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.

scholarly journals POS1020 EFFICACY OF TOFACITINIB ON DACTYLITIS IN INDIVIDUAL DIGITS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 777.2-778
Author(s):  
A. M. Orbai ◽  
P. J. Mease ◽  
P. Helliwell ◽  
O. Fitzgerald ◽  
M. Bdewi ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Research Support ◽  
Two Phase ◽  
Janus Kinase Inhibitor ◽  
Treatment Groups ◽  
Link Type ◽  
Hands And Feet ◽  
Post Hoc

Background:Dactylitis, a hallmark of psoriatic arthritis (PsA), is a uniformly diffuse and sometimes painful swelling of the fingers and/or toes.1 Up to 50% of patients (pts) with PsA may experience dactylitis;1,2 as such, dactylitis is an accepted domain of PsA that should be considered in treatment decisions.3 In PsA, dactylitis typically involves feet more than hands; dactylitic joints more frequently have erosive damage, compared with non-dactylitic joints.2 There remains a need for effective therapies to treat dactylitis in pts with PsA. Improvements in dactylitis have been associated with tofacitinib, an oral Janus kinase inhibitor for the treatment of PsA.4,5Objectives:To assess the effect of tofacitinib on dactylitis by location (hands/feet) and individual digit involvement in pts with PsA.Methods:These post hoc analyses used data pooled from two Phase 3 studies (12-month OPAL Broaden [NCT01877668];5 6-month OPAL Beyond [NCT01882439]4) in pts with active PsA treated with tofacitinib 5 mg twice daily (BID; approved dose; to Month [M] 6), tofacitinib 10 mg BID (to M6) or placebo (PBO; to M3); pts were treated continuously with a single conventional synthetic disease-modifying antirheumatic drug. Pts were categorised by the presence of dactylitis at baseline (BL) in the hands and/or feet. Endpoints included change from BL in Dactylitis Severity Score (DSS),6 the number of dactylitic digits and the proportion of pts with dactylitis in individual digits at M1, M3 and M6. Descriptive statistics were generated by visit and treatment arm.Results:Data were pooled from 373 pts with DSS >0 at BL. BL characteristics, including gender, age, race, body mass index, PsA duration, BL DSS and dactylitic digits count were similar across dactylitis groups and treatment groups, except for pts with dactylitis in both the hands and feet, who had higher DSS compared to those with dactylitis in the hands or feet only, likely due to having more dactylitic digits (data not shown). Regardless of location, pts treated with tofacitinib had cumulative improvements from BL to M6 in DSS (Figure 1a) and in the number of dactylitic digits (Figure 1b); improvements in DSS were greater at M1 and M3, compared with PBO. Pts treated with tofacitinib 10 mg BID typically had numerically greater improvements in DSS, compared with pts treated with tofacitinib 5 mg BID (Figure 1a). Most pts treated with tofacitinib experienced improvement of dactylitis across all fingers and toes (Figure 1c–f); mean dactylitis presence was ≤15% at M6 in pts treated with tofacitinib for all digits. Generally, at M1 and M3, fewer pts treated with tofacitinib had dactylitis in any digit, compared with PBO (Figure 1c–f).Conclusion:Among pts with pre-existing dactylitis, treatment with tofacitinib resulted in improvements in dactylitis in hands, feet, or both, and in all digits as early as M1, and up to M6.References:[1]Kaeley et al. Semin Arthritis Rheum 2018; 48: 263-273.[2]Brockbank et al. Ann Rheum Dis 2005; 64: 188-190.[3]Coates et al. Arthritis Rheumatol 2016; 68: 1060-1071.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[5]Mease et al. N Engl J Med 2017; 377: 1537-1550.[6]Helliwell et al. J Rheumatol 2005; 32: 1745-1750.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Horizon, Janssen, Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer Inc, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer Inc, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis and Pfizer Inc, Mohammed Bdewi Speakers bureau: AbbVie, Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

scholarly journals AB0831 COMPARISON OF DIFFERENT REMISSION INDICES IN PATIENTS WITH PSORIATIC ARTHRITIS: A POST HOC ANALYSIS OF DATA FROM PHASE 3 TOFACITINIB STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1720-1721
Author(s):  
E. Schneeberger ◽  
G. Citera ◽  
P. Nash ◽  
J. S. Smolen ◽  
P. J. Mease ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Janus Kinase ◽  
Research Support ◽  
Phase 3 ◽  
Low Disease Activity ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Moderate Agreement ◽  
Post Hoc

