scholarly journals P242 CZP improves work and household productivity and social participation over 1 year of treatment in patients with non-radiographic axSpA

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Karl Gaffney ◽  
Atul Deodhar ◽  
Lianne Gensler ◽  
Jonathan Kay ◽  
Walter Maksymowych ◽  
...  
Keyword(s):  
Social Participation ◽  
Certolizumab Pegol ◽  
Specific Work ◽  
Inadequate Response ◽  
Research Support ◽  
Open Label ◽  
Double Blind ◽  
Research Grants ◽  
Household Productivity ◽  
The Impact

Abstract Background Certolizumab pegol (CZP) treatment has been shown to significantly improve work and household productivity and social participation compared to placebo in active non-radiographic axial spondyloarthritis (nr-axSpA) patients up to 24 weeks. Here, we report the impact of CZP in combination with non-biologic background medication (NBBM) on signs and symptoms of nr-axSpA compared to placebo+NBBM. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicentre study including a 52-week double-blind, placebo-controlled period (completed). Patients had active nr-axSpA, objective signs of inflammation (OSI; elevated CRP and/or positive MRI of the sacroiliac joint), previous inadequate response to ≥ 2 NSAIDs and were randomised 1:1 to CZP (400 mg at Weeks 0/2/4, then 200 mg every 2 weeks) or placebo. The validated arthritis-specific Work Productivity Survey (WPS) assessed the impact of nr-axSpA on work and household productivity and social participation. Missing data were imputed using last observation carried forward (LOCF) post hoc in the Full Analysis Set (randomised patients who received ≥1 dose of CZP). Results 317 patients were randomised (CZP: 159; placebo: 158). Mean age at baseline was 37.3 years and 51.4% of patients were female. At baseline, most patients were employed (CZP: 124 [77.8%]; placebo: 123 [78.0%]) and reported a mean 3.7 (CZP) and 3.5 (placebo) workdays missed per month due to disease (Table 1). By Week 12, work absenteeism substantially improved in the CZP group compared with placebo (0.9 vs 2.1 days missed per month, LOCF), with further improvements at Week 52 (0.3 vs 2.0 days missed per month, LOCF). Between Week 12 and Week 52, most placebo patients (104, 65.8%) switched to open-label CZP, impacting Week 52 imputed outcomes. Despite this, similar patterns of improvement following CZP treatment were seen for absenteeism, workdays with impaired productivity, household days with missed/reduced productivity and social participation between imputed and observed case data (Table 1). Improvements were similar between male and female patients (data not shown). Conclusion CZP treatment resulted in improvements in work and household productivity and social participation for nr-axSpA patients as early as Week 12 compared to background medication only, with benefits maintained to Week 52. Disclosures K. Gaffney: Other; Research Grants/Consultancy Fees from Abbvie, Biogen, Celgene, Gilead, Izana, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer and UCB. L. Gensler: Consultancies; Galapagos, Eli Lilly and Janssen. Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp & Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. R. Landewé: Consultancies; Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Member of speakers’ bureau; Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Grants/research support; Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. M. Rudwaleit: Consultancies; Abbott, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche, UCB Pharma. S. Hall: Other; Consulting fees/ research grants from AbbVie, Eli Lilly, Novartis, and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. D. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. Other; Director of Imaging Rheumatology BV.

scholarly journals Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

2019 ◽  
Vol 78 (8) ◽  
pp. 1033-1040 ◽  
Author(s):  
Sophie Glatt ◽  
Peter C Taylor ◽  
Iain B McInnes ◽  
Georg Schett ◽  
Robert Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Certolizumab Pegol ◽  
Inadequate Response ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Reactive Protein ◽  
Dual Inhibition

ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

scholarly journals P284 Certolizumab pegol-treated patients with non-radiographic axSpA demonstrate improvements in sleep quality and other patient reported outcomes

