scholarly journals AB0827 IMPACT OF BASELINE BODY MASS INDEX ON THE EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1717.2-1718
Author(s):  
C. T. Ritchlin ◽  
A. Ogdie ◽  
J. T. Giles ◽  
J. J. Gomez-Reino ◽  
P. Helliwell ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Efficacy And Safety ◽  
Lipid Levels ◽  
Research Support ◽  
Link Type ◽  
Advanced Therapies

Background:Obesity is highly prevalent in PsA (~45%)1and is associated with a reduced response to TNF inhibitors.2Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This post hoc analysis assessed tofacitinib efficacy and safety in patients (pts) with PsA by baseline (BL) body mass index (BMI) category.Methods:Data were pooled from two placebo (PBO)-controlled, double-blind, Phase 3 studies in pts with active PsA and an inadequate response to ≥1 conventional synthetic DMARD (OPAL Broaden [12 months;NCT01877668]) or to ≥1 TNF inhibitor (OPAL Beyond [6 months;NCT01882439]).3,4This analysis included pts randomised to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or PBO, stratified by BL BMI: <25 kg/m2, ≥25–<30 kg/m2, ≥30–<35 kg/m2, or ≥35 kg/m2. Efficacy and safety were reported to Month (M)3. M3 efficacy outcomes included ACR20/50/70 and HAQ-DI responses, dactylitis and enthesitis resolution rates and changes from BL in HAQ-DI, Short Form-36 Version 2 (SF-36v2) Physical (PCS) and Mental Component Summary (MCS) scores, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores. Safety outcomes included adverse events (AEs), such as cardiovascular (CV) events and changes in lipid levels and liver function tests (LFTs).Results:This analysis included 710 pts; 43.8% were obese (BMI ≥30). At BL, 161 (22.7%) pts had a BMI <25, 238 (33.5%) had a BMI ≥25–<30, 186 (26.2%) had a BMI ≥30–<35 and 125 (17.6%) had a BMI ≥35. Most pts were white (92.5–96.8%), middle-aged (mean: 44.5–51.2 yrs) and female (49.5–65.6%). Greater proportions of obese pts were from Russia/Eastern Europe (35.0%) and USA/Canada (31.8%), vs the rest of world. At BL, higher BMI correlated with an increased prevalence of metabolic syndrome (4.3% in BMI <25 to 76.0% in BMI ≥35) and CRP levels >2.87 mg/L (49.1% in BMI <25 to 84.0% in BMI ≥35). Higher proportions of pts (42.5–47.9%) in BL BMI categories <35 reported no prior biologic DMARD use, vs pts with a BL BMI ≥35 (33.6%). At M3, efficacy improvements were greater in tofacitinib-treated pts vs PBO-treated pts (Figure 1). In pts with a BL BMI ≥35, a trend towards fewer pts responding was observed (Figure 1) and mean changes from baseline in SF-36v2 PCS and MCS and FACIT-F generally appeared lower (Figure 2) vs pts in lower BL BMI categories. Up to M3, the proportions of pts with AEs, and percentage change from BL in lipid levels and LFTs, were generally similar across all BL BMI categories. Three CV events were reported: non-fatal cerebrovascular accident, transient ischemic attack (both tofacitinib 5 mg BID, BMI ≥30–<35) and coronary artery revascularisation (PBO; BMI ≥35). Limitations include the 3-month observation time, particularly for safety findings, thus longer observation times are warranted.Conclusion:Regardless of BL BMI, tofacitinib demonstrated greater efficacy than PBO at M3 in pts with PsA. Similar to other advanced therapies,2reduced efficacy was generally observed in tofacitinib and PBO pts with a BL BMI ≥35. Tofacitinib safety appeared consistent across all BL BMI categories.References:[1]Labitigan et al. Arthritis Care Res (Hoboken) 2014;66:600-07.[2]Singh et al. PLoS One 2018;13:e0195123.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.Acknowledgments:Medical writing support was provided by Mark Bennett of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexis Ogdie Shareholder of: Amgen, Novartis, Pfizer Inc, Grant/research support from: Novartis, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Jon T Giles Grant/research support from: Pfizer Inc, Juan Jesus Gomez-Reino Grant/research support from: AbbVie, Novartis, Pfizer Inc, Roche, UCB, Consultant of: Pfizer Inc, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, UCB, Philip Helliwell: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Wael Joseph Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniela Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ana Belen Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