Background:An international task force has agreed that remission and low disease activity (LDA) are treatment targets for patients (pts) with PsA, and recommends the Disease Activity Index in Psoriatic Arthritis (DAPSA) and minimal disease activity (MDA) to assess disease activity states.1Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:In this post hoc analysis, we compared DAPSA LDA with MDA, and DAPSA remission with very low disease activity (VLDA) and DAS28-3(CRP) remission, in pts with PsA receiving tofacitinib.Methods:Data were pooled from 2 Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]) for pts receiving tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO). DAPSA was determined by summing: swollen joint count (SJC66); tender/painful joint count (TJC68); Patient’s Global Assessment of Arthritis (PtGA; visual analogue scale [VAS]); pain (VAS); and CRP. Pts were classified as achieving MDA or VLDA when meeting ≥5 (MDA) or 7 (VLDA) of the following criteria: TJC68 ≤1; SJC66 ≤1; Psoriasis Activity and Severity Index ≤1 or body surface area ≤3%; pain (VAS) ≤15; PtGA (VAS) ≤20; HAQ-DI ≤0.5; tender entheseal points (using Leeds Enthesitis Index [LEI]) ≤1. A logistic regression model was used to assess demographic and baseline characteristics as predictors of a trend in DAPSA scores at Month (M)3. DAPSA LDA (≤14), MDA, DAPSA remission (DAPSA ≤4), VLDA and DAS28-3(CRP) remission (DAS28-3[CRP]<2.6) rates were compared at M1, M3 and M6 for pts receiving tofacitinib 5 mg BID and at M6 for pts receiving tofacitinib 5 or 10 mg BID. Agreement between disease activity indices at M6 was evaluated using a kappa test. The percentage of tofacitinib-treated pts who achieved MDA, VLDA and non-response was reported at M6, stratified by achievement of DAPSA LDA, remission or non-response.Results:This analysis included 709 pts: tofacitinib 5 mg BID, n=237; tofacitinib 10 mg BID, n=236; PBO, n=236. At M3, older patients treated with tofacitinib, and tofacitinib- or PBO-treated pts with higher baseline SJC66, TJC68, PtGA VAS, HAQ-DI, LEI and Pain VAS, were significantly (p<0.05) more likely to have higher DAPSA. DAPSA LDA, MDA, remission (DAPSA and DAS28-3[CRP]) and VLDA rates generally increased from M1 to M6 for patients receiving tofacitinib 5 mg BID (Figure a). At M6, most tofacitinib-treated pts who achieved MDA, and all who achieved VLDA, were also in DAPSA remission or LDA (Figure b). At least moderate agreement (defined by kappa values 0.41–0.60) was observed between DAPSA LDA and MDA, and between DAPSA remission and VLDA, with both doses of tofacitinib at M6 (Figure c).Conclusion:Remission and LDA rates generally increased over time in pts with PsA receiving tofacitinib. DAPSA LDA showed moderate agreement with MDA, and DAPSA remission showed at least moderate agreement with VLDA, confirming that DAPSA and MDA are useful measurement tools to assess disease activity in pts with PsA treated with tofacitinib.References:[1]Smolen et al. Ann Rheum Dis 2018;77:3-17.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Emilce Schneeberger: None declared, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer 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, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Enrique Soriano Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Speakers bureau: AbbVie, Amber, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, Roche, Claudia Helling Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette E Szumski 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, Dario Ponce de Leon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

scholarly journals Performance of 3 Enthesitis Indices in Patients with Peripheral Spondyloarthritis During Treatment with Adalimumab

2017 ◽  
Vol 44 (5) ◽  
pp. 599-608 ◽  
Author(s):  
Philip J. Mease ◽  
Filip Van den Bosch ◽  
Joachim Sieper ◽  
Yinglin Xia ◽  
Aileen L. Pangan ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Treatment Response ◽  
Femoral Condyle ◽  
Scoring Systems ◽  
Open Label ◽  
Lateral Epicondyle ◽  
Link Type ◽  
Peripheral Spondyloarthritis ◽  
Discriminatory Capacity ◽  
New Onset