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Raj Sengupta ◽  
Lianne Gensler ◽  
Jonathan Kay ◽  
Walter Maksymowych ◽  
Nigil Haroon ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Patient Reported Outcomes ◽  
Sleep Problems ◽  
Certolizumab Pegol ◽  
Spinal Pain ◽  
Controlled Study ◽  
Inadequate Response ◽  
Research Support ◽  
Double Blind ◽  
Patient Reported

Abstract Background Certolizumab pegol (CZP) treatment has demonstrated improvements in multiple manifestations of non-radiographic axial spondyloarthritis (nr-axSpA), including patient-reported outcomes (PROs). Here, we report PROs for nr-axSpA patients treated with CZP or placebo in CaxSpAnd - the first 52-week placebo-controlled study to investigate the efficacy of an anti-TNF agent in patients with active nr-axSpA and objective signs of inflammation. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicenter study including a 52-week double-blind, placebo-controlled period (completed); patients who had an inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs were randomized 1:1 to placebo or CZP (400mg at Weeks 0/2/4, then 200mg every 2 weeks). Clinical PROs included: Sleep Problems Index scores I (6 items) and II (9 items) from the Medical Outcomes Study Sleep Scale (assesses sleep disturbance, adequacy, somnolence, quantity, snoring, and awakening short of breath or with a headache), nocturnal spinal pain (numerical rating scale [NRS]), fatigue (BASDAI Q1), and morning stiffness (average of BASDAI Q5 + 6). Post-hoc analyses of minimal clinically important differences (MCID [≥1-point improvement]) for fatigue and nocturnal spinal pain were conducted. Variables were analyzed using an ANCOVA model including baseline score as a covariate and fixed effects for treatment group, region and MRI/CRP classification. P-values were nominal. Missing values following discontinuation of double-blind treatment were imputed using last observation carried forward. Results 317 patients with nr-axSpA were randomised to CZP (n = 159) or placebo (n = 158); 125 (79%) and 54 (34%) patients, respectively, completed Week 52. CZP-treated patients showed greater improvements (indicated by higher scores) in Sleep Problems Index II scores vs placebo-treated patients at Week 12 (mean change from baseline: 4.8 [CZP] vs 2.2 [placebo]; p < 0.001). Improvements were also seen in other clinical PROs (Table). By Week 12, greater proportions of patients treated with CZP vs placebo experienced at least MCID response in fatigue (85.4% vs 57.6%, respectively) and nocturnal spinal pain (82.8% vs 58.9%, respectively); results were sustained through Week 52. Conclusion CZP-treated nr-axSpA patients showed substantial improvements in sleep quality and other clinical outcomes important to patients; future analyses of these data will explore associations between sleep quality and other clinical PROs. Disclosures R. Sengupta: Other; R.S. has received speaker fees, support for conference attendance and grants from Abbvie, Biogen, Celgene, Novartis, Pfizer and UCB Pharma. L. Gensler: Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma; consulting fees from Galapagos, Eli Lilly and Janssen. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp & Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer and UCB.

scholarly journals OP0104 THE IMPACT OF PERSISTENT INFLAMMATORY CHANGES ON PREVALENCE OF FATTY LESIONS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS TREATED WITH CERTOLIZUMAB PEGOL: 4-YEAR MRI RESULTS FROM RAPID-AXSPA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 67-68
Author(s):  
X. Baraliakos ◽  
S. Kruse ◽  
S. Auteri ◽  
N. De Peyrecave ◽  
T. Nurminen ◽  
...  
Keyword(s):  
Axial Spondyloarthritis ◽  
Certolizumab Pegol ◽  
Controlled Study ◽  
Research Support ◽  
Double Blind ◽  
Inflammatory Status ◽  
Long Term Treatment ◽  
Inflammatory Changes ◽  
The Impact