The Relation of Body Mass Index to Biochemical Parameters and Profile of Heart Failure

2018 ◽  
Vol 69 (7) ◽  
pp. 1673-1677
Author(s):  
Viviana Aursulesei ◽  
Andrei Manta ◽  
Razan Al Namat ◽  
Monica Hugianu ◽  
Angela Maria Moloce ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Body Mass Index ◽  
Body Mass ◽  
Patient Selection ◽  
Biochemical Parameters ◽  
Obesity Paradox ◽  
Lipid Levels ◽  
Randomized Control ◽  
Selection Parameters

The bidirectional relation between body mass index (BMI) and heart failure (HF) is complex and not fully understood. The obesity paradox phenomena is controversial and related to patient selection, parameters used for defining abnormal weight, characteristics of HF. Our study sustain the importance of controlling risk factors, in particular plasma glucose, lipid levels, as well as hypertension in patients with HF and BMI over 25 kg/m2. Also, in contrast to the randomized control studies our results can only partially support data related to obesity paradox phenomena.

scholarly journals POS1038 THE EFFECT OF FILGOTINIB ON ENTHESITIS: 100-WEEK DATA FROM AN OPEN-LABEL EXTENSION STUDY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 792.2-793
Author(s):  
P. Helliwell ◽  
L. C. Coates ◽  
F. Van den Bosch ◽  
D. D. Gladman ◽  
L. Gheyle ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Treatment Effect ◽  
Janus Kinase ◽  
Research Support ◽  
Rapid Improvement ◽  
Open Label ◽  
Lateral Epicondyle ◽  
Link Type ◽  
Open Label Extension ◽  
Discriminatory Capacity

Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.References:[1]Mease P, et al. Lancet 2018;392:2367–77[2]Mease P, et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0910Figure 1.Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Eline Vetters, Leen Gilles, Benjamin Pett and his team, all employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Philip Helliwell Speakers bureau: Janssen, Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB.

Alirocumab efficacy and safety by body mass index: Pooled analysis from 10 Phase 3 ODYSSEY trials

2018 ◽  
Vol 275 ◽  
pp. e53-e54
Author(s):  
F. Tinahones ◽  
U. Laufs ◽  
B. Cariou ◽  
J. Yang ◽  
M.J. Louie ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Pooled Analysis ◽  
Efficacy And Safety ◽  
Phase 3

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants for Atrial Fibrillation Across Body Mass Index Categories

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rachel M. Kaplan ◽  
Yoshihiro Tanaka ◽  
Rod S. Passman ◽  
Michelle Fine ◽  
Laura J. Rasmussen‐Torvik ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Body Mass ◽  
Intracranial Hemorrhage ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Class 1 ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Background Direct‐acting oral anticoagulants are now the preferred method of anticoagulation in patients with atrial fibrillation. Limited data on efficacy and safety of these fixed‐dose regimens are available in severe obesity where drug pharmacokinetics and pharmacodynamics may be altered. The objectives of this study were to evaluate efficacy and safety in patients with atrial fibrillation taking direct‐acting oral anticoagulants across body mass index (BMI) categories in a contemporary, real‐world population. Methods and Results We performed a retrospective study of patients with atrial fibrillation at an integrated multisite healthcare system. Patients receiving a direct‐acting oral anticoagulant prescription and ≥12 months of follow‐up between 2010 and 2017 were included. The primary efficacy and safety outcomes were ischemic stroke or systemic embolism and intracranial hemorrhage. We performed Cox proportional hazards modeling to compute hazard ratios (HRs) adjusted for CHA 2 DS 2 ‐VASc score to examine differences by excess BMI categories relative to normal BMI. Of 7642 patients, mean±SD age was 69±12 years with a median (interquartile range) follow‐up of 3.8 (2.2–6.0) years. Approximately 22% had class 1 obesity and 19% had class 2 or 3 obesity. Stroke risks were similar in patients with and without obesity (HR, 1.2; 95% CI, 0.5–2.9; and HR, 0.68; 95% CI, 0.23–2.0 for class 1 and class 2 or 3 obesity compared with normal BMI, respectively). Risk of intracranial hemorrhage was also similar in class 1 and class 2 or 3 obesity compared with normal BMI (HR, 0.64; 95% CI, 0.35–1.2; and HR, 0.66; 95% CI, 0.35–1.2, respectively). Conclusions Direct‐acting oral anticoagulants demonstrated similar efficacy and safety across all BMI categories, even at high weight values.

