVT and 1 pt with PE; both pts had at least one risk factor for VTE), and one treatment-emergent death were reported with UPA.Conclusion:In RA pts with a prior IR or intolerance to bDMARDs, UPA demonstrated superior improvement in signs and symptoms vs ABA based on change in DAS28(CRP) and in achieving CR at Wk 12. The safety profile of UPA was consistent with the phase 3 RA studies with no new risks identified.References:[1]Burmester GR, et al. Lancet. 2018;391(10139):2503-12[2]Fleischmann R, et al. Arthritis Rheumatol. 2019;71(11):1788-800[3]Genovese MC, et al. Lancet. 2018;391(10139):2513-24[4]Smolen JS, et al. Lancet. 2019;393(10188):2303-11Disclosure of Interests:Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, 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, Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Nasser Khan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ying Zhang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Naomi Martin Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

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P209 Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the select Phase 3 clinical programme

Rheumatology ◽

10.1093/rheumatology/keaa111.204 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Stanley B Cohen ◽

Ronald van Vollenhoven ◽

Kevin Winthrop ◽

Cristiano Zerbini ◽

Yoshiya Tanaka ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Safety Profile ◽

Clinical Signs ◽

Integrated Analysis ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Research Grants ◽

Treatment Groups ◽

All Treatment

Abstract Background Upadacitinib (UPA), a JAK1-selective inhibitor, significantly improved clinical signs and symptoms of rheumatoid arthritis (RA) in patients naïve to methotrexate (MTX) and with an inadequate response to conventional synthetic DMARDs (csDMARD-IR) or biologic DMARDs (bDMARD-IR). The objective was to assess the safety of UPA as monotherapy (mono) and as combination therapy with background csDMARDs in patients with moderately to severely active RA from the safety database of the Phase 3 clinical programme. Methods Treatment-emergent adverse events (TEAEs) from 5 pivotal, randomised, double-blind, controlled Phase 3 trials of UPA 15 mg or 30 mg QD in RA patients were analysed using integrated short-term (ST), individual studies with long-term (LT) active comparator and integrated LT (all Phase 3 exposure; E/100PY) analyses sets. Results Across the Phase 3 trials, 3834 patients received ∼1 dose of UPA 15 mg (n = 2630) or 30 mg QD (n = 1204) »4020.1 PY of UPA exposure with no option to switch doses. The ST frequencies of overall SAEs and AEs leading to discontinuation were low, but higher on both UPA doses vs PBO. LT event rates were similar on UPA 15 mg vs ADA and slightly higher on UPA vs MTX mono. Deaths occurred in all treatment groups. Serious infection (SIEs) frequencies were higher on both UPA doses vs PBO. SIE rates on both UPA doses were higher vs MTX, but similar on UPA 15 mg vs ADA. Herpes zoster (HZ) frequencies and rates were higher on both UPA doses vs PBO, and vs MTX, ADA, respectively. The rates of SIE and HZ were higher on UPA 30 vs 15 mg. Adjudicated MACE were reported in all treatment groups including PBO. LT MACE rates were similar on UPA 15 mg and ADA and on UPA 15 mg and MTX mono, but higher on UPA 30 mg mono (low number of events, 2-4 per set). Adjudicated VTEs occurred at comparable frequencies on UPA vs PBO and at comparable rates on UPA vs active comparators. Malignancy (excluding non-melanoma skin cancer [NMSC]) rates were similar on UPA vs MTX, UPA 15 mg vs ADA, and 15 vs 30 mg. The NMSC rates on UPA 15 mg and ADA were similar; the rate on 30 mg was higher than 15 mg, but both UPA NMSC rates were in the range reported for RA patients treated with DMARDS. The standardised incidence ratio (95% CI) for malignancy (15 mg: 0.98 [0.61, 1.49], 30 mg: 1.49 [0.85, 2.42]) was not elevated vs the general population. Conclusion Treatment with UPA increased the risk of SIE and HZ, but not those of VTE, MACE, and malignancy vs comparators. These data support that UPA has an acceptable safety profile in the treatment of moderately to severely active RA. Disclosures S.B. Cohen: Grants/research support; Received grants and personal fees from Amgen, Abbvie, Boehringer Ingelheim, Pfizer and Sandoz. R. van Vollenhoven: Consultancies; AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Grants/research support; Received grants from AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Lilly, Pfizer, and UCB. K. Winthrop: Consultancies; Received consulting fees and research grants from UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, and Roche. C. Zerbini: Consultancies; Merck, Pfizer, Sanofi-Aventis and Pfizer. Grants/research support; Received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche. Y. Tanaka: Honoraria; Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, Pfizer, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi-kasei. Grants/research support; Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama. L. Bessette: Grants/research support; Speaking fees, consulting fees, and research grants from Amgen, BMS, Janssen, Roche, UCB Pharma, AbbVie Inc, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, and Novartis. Y. Zhang: Corporate appointments; Employee of AbbVie. N. Khan: Corporate appointments; Employee of AbbVie. B. Hendrickson: Corporate appointments; Employee of AbbVie. J.V. Enejosa: Corporate appointments; Employee of AbbVie. G. Burmester: Honoraria; Received speaking or consulting fees from AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma.

