scholarly journals 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

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

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

Rheumatology ◽  
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.

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

Rheumatology ◽  
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.

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

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

scholarly journals 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 ◽  
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.

scholarly journals FRI0357 IMPROVED PAIN AND FATIGUE WITH IXEKIZUMAB TREATMENT IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND PREVIOUS INADEQUATE RESPONSE TO TNF INHIBITORS: THREE YEAR FOLLOW-UP FROM A PHASE 3 STUDY (SPIRIT-P2)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 775.1-775
Author(s):  
A. M. Orbai ◽  
K. De Vlam ◽  
P. Nash ◽  
J. Birt ◽  
G. Gallo ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Joint Pain ◽  
Categorical Variables ◽  
Inadequate Response ◽  
Research Support ◽  
Phase 3 ◽  
Meaningful Improvement ◽  
Sf 36 ◽  
Patient Reported ◽  
Pharmaceutical Industries

Background:Psoriatic arthritis (PsA) is a chronic and complex inflammatory disease with both articular and extra-articular symptoms. Pain and fatigue are two of the most common patient-reported symptoms. Improvements in pain and fatigue have been demonstrated with up to 2 years of treatment with ixekizumab (IXE) in patients who had an inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi).1,2Objectives:To report improvements in pain and fatigue in TNFi-experienced patients with PsA who were treated with IXE for 3 years (156 weeks).Methods:SPIRIT-P2 (NCT02349295) was a 156-week, Phase 3 study that included patients who met the Classification Criteria for Psoriatic Arthritis (CASPAR) and had an inadequate response or intolerance to 1 or 2 TNFi. Although there was a placebo group through Week 24, these data were derived only from patients in the intent-to-treat population randomized to IXE at baseline. After a 160-mg starting dose, patients received 80 mg subcutaneous IXE every 2 or 4 weeks (Q2W or Q4W). Patients self-rated their symptoms using the Joint Pain Visual Analog Scale (Joint Pain VAS; 0 [none] to 100 [worst imaginable]), the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; with the domains ranging from 0 [worst] to 100 [best]), and the Fatigue Severity Numeric Rating Scale (Fatigue NRS; 0 [none] to 10 [worst imaginable]). Minimum clinically important difference (MCID) cutoffs were ≥10 for Joint Pain VAS, ≥5 for SF-36 domains, and ≥3 for Fatigue NRS. Missing values were imputed by modified baseline observation carried forward for continuous variables and modified non-responder imputation for categorical variables.Results:The proportions of patients who completed Week 156 were 70/122 (57.4%) in the IXE Q4W group and 55/123 (44.7%) in the IXE Q2W group. At Week 156, mean change from baseline for the Joint Pain VAS was -28.9 (IXE Q4W) and -25.3 (IXE Q2W) (Fig. A). In addition, 51.8% of patients on IXE reported clinically meaningful improvement of joint pain (56.1% IXE Q4W, 47.5% IXE Q2W) at Week 156. Patients reported an 18-point mean improvement in the SF-36 bodily pain domain at Week 156 (Fig. B). Patients also reported improvements in fatigue up to Week 156 (Fig. C), with 35.0% of patients achieving the MCID on the Fatigue NRS (39.4% IXE Q4W, 30.6% IXE Q2W). Improvement in fatigue was supported by a14-point mean improvement in the vitality domain of the SF-36 at Week 156 (Fig. D).Conclusion:In patients with PsA who had an inadequate response or intolerance to TNFi, improvements in pain and fatigue were sustained through 3 years of IXE treatment in both the Q2W and Q4W treatment groups.References:[1]Kavanaugh A, Marzo-Ortega H, Vender R, et al.Clin Exp Rheumatol. 2019;37(4):566-574.[2]Turkiewicz A, Gellett A, Kerr L, et al. [abstract]Arthritis Rheumatol. 2018;70(S9):2577.Disclosure of Interests:Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Kurt de Vlam Grant/research support from: Celgene, Consultant of: Celgene, Eli Lilly and Company, UCB, Novartis, and Pfizer, Speakers bureau: Celgene, Eli Lilly and Company, UCB, Novartis, and Pfizer, 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, Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Keri Stenger Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Vladimir Geneus Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, 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

scholarly journals O32 Serious infection with tocilizumab compared to TNF-inhibitors and other bDMARDS in rheumatoid arthritis patients: does line of therapy matter?

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Kim Lauper ◽  
Lianne Kearsley-Fleet ◽  
Rebecca Davies ◽  
Kath Watson ◽  
Mark Lunt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Real World ◽  
Disease Duration ◽  
Tnf Inhibitors ◽  
World Population ◽  
Research Support ◽  
Serious Infection ◽  
Number Of Patients ◽  
Serious Infections ◽  
Line Of Therapy

Abstract Background/Aims  In the real-world, tocilizumab is prescribed to a population of patients different from those prescribed TNF-inhibitors, often older with longer disease duration, worse functional status and more previous b- or tsDMARDs. The aim of this study was to evaluate if and how the risk of serious infection on tocilizumab and other bDMARDs differs when stratifying by line of therapy in a real-world population of rheumatoid arthritis patients. Methods  We included patients registered in the BSRBR-RA treated with tocilizumab, etanercept, adalimumab, infliximab, certolizumab, abatacept or rituximab, including biosimilars. Primary outcome was the occurrence of a serious infection (defined as infection requiring hospitalisation, intravenous antibiotics or resulting in death). Primary covariate of interest was line of therapy (from first to fifth line of therapy). Every change to another b- or tsDMARD was considered a new line of therapy, but not a change between a bio-original and a biosimilar. Hazard ratios (HR) of serious infections were estimated using an inverse probability weighted Cox regression, based on a propensity score including baseline patient and disease characteristics, and adjusting for time in study (see table). The reference group was etanercept, which included the highest number of patients. Treatment exposure was analysed without and with stratification by line of therapy. Results  A total of 33,916 treatment courses were included (Table) contributing to 62,532 years of follow-up. Compared to etanercept, participants starting abatacept, tocilizumab and rituximab were older, had more previous bDMARDs, longer disease duration and more comorbidities. The crude HR of serious infections were higher with infliximab and adalimumab, lower with certolizumab and rituximab, and not significantly different for abatacept and tocilizumab compared to etanercept. After adjustment, HR of serious infections were higher with tocilizumab, adalimumab and infliximab. However, when stratified by line of therapy, HR were no longer significantly different compared to etanercept for tocilizumab, adalimumab and infliximab for most lines of therapy. Conclusion  Whilst initially there appears to be a difference in rates of serious infections between biologic therapies, line of therapy may be a confounding factor when comparing the risk of serious infections between bDMARDs. Disclosure  K. Lauper: Honoraria; Gilead-Galapagos. Grants/research support; AbbVie. Other; AbbVie, Pfizer. L. Kearsley-Fleet: None. R. Davies: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; AbbVie. Grants/research support; Pfizer, BMS.

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

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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