Objective.To evaluate the validity of enthesitis indices in patients with peripheral spondyloarthritis (pSpA).Methods.The ABILITY-2 study evaluated the efficacy of adalimumab (ADA) versus placebo (PBO) in patients with active pSpA over 12 weeks. Patients received open-label ADA for an additional 144 weeks. Twenty-nine enthesitis sites used in 3 enthesitis scoring systems [Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index, Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)] were assessed; discriminatory capacity and treatment response at Week 12 were calculated by standardized mean difference (SMD) and Guyatt’s effect size (ES). Sites showing resolution or new-onset enthesitis from baseline to Week 12 were analyzed.Results.Overall, 165 patients (ADA, n = 84; PBO, n = 81) were randomized; 143 had ≥ 1 enthesitis site at baseline. The LEI (SMD −0.73, ES −1.07) and SPARCC (SMD −0.56, ES −0.99) enthesitis indices showed higher discriminatory ability and treatment response than MASES (SMD −0.32, ES −0.81). At Week 12, among sites that were positive at baseline, significantly more (p < 0.05) showed resolution among patients treated with ADA versus PBO in the Achilles tendon (60.4% and 36.5%, respectively), medial epicondyle (73.2%, 48.7%), lateral epicondyle (80.6%, 52.8%), and iliac crest (73.5%, 47.2%). Among negative sites at baseline, significantly less (p < 0.05) new-onset enthesitis was observed with ADA versus PBO for Achilles tendon (3.6% and 10.9%, respectively), greater trochanter (3.4%, 14.4%), lateral epicondyle humerus (4.7%, 15.1%), medial femoral condyle (1.6%, 9.2%), and quadriceps insertion superior patella (1.5%, 7.0%).Conclusion.The LEI and SPARCC enthesitis indices showed better discriminatory capacity and treatment response in patients with pSpA versus MASES, likely because these indices contain more peripheral sites. Trial registration number: ClinicalTrials.govNCT01064856.

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

scholarly journals SAT0398 PERSISTENCE OF USTEKINUMAB (UST) OR TNF INHIBITOR (TNFI) TREATMENT IN PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE LARGE, PROSPECTIVE, MULTINATIONAL, REAL-WORLD PsABio COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1149-1150
Author(s):  
L. Gossec ◽  
S. Siebert ◽  
P. Bergmans ◽  
K. De Vlam ◽  
E. Gremese ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Real World ◽  
Treatment Effect ◽  
Cox Model ◽  
Tnf Inhibitor ◽  
Skin Involvement ◽  
Research Support ◽  
Treatment Persistence ◽  
Kaplan Meier ◽  
Significant Difference

Background:Several biologic DMARDs (bDMARDs) exist for PsA, TNFi and UST being the earliest on European markets. When bDMARDs are insufficiently effective, later-line bDMARDs typically have shorter persistence. Treatment persistence reflects a mix of effectiveness and adverse events (AEs), and persistence data are limited in PsA.Objectives:Comparative analysis of 1-year persistence of UST and TNFi within the prospective PsABio cohort.Methods:PsABio is an observational, multinational study of PsA patients (pts) treated with 1st to 3rd line UST or TNFi at their rheumatologist’s discretion.1Treatment persistence (up to 15 months of follow-up) was defined as time between start of first bDMARD treatment in PsABio, and either stop or switch to another bDMARD, or withdrawal.Persistence of UST and TNFi is shown by Kaplan-Meier curves and compared using Cox regression analysis, with propensity score (PS) to adjust for baseline imbalanced demographic and disease-related covariates (age, sex, bDMARD line, BMI, Clinical Disease Activity index for PSoriatic Arthritis [cDAPSA], 12-item PsA Impact of Disease [PsAID-12], Fibromyalgia Rapid Screening Tool [FiRST] score, co-treatments with MTX, NSAIDs, glucocorticoids, cardiovascular/metabolic comorbidities, dactylitis, enthesitis and body surface area [BSA]). Factors including concomitant MTX use and skin involvement: <3%, 3–10% and >10%, were added to the Cox model to investigate their impact on the PS-adjusted treatment effect.Results:Of 438 and 455 pts who started UST and TNF, respectively, 121 (28%) and 134 (29%) stopped or switched treatment before Month 15, with differences (as expected) according to treatment line (Fig. 1a, b). Reasons for stop/switch were related to safety/AEs in 12% (UST) and 28% (TNFi), and effectiveness (joints, nails or skin) in 77% (UST) and 69% (TNFi) of pts.The observed mean time on drug was 397 days for UST and 385 days for TNFi pts (1st line 410/397 days, 2nd 390/382 days, 3rd 381/338 days). Fig. 1b shows similar persistence for all drugs and treatment lines, except for lower persistence in TNFi 3rd line vs 1st/2nd. In PS-adjusted Cox analysis, no statistically significant difference between UST and TNFi persistence was seen; hazard ratio (HR; 95% CI) for stop/switch bDMARD (UST vs TNFi) was 0.82 (0.60, 1.13). In the model, bDMARD monotherapy (without MTX) and extensive skin involvement (BSA >10%), showed significantly better persistence for UST (HR 0.61 [0.42, 0.90] and 0.41 [0.19, 0.89] respectively; unadjusted Kaplan-Meier graphs shown in Fig. 1c, d). MTX co-therapy and low BSA did not affect the PS-adjusted treatment effect. Other factors added to the PS-adjusted Cox model did not show significant effects.Conclusion:In this real-world PsA cohort undergoing bDMARD treatment, persistence was generally comparable for UST and TNFi, but some clinical situations led to better drug persistence with UST compared to TNFi – particularly monotherapy, more extensive skin involvement, and in 3rd-line treatment. Our data emphasise the importance of skin involvement for pts with PsA.References:[1]Gossec L, et al.Ann Rheum Dis. 2018;77(suppl 2):Abstract AB0928Acknowledgments:This study was funded by Janssen.Disclosure 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, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi