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P225 Inhibition of structural joint damage with upadacitinib as monotherapy or in combination with MTX in patrients with RA: one-year outcomes from the select Phase 3 programme

Rheumatology ◽

10.1093/rheumatology/keaa111.220 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Charles Peterfy ◽

Mark C Genovese ◽

In-Ho Song ◽

Alan Friedman ◽

Stephen Hall ◽

...

Keyword(s):

Radiographic Progression ◽

Joint Damage ◽

Significant Inhibition ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Missing Data Imputation ◽

Research Grants ◽

Structural Joint ◽

Change In Mean

Abstract Background Long-term prevention of structural joint damage is a key treatment goal in the management of RA. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients and in combination with MTX in patients with inadequate response (IR) to MTX. Objectives: To evaluate the progression of structural joint damage (radiographic) through Week 48 in patients with moderately to severely active RA treated with UPA monotherapy or in combination with MTX. Methods Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs). MTX-naïve patients were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N = 945], while MTX-IR patients were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT-COMPARE, N = 1629]. Both RCTs specifically enrolled patients at high risk for progression of joint damage (high disease activity including elevated hsCRP, presence of baseline erosions and ACPA and/or RF positivity). The mean changes (D) from baseline (BL) in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) as well as the proportion of patients with no radiographic progression (ΔmTSS ≤0) at Weeks 24/26 and 48 were determined in both RCTs. Data were analyzed by linear extrapolation (LE) for missing data imputation and treatment switching, and as observed (AO). Results BL demographics have been reported previously. At Weeks 24/26, UPA as monotherapy and in combination with background MTX significantly inhibited radiographic progression measured by mean DmTSS and the proportion of patients with no radiographic progression vs MTX and PBO, respectively. The significant inhibition of radiographic progression with UPA was maintained through Week 48 vs MTX (LE and AO) in EARLY and vs PBO (LE) in COMPARE. Following the switch of all PBO patients to UPA in COMPARE by Week 26, no further change in mean mTSS was observed through Week 48. The inhibition of radiographic progression vs comparators was not only observed for the overall mTSS scores but also its components - the JSN and ES in both RCTs (LE and AO). Conclusion UPA both as monotherapy, and in combination with background MTX, was effective in inhibiting the progression of structural joint damage through Week 48 in MTX-naïve, and MTX-IR patients, respectively. Disclosures C. Peterfy: Consultancies; AbbVie, Acerta, Amgen, AstraZeneca, Bristol-Myers Squibb, Centrexion, Daiichi Sankyu, Five Prime Therapeutics, Genentech, Hoffmann-La Roche, Janssen, Lilly USA, MedImmune, Merck, Novartis, Plexxikon, Pfizer, Sanofi, Salix-Santarus, Samsung. M.C. Genovese: Consultancies; Consultant for and has received grants from AbbVie Inc, Lilly, Pfizer, Galapagos, and Gilead. I. Song: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. S. Hall: Consultancies; Received research grants and consultancy fees from AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis. E. Mysler: Grants/research support; Received research grants and speaker’s bureau fees from Bristol-Myers Squibb, Roche, Eli Lilly, AbbVie, Novartis, Janssen, and Pfizer. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Samsung, Pfizer, UCB, Mundipharma, Hospira, and Eli Lilly. X. Baraliakos: Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB. J. Enejosa: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. Y. Li: Corporate appointments; Employee of AbbVie. S. Chen: Corporate appointments; Employee of AbbVie. V. Strand: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Celgene, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB.