scholarly journals P210 Efficacy and safety of filgotinib for patients with RA with inadequate response to methotrexate: FINCH1 primary outcome results

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
David Walker ◽  
Bernard G Combe ◽  
Alan J Kivitiz ◽  
Yoshiya Tanaka ◽  
Désirée van der Heijde ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Study Drug ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Mixed Effect ◽  
Patient Reported

Abstract Background Filgotinib (FIL) is an oral, potent, selective Janus kinase 1 inhibitor that has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA). The objective of this study was to evaluate efficacy and safety of FIL treatment in patients with RA who have had an inadequate response to methotrexate (MTX). Methods This Phase 3, double-blind, active- and placebo (PBO)-controlled study randomised patients with active RA (3:3:2:3) to FIL 200mg, FIL 100mg, adalimumab [ADA] 40mg every 2 weeks, or PBO daily for up to 52 weeks; results through week 24 are presented. Patients also received background MTX. Primary efficacy endpoint was proportion of patients achieving ACR20 at week 12; additional clinical assessments included ACR50 and ACR70 and DAS28-CRP score ≤3.2 and &lt;2.6, and patient-reported outcomes including HAQ-DI. Safety endpoints included adverse event types and rates. Logistic regression was used for superiority test of FIL vs PBO for ACR response and other binary endpoints, while mixed-effect model for repeated measures (MMRM) were used for continuous endpoints. Non-inferiority test of FIL to ADA (preserving &gt;50% of ADA response) was performed for DAS28-CRP ≤3.2 and &lt;2.6. Results Of 1,759 patients randomised, 1,755 received study drug: 475 FIL 200mg; 480 FIL 100mg; 325 ADA; and 475 PBO, of which 89.5%, 90.4%, 88.9%, and 81.3%, respectively, completed 24 weeks of study drug. 81.8% were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.6) years, and mean (SD) DAS28-CRP was 5.7 (0.9). At week 12, significantly more patients in the FIL 200mg and 100mg arms achieved an ACR20 improvement vs PBO (Table 1). More patients receiving FIL achieved ACR50 and ACR70 improvements, DAS28-CRP scores ≤3.2 and &lt;2.6 and reported improvements in HAQ-DI scores versus PBO (Table 1). Non-inferiority of FIL 200mg to ADA was met based on DAS28-CRP ≤3.2. The FIL safety profile was consistent with prior studies through Week 24. Conclusion FIL 200mg and 100mg led to significant improvement in signs and symptoms of RA, prevented radiographic progression, improved physical function compared to PBO, and was well-tolerated. Efficacy of FIL 200mg was non-inferior to ADA based on DAS28-CRP ≤3.2. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. B.G. Combe: Honoraria; Received honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. A.J. Kivitiz: Consultancies; Consultant to AbbVie, Celgene, Horizon, Jansses, Merck, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim, Flexion and Novartis. Shareholder/stock ownership; Shareholder of Novartis. Y. Tanaka: Honoraria; Honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly ans Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, Ono, Astellas, Eli Lilly, Pfizer, Abbvi and YL. D. van der Heijde: Corporate appointments; Director of Imaging Rheumatology bv. Consultancies; Consultant for consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: Corporate appointments; Employee of Gilead Sciences, Inc.. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. N. Mozaffarian: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R.B.M. Landewé: Consultancies; Consultant for AbbVie, AstraZeneca, BMS, Galapagos, Pfizer, Eli Lilly, Novartis, and UCB.. S. Bae: None. E.C. Keystone: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer,, PuraPharm, Sandoz, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. P. Nash: Consultancies; Consultant for AbbVie, BMS, Jansses, Pfizer, Roche, Lilly, Sanofi, MSD, Novartis, Celgene and Gilead.

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