THU0373 SECUKINUMAB DOSE ESCALATION ON ACR RESPONSES IN ANTI-TUMOUR NECROSIS FACTOR NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS: 2-YEAR DATA FROM THE PHASE 3 FUTURE 4 AND FUTURE 5 STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 418.1-419
Author(s):  
P. Emery ◽  
M. Ǿstergaard ◽  
L. C. Coates ◽  
A. Deodhar ◽  
E. Quebe-Fehling ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Tumour Necrosis Factor ◽  
Dose Escalation ◽  
Tumour Necrosis ◽  
Research Support ◽  
Phase 3 ◽  
Post Dose ◽  
Link Type ◽  
Necrosis Factor

Background:Secukinumab (SEC) 150 and 300 mg doses are approved for the treatment of psoriatic arthritis (PsA). SEC 300 mg is the recommended dose for patients (pts) with concomitant moderate-to-severe plaque psoriasis or who are anti-tumour necrosis factor (TNF) inadequate responders. An increase from 150 mg to 300 mg has been reported to be beneficial in some patients with a suboptimal response to SEC 150 mg.1Here, we present a post hoc analysis in anti-TNF naïve pts who escalated from SEC 150 to 300 mg dose in two Phase 3 studies, FUTURE 4 (NCT02294227) and FUTURE 5 (NCT02404350).Objectives:To evaluate the clinical efficacy on joints following dose escalation from SEC 150 to 300 mg on ACR responses in anti-TNF naïve pts with PsA.Methods:Study design, patient inclusion and exclusion criteria of the FUTURE 4 and FUTURE 5 studies have been reported previously.1–3In FUTURE 4, 341 pts were randomised in a 1:1:1 ratio to SEC 150 mg with loading dose (LD), SEC 150 mg without LD, or placebo. In FUTURE 5, 996 pts were randomised in a 2:2:2:3 ratio to SEC 300 mg with LD, SEC 150 mg with LD, SEC 150 mg without LD or placebo. Following a protocol amendment, pts were allowed to escalate from 150 mg to the 300 mg dose, in the event of suboptimal response based on investigator’s judgment, starting at Week 36 in FUTURE 4 and at Week 52 in FUTURE 5. ACR responses in anti-TNF naïve pts were evaluated pre- and up to 32 and 40 weeks post-escalation, in FUTURE 4 and FUTURE 5, respectively: pts were grouped into four ranges based on their response: no (< 20); low (≥ 20 to < 50); moderate (≥ 50 to < 70); high (≥ 70) ACR responses. Data presented are as observed in the Sankey-style overlay plot.Results:Dose escalation from SEC 150 to 300 mg occurred in 136 pts in FUTURE 4 and in 236 pts in FUTURE 5. The proportion of ACR responders increased and the proportion of non-responders decreased in anti-TNF naïve pts who escalated from SEC 150 to 300 mg in the two studies. The proportion of anti-TNF naïve pts with a response ≥ACR50 increased from 20% to 41% in FUTURE 4 and 28% to 46% in FUTURE 5, post dose escalation. The ACR responses in anti-TNF naïve pts up to 40 weeks after escalation from SEC 150 to 300 mg are presented in the Sankey-style overlay (Figure).Figure.ACR Response bar chart with Sankey-style overlays up to 40 weeks, after dose escalation from SEC 150 mg to 300 mg, in anti-TNF naïve pts in FUTURE 4 and 5Conclusion:The proportion of ACR responders increased within 12-16 weeks and was sustained up to 40 weeks following dose escalation in anti-TNF naïve pts with PsA. These results suggest that dose escalation from SEC 150 to 300 mg may be beneficial in anti-TNF naïve pts with a suboptimal response on SEC 150 mg.References:[1]Kivitz AJ, et al. Rheumatol Ther. 2019;6(3):393–407;[2]Mease PJ, et al. Ann Rheum Dis. 2018;77:890–7;[3]Mease, P.J., et al. ACR Open Rheumatology. 2019 [ePub ahead of print] doi:10.1002/acr2.11097.Disclosure of Interests:Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Laura C Coates: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis, Employee of: Novartis, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB