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POS0638 DISEASE SEVERITY AND OUTCOMES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS WHO RECEIVE A NEWLY APPROVED BIOLOGIC: REAL-WORLD US EXPERIENCE WITH SARILUMAB FROM THE ACR RISE REGISTRY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3655 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 556.3-557

Author(s):

S. Fiore ◽

L. Chen ◽

C. Clinton ◽

H. Yun ◽

A. Praestgaard ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Severity ◽

Real World ◽

Tnf Inhibitors ◽

Categorical Variables ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Research Grants ◽

Fda Approval

Background:Patients with rheumatoid arthritis (RA) who have received multiple biologics or targeted therapies over time tend to have more refractory and more severe disease, which may lead to worse clinical response to treatment.Objectives:We used data from the ACR RISE registry to assess whether disease severity was greater in those who received sarilumab shortly after its FDA approval (May 2017) than in subsequent time periods and to evaluate the effectiveness of sarilumab in populations with various degrees of disease severity.Methods:Patients with RA who initiated sarilumab treatment in the period 2017-2020 were identified in the ACR RISE registry and divided into Cohort 1 (2017, year of the FDA approval) and the calendar year-based Cohorts 2-4 (2018-2020). Patient demographics, RA-related features, and comorbidities were determined using data prior to sarilumab initiation. The cohorts were compared using chi-square test (categorical variables) and a nonparametric test (continuous variables). Sarilumab effectiveness was assessed using 3 cohorts assembled based on progressively restrictive criteria: Active Disease cohort (Clinical Disease Activity Index [CDAI] >10 or Routine Assessment of Patient Index Data 3 [RAPID3] >6, and C-reactive protein, if measured, ≥8 mg/L), TARGET Eligibility cohort (patients who satisfied enrolment criteria for TARGET,1 a Phase 3 sarilumab trial in patients with RA and an inadequate response to TNF inhibitors), and TARGET Baseline cohort (patients from TARGET Eligibility cohort with characteristics weighted to match those from the TARGET trial baseline,1 using the matching-adjusted indirect comparison method2). In all 3 effectiveness cohorts, mean changes in CDAI and RAPID3 at 6 and 12 months post-initiation of sarilumab were evaluated using a model adjusted for baseline score, age, sex, race, calendar year, and seropositivity.Results:A total of 2949 patients, treated by 585 rheumatologists, initiated sarilumab treatment in the period 2017–2020. The 4 yearly cohorts were relatively similar in terms of patients’ age, sex, race, and most clinical characteristics. However, patients receiving sarilumab shortly after FDA approval (Cohort 1) had more ambulatory visits, a greater number of previously used non-TNFi biologics (particularly tocilizumab), and a higher comorbidity burden, and were more likely to be current users of glucocorticoids or opioids than sarilumab initiators in the subsequent 3 years. In the 3 cohorts used to assess sarilumab effectiveness, the greatest improvement was observed in the TARGET Baseline cohort, which also had the greatest mean baseline CDAI score (43), compared with the other two (24 both).Conclusion:In this real-world cohort, we observed modest evidence for channeling of patients with greater RA severity and greater prior exposure to non-TNFi biologics to sarilumab shortly after its FDA approval. This cohort effect did not diminish the effectiveness of sarilumab. All cohorts showed improvement, with the greatest clinical improvement observed in the cohort with the highest baseline CDAI score who most closely resembled those enrolled in a phase 3 trial of patients with an inadequate response to TNF inhibitors.References:[1]Fleischmann R, et al. Arthritis Rheumatol 2017;69:277-290.[2]Signorovitch JE et al. Value Health 2012;15:940-7.Figure 1.Adjusted improvements in CDAI and RAPID3Acknowledgements:This study was sponsored by Sanofi. Medical writing support was provided by Vojislav Pejović, PhD (Eloquent Medical Affairs, division of Envision Pharma Group) and funded by Sanofi.Disclosure of Interests:Stefano Fiore Employee of: Sanofi, Lang Chen: None declared, Cassie Clinton Consultant of: Information available in profile, Huifeng Yun Grant/research support from: Research support for Pfizer, Amy Praestgaard Employee of: Sanofi, Kerri Ford Employee of: Sanofi, Jeffrey Curtis Consultant of: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB, Grant/research support from: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB

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FRI0140 IMPACT OF BASELINE DEMOGRAPHICS AND DISEASE ACTIVITY ON OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.907 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 653-654

Author(s):

M. Weinblatt ◽

E. Mysler ◽

A. Ostor ◽

A. Broadwell ◽

S. Jeka ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Herpes Zoster ◽

Disease Activity ◽

Integrated Analysis ◽

Inadequate Response ◽

Research Support ◽

Phase 3 ◽

Double Blind ◽

Asian Region ◽

Disease Characteristics

Background:Upadacitinib (UPA), an oral selective JAK1 inhibitor, has demonstrated favorable efficacy and acceptable safety in five Phase 3 global studies in patients with moderately to severely active rheumatoid arthritis (RA).1–5Objectives:This analysis reports the efficacy and safety of UPA in predefined RA patient subgroups based on differences in baseline demographics and disease activity.Methods:Data were pooled from three pivotal, double-blind, PBO-controlled, multicenter, Phase 3 studies in patients with RA who had an inadequate response(IR) to conventional synthetic DMARDs (csDMARD-IR: SELECT-NEXT [N=661]), MTX(MTX-IR; SELECT-COMPARE[N=1629]), or biologic DMARDs(bDMARD-IR: SELECT-BEYOND[N=498]). Two integrated analysis sets were evaluated: one comparing UPA 15 mg QD vs PBO(SELECT-NEXT, SELECT-COMPARE, SELECT-BEYOND) and the other comparing UPA 15 mg QD and UPA 30 mg QD vs PBO(SELECT-NEXT, SELECT-BEYOND). All patients received background treatment with csDMARDs. The proportion of patients achieving ACR20 and DAS28(CRP) ≤3.2 at Week 12 was evaluated by predefined baseline demographics and disease activity measure groups, including age, sex, weight, BMI, race, geographic region, duration of RA, RF, and ACPA status, and level of high sensitivity CRP. Non-responder imputation was used for missing data. Subgroup analyses for safety were performed for age, race, sex, weight, BMI, and Asian region.Results:Across the three Phase 3 studies, 1036, 384, and 1041 patients received UPA 15 mg QD, UPA 30 mg QD or PBO, respectively. The demographic and baseline disease characteristics in the two integrated analysis sets were balanced across treatment groups. ACR20 and DAS28 ≤3.2 response rates at Week 12 were consistently higher with UPA 15 mg and UPA 30 mg vs PBO across the evaluated demographic and baseline disease characteristics(Figure 1a,Figure 1b). The efficacy of UPA 15 mg QD was generally similar to that observed with UPA 30 mg QD. At 12 weeks, the proportion of patients with treatment-emergent AEs, serious AEs, severe AEs, and AEs leading to discontinuation were generally comparable across different age, sex, race, weight, and BMI groups. Compared with the global population, patients receiving UPA in the Asian region had a higher rate of CPK elevations(UPA 30 mg only) and herpes zoster; herpes zoster also has been observed to be higher in the Asian region with other JAK inhibitors.6,7Conclusion:In this analysis of pooled integrated efficacy data in csDMARD-IR or bDMARD-IR patients with RA, UPA 15 mg or 30 mg QD in combination with csDMARDs improved efficacy outcomes at Week 12 when compared with PBO across all predefined subgroups evaluated.References:[1]Burmester GR, et al. Lancet 2018 23;391:2503–2512;[2]Genovese MC, et al. Lancet 2018; 391:2513–24;[3]Smolen JS, et al. Lancet 2019 May 23[Epub ahead of print];[4]van Vollenhoven R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 891;[5]Fleischmann R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 890;[6]Winthrop KL, et al. Arthritis Rheum 2014;66:2675-84;[7] Winthrop KL, et al. ACR 2016 [Abstract 3027]Disclosure of Interests:Michael Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, Lily, Sanofi/Regeneron, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, Gilead, Horizon, Lily, Pfizer, Roche, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Aaron Broadwell Grant/research support from: Janssen Research & Development, LLC, Janssen, Eli Lilly, Consultant of: AbbVie, Amgen, AstraZeneca, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Speakers bureau: AbbVie, Amgen, Celgene, GSK, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi-Regeneron, UCB, Sławomir Jeka Grant/research support from: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Kendall Dunlap Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sheng Zhong Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Katya Cherny Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Grace Wright Consultant of: AbbVie, Amgen, BMS, Exagen, Janssen, Lilly, Medac, Myriad Autoimmune, Novartis, Pfizer, Sanofi Genzyme Regeneron, and UCB, Speakers bureau: AbbVie, Amgen, BMS, Exagen, Lilly, Medical Education Resource, Myriad Autoimmune, Novartis, Sanofi Genzyme Regeneron, UCB, and Vindico