Treatment with tofacitinib in refractory psoriatic arthritis. National multicenter study of the first 87 patients of clinical practice

2021 ◽  
pp. jrheum.201204
Author(s):  
Eva Galíndez-Agirregoikoa ◽  
Diana Prieto-Peña ◽  
José Luis Martín-Varillas ◽  
Beatriz Joven ◽  
Olga Rusinovich ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Psoriatic Arthritis ◽  
Multicenter Study ◽  
Randomized Clinical Trials ◽  
Retention Rate ◽  
Gastrointestinal Symptoms ◽  
Janus Kinase ◽  
Dose Effect ◽  
Open Label ◽  
Reactive Protein

Objective Tofacitinib (TOFA) is the first Janus kinase (JAK) inhibitor approved for Psoriatic Arthritis (PsA). It has shown efficacy in patients refractory to anti-TNFα in Randomized Clinical Trials (RCT). Our aim was to assess efficacy and safety of TOFA in clinical practice. Methods Observational, open-label multicenter study of PsA patients treated with TOFA due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, sparing corticosteroid-dose effect, retention rate and safety. Comparative study of clinical features between our cohort of patients and those from the OPAL BEYOND trial was performed. Results 87 patients (28 women/59 men), mean age of 52.8±11.4 years. All patients were refractory to b-DMARDs and/or to cs-DMARDs plus Apremilast. TOFA was started at 5mg twice daily after a mean follow-up of 12.3±9.3 years from PsA diagnosis. At first month, DAS28ESR decreased from 4.8 [4.1-5.4] to 3.7 [2.8-4.7] (p <0.01), DAPSA from 28 [18.4-34.1] to 15.5 [10.1-25.7] (p < 0.01) and C-reactive protein from 1.9 [0.3-5.0] to 0.5 [0.1-2.2] mg/dL (p < 0.01). Also, TOFA led to a significant reduction of prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOFA retention rate at month 6 was 77% (CI 95%; 65.2-86.3 %). Patients of clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL BEYOND trial. Conclusion Data from clinical practice confirm that TOFA seems to be effective, rapid and relatively safe in refractory PsA despite clinical differences with patients in RCT.

scholarly journals Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

2014 ◽  
Vol 41 (5) ◽  
pp. 837-852 ◽  
Author(s):  
Jürgen Wollenhaupt ◽  
Joel Silverfield ◽  
Eun Bong Lee ◽  
Jeffrey R. Curtis ◽  
Susan P. Wood ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Incidence Rate ◽  
Kinase Inhibitor ◽  
Safety Data ◽  
Janus Kinase ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Safety And Efficacy ◽  
Mean Values ◽  
Link Type

Objective.To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).Methods.Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.Results.Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66–3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.Conclusion.Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: 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. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

scholarly journals Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011207
Author(s):  
Renato Mantegazza ◽  
Gil I. Wolfe ◽  
Srikanth Muppidi ◽  
Heinz Wiendl ◽  
Kenji P. Fujita ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Controlled Trial ◽  
Open Label ◽  
Post Intervention ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Open Label Extension ◽  
Anti Acetylcholine

ObjectiveTo evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) to achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 87.1% of patients achieved improved status and 57.1% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionsEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.Classification of evidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.Trial registrationREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624 (ClinicalTrials.gov).

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