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FRI0095 SARILUMAB IMPROVED PATIENT-PERCEIVED IMPACT OF RHEUMATOID ARTHRITIS WHATEVER THE BASELINE DISEASE ACTIVITY: FIRST RESULTS FROM AN INTERVENTIONAL NON CONTROLLED STUDY: SARIPRO, IN MODERATE AND SEVERE RHEUMATOID ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5518 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 626.2-626

Author(s):

L. Gossec ◽

R. M. Flipo ◽

T. Schaeverbeke ◽

C. Albert ◽

A. Baillet ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Primary Endpoint ◽

Daily Practice ◽

Controlled Study ◽

Inadequate Response ◽

Interventional Study ◽

Research Support ◽

Biologic Dmards ◽

Patient Reported

Background:Sarilumab, an anti-IL-6R antibody, is approved for the treatment of moderate to severe RA and shown efficacy on disease activity and patient-reported outcomes (PROs). Detailed analyses of drug efficacy from the patient point of view is important. SariPRO is a pragmatic interventional study close to the daily practice.Objectives:To assess the effectiveness of sarilumab on several PROs using the RAID (Rheumatoid Arthritis Impact of Disease) score.Methods:The SariPRO study (NCT 03449758) was a French multicenter interventional study assessing the effects of sarilumab 200 mg on PROs in patients with moderately to severely active RA with an inadequate response or intolerance to conventional synthetic or biologic DMARDs. The primary endpoint was change in total RAID score from baseline to week 24 (RAID ranges 0-10 where 10 is maximal impact). Changes from baseline for RAID, DAS28-ESR and CDAI according to baseline disease activity were analyzed as secondary outcomes. Safety was assessed by monitoring adverse events (AE). All statistical analyses were descriptive, 95% CI was given when appropriate.Results:84 patients were included in 31 centers and 62 were evaluable and analyzed for effectiveness. They had similar characteristics to the 84 patients at baseline and were as expected for an RA population initiating a biologic: mean (SD) age: 59.9 (12.4) years, 71.0% female, disease duration 9.7 (10.3) years, rheumatoid factor positivity 82.5%, ACPA positivity 86.4%, and DAS28=4.9 (11). Total RAID score decreased significantly from 5.7 (2.0) at baseline to 3.3 (2.5) at W24; mean change was -2.4 [95% CI: -3.0; -1.8]. Furthermore, this improvement was noted both for highly and less active patients at baseline: for patients with DAS28-ESR < 5.1 (n=31), mean change was -1.56 [-2.28; -0.83] and for patients with DAS28-ESR≥5.1 (n=27), mean change was -1.98 [-2.91; -1.05]. Changes in DAS28-ESR and CDAI were significant (-2.8 [-3.2; -2.4] and -15.2 [-18.5; -11.8], respectively). AEs were consistent with the safety profile of anti-IL-6R antibodies and with results from RCTs (data not shown).Conclusion:In this real world study, treatment with sarilumab during 24 weeks in RA patients led to an improvement in the total RAID score irrespective of baseline levels of disease activity. This is the first time RAID score is used as the primary endpoint in a study.References:[1]Study was sponsored by Sanofi GenzymeDisclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi, Thierry Schaeverbeke: None declared, Christine Albert: None declared, Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, marie-Christophe Boissier: None declared, Cyrille Confavreux: None declared, Gregoire CORMIER: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Elisabeth Gervais Solau: None declared, Sophie Godot: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Slim Lassoued: None declared, Thierry Lequerre: None declared, Frederic Lioté Consultant of: CME: Nordic Pharma, Christian Marcelli: None declared, Yves Maugars: None declared, Minh Nguyen: None declared, Aleth Perdriger: None declared, Yves-Marie Pers: None declared, Edouard Pertuiset: None declared, Lucile Poiroux: None declared, Carole Rosenberg: None declared, Christian Roux: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Martin SOUBRIER: None declared, Pascale Vergne-Salle: None declared, Charles Zarnitsky: None declared, Eric Fakra Consultant of: Janssen, Lundbeck, Otsuka, Sanofi, Hubert MAROTTE Grant/research support from: Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Consultant of: AbbVie, Amgen, Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Paid instructor for: Sanofi-Aventis, Speakers bureau: Sanofi-Aventis, Florence E Lévy-Weil Employee of: Sanofi Genzyme employee

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P128 A subgroup analysis of the efficacy of filgotinib for patients with moderately active RA following an inadequate response to methotrexate

Rheumatology ◽

10.1093/rheumatology/keab247.123 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Maya H Buch ◽

David Walker ◽

Patrick D W Kiely ◽

Christopher J Edwards ◽

Jane Barry ◽

...

Keyword(s):

Disease Activity ◽

Short Form ◽

Health Assessment ◽

Physical Component Score ◽

Inadequate Response ◽

Research Support ◽

Reactive Protein ◽

American College Of Rheumatology ◽

Moderate Disease ◽

Sf 36

Abstract Background/Aims Filgotinib is an oral, preferential janus kinase 1 inhibitor. FINCH 1 (NCT02889796) was a phase III, double-blind, placebo- and active-controlled study evaluating filgotinib efficacy and safety in patients with rheumatoid arthritis (RA) after inadequate response to methotrexate (MTX; MTX-IR). Methods MTX-IR patients with moderately or severely active RA were randomised (3:3:2:3) to filgotinib 200 mg daily, filgotinib 100 mg daily, adalimumab 40 mg every 2 weeks, or placebo on a background of stable MTX for up to 52 weeks. An exploratory subgroup analysis of FINCH 1 was conducted in patients with moderately active RA based on Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP])>3.2-≤5.1 at baseline. Proportion of patients achieving 20%/50%/70% improvement from baseline in American College of Rheumatology core criteria (ACR20/50/70), DAS28(CRP)≤3.2, DAS28(CRP)<2.6, change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Physical Component Score (SF-36 PCS), patient-reported pain, and modified total Sharp/van der Heijde score (mTSS) were assessed at week (W)12 and W24. All analyses were exploratory without multiplicity adjustment; nominal P-values are reported. Results Of 1,755 treated patients, 24% had moderate disease at baseline with similar proportions (21.9%-26.9%) across treatment groups. In each treatment arm, baseline characteristics were well balanced for the moderate disease activity subpopulation. The majority (77%) were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.7) years; mean (SD) baseline DAS28(CRP) was 4.6 (0.42). At W12 and W24, proportions achieving ACR20/50/70, DAS28(CRP)<2.6, and DAS28(CRP)≤3.2 were significantly higher for both filgotinib doses relative to placebo (Table). Improvement in HAQ-DI was significantly greater vs placebo at W12 but not W24 for both filgotinib doses (Table 1). For both doses of filgotinib vs placebo, SF-36 PCS and pain were significantly improved and there was numerically less radiographic progression as assessed by mTSS at W12 and W24 (Table). Composite disease activity, HAQ-DI, and mTSS scores with both filgotinib doses were comparable to adalimumab. P128 Table 1:Efficacy outcomes at week 12 and week 24Week 12Week 24FIL 200 mg (n = 104)FIL 100 mg (n = 121)ADA (n = 72)PBO (n = 128)FIL 200 mg (n = 104)FIL 100 mg (n = 121)ADA (n = 72)PBO (n = 128)ACR2077.9***67.8***65.343.872.1**75.2***68.154.7ACR5043.3***37.2***41.716.452.9***47.1**56.930.5ACR7019.2***17.4***15.33.932.7***29.8**29.213.3DAS28 (CRP)<2.647.1***37.2***44.415.661.5***46.3***50.023.4DAS28 (CRP)≤3.267.3***63.6***66.739.174.0***73.6***62.549.2ΔHAQ-DI−0.51a,***−0.40b,*−0.47c−0.28d−0.57e−0.53f−0.65g−0.48hΔmTSS0.02i0.06j0.03k0.16l−0.04m,*0.11n−0.01o0.21pΔSF-36 PCS7.8q,***6.4r,***7.0s3.7t8.8u,**7.2v,*9.5w5.8xΔPain, mm−24***−23***−23−12−28***−28***−28−21***P<0.001 vs PBO;**P<0.01 vs PBO;*P<0.05 vs PBO; all P-values are nominal. Binary efficacy endpoints were compared between FIL and PBO using Fisher's exact test. Comparisons of change from baseline between FIL vs PBO were conducted using mixed-effects models for repeated measures including treatment group, visit, treatment group by visit, baseline value as fixed effects, and subjects as random effect.an = 98;bn = 114;cn = 67;dn = 117;en = 89;fn = 108;gn = 61;hn = 100;in = 94;jn = 113;kn = 62;ln = 112;mn = 89;nn = 105;on = 60;pn = 97;qn = 99;rn = 116;sn = 67;tn = 118;un = 91;vn = 109;wn = 62;xn = 100.ΔHAQ-DI, change from baseline in Health Assessment Questionnaire-Disability Index; ΔmTSS, change from baseline in modified total Sharp/van der Heijde score; ΔSF-36 PCS, change from baseline in Short Form-36 Physical Component Score; ACR, American College of Rheumatology; ADA, adalimumab; DAS28(CRP), Disease Activity Score in 28 joints with C-reactive protein; FIL, filgotinib; PBO, placebo. Conclusion In a subgroup of patients from FINCH 1 with baseline moderately active RA, significantly greater improvements in disease activity were observed with both filgotinib doses over placebo and associated with lower radiographic progression and reduced functional deficit. Disclosure M.H. Buch: Consultancies; MHB reports serving as a consultant for AbbVie; Eli Lilly; Gilead Sciences, Inc.; Sandoz; Sanofi; and Serono. Grants/research support; MHB reports grants or research support from Pfizer, Roche, and UCB. D. Walker: Grants/research support; DW has received funding from Bristol-Myers Squibb; Eli Lilly; Gilead Sciences, Inc.; Novartis; and Pfizer, Inc. P.D.W. Kiely: Other; PK has attended advisory boards, been part of a speakers bureau, or received support to attend educational meetings from AbbVie, Gilead, Lilly, Novartis, and Sanofi. C.J. Edwards: Consultancies; CJE has provided consultancy for AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. Member of speakers’ bureau; CJE has served on speaker's bureaus for AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. Grants/research support; CJE reports grants from AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. J. Barry: Corporate appointments; JB is an employee of Gilead Sciences Ltd. G. McCaughey: Corporate appointments; GMcC is an employee of Gilead Sciences Ltd. L. Akroyd: Corporate appointments; LA is an employee of Gilead Sciences Ltd. I. Tiamiyu: Corporate appointments; IT is an employee of Gilead Sciences, Inc. L. Ye: Corporate appointments; LY is an employee of Gilead Sciences, Inc. K. Chen: Corporate appointments; KC is an employee of Gilead Sciences, Inc. P.C. Taylor: Consultancies; PCT has served as a consultant to AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, BMS, Roche, Sanofi, Nordic Pharma, Fresenius, and UCB. Grants/research support; PCT reports research grants from Gilead Sciences, Inc.; Galapagos, and Celgene.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1233 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 327.1-328

Author(s):

A. Kavanaugh ◽

M. H. Buch ◽

B. Combe ◽

L. Bessette ◽

I. H. Song ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Inadequate Response ◽

Research Support ◽

Two Phase ◽

First Occurrence ◽

Activity Measures ◽

Disease Activity Measures

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

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