Background:Axial spondyloarthritis (axSpA) is a chronic disease characterised by inflammation in the sacroiliac joints and spine, causing severe back pain and stiffness. Emerging evidence suggests chronic spinal inflammation may be associated with osteoproliferation leading to syndesmophyte formation and spinal ankylosis, with subsequent worsening of patient mobility and function.1Fatty lesions (FLs) on magnetic resonance imaging (MRI) T1 sequences are considered to be post-inflammatory precursors to these changes. Certolizumab pegol (CZP), an Fc-free, PEGylated tumour necrosis factor inhibitor (TNFi), has proven efficacy in treating the signs and symptoms of axSpA.2,3CZP has also been shown to decrease spinal and sacroiliac joint MRI inflammation, and limit radiographic progression of the spine over 4 years of treatment.4Objectives:To report the effect of early post-baseline (BL) inflammatory changes on fatty lesion prevalence over 4 years in a broad axSpA patient population treated with CZP.Methods:RAPID-axSpA (NCT01087762) was a phase 3 trial which was double-blind and placebo (PBO)-controlled to Week (Wk) 24, dose-blind to Wk 48 and open-label to Wk 204. CZP-randomised axSpA patients (Wk 0 CZP: 200 mg every 2 wks [Q2W] or 400 mg Q4W) continued their assigned dose throughout; PBO-randomised axSpA patients (Wk 0 PBO) received CZP from Wk 24, or if non-responders, from Wk 16 onwards. Blinded spinal MRI scans at Wks 0, 12, 48, 96 and 204 were assessed by 2 central readers to evaluate FL and inflammatory lesions in vertebral edges (VEs). Changes in FL prevalence are reported as odds ratios (OR; FL+/FL-) between time points or inflammation states, with nominal 95% confidence intervals (CI), for Wk 0 CZP. ORs were estimated from a logistic regression model for VE level data with random effects for patient and VE (within patient). The fixed model effects included time point, inflammatory status of VEs at BL and Wk 12, FL status at BL, and interactions if appropriate.Results:Of 325 axSpA patients, 89 and 47 initially randomised to CZP or PBO, respectively, had a BL and ≥1 post-BL MRI and therefore were eligible for these analyses. In these patients, a total of 3,127 of VEs were assessed at BL; inflammation was observed in 21.6% and FL in 29.3% of VEs, equating to mean counts of 5.0 and 6.7 per patient; 10.5% of VEs had both inflammation and FL at BL. At BL, FLs were relatively more often observed in inflamed VEs vs non-inflamed VEs: OR (95% CI) of 3.30 (1.94, 5.61). This difference increased over time, as the OR of FL at Wk 204 vs BL was 2.82 (1.70, 4.66) in VEs that were inflamed at BL compared with 1.08 (0.79, 1.48) in VEs that were not inflamed at BL (Figure 1A). Resolution of inflammation by Wk 12 appeared to lower the risk of FL prevalence over 4 years. When adjusted for BL VE status with respect to inflammation and FL, if inflammation prevailed at Wk 12, the OR of FL vs no FL was 1.80 (0.93, 3.49) at Wk 48, 2.54 (1.32, 4.91) at Wk 96 and 3.91 (1.87, 8.15) at Wk 204 (Figure 1B).Conclusion:This is the first report from a clinical interventional PBO-controlled study in a broad axSpA population showing that inflammation that prevailed after the start of TNFi treatment was associated with increased FL prevalence over 4 years. Reduction of inflammation by Wk 12 mitigated the risk of FL over the long-term, indicating the importance of early, effective and long-term treatment targeting inflammation. Similarly, a complete and persistent reduction of inflammation appears to be critical in these patients.References:[1]Maksymowych WP. Ann Rheum Dis 2013;72:23–8;2.Van der Heijde D. Rheumatology (Oxford) 2017;56:1498–509;3.Deodhar A. Arthritis Rheumatol 2019;71:1101–11;4.Van der Heijde D. Ann Rheum Dis 2018;77:699–705.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Sebastian Kruse: None declared, Simone Auteri Shareholder of: UCB Pharma, Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Tommi Nurminen Employee of: UCB Pharma, Thomas Kumke Employee of: UCB Pharma, Bengt Hoepken Employee of: UCB Pharma, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma

scholarly journals P187 Secukinumab significantly decreased joint synovitis measured by Power Doppler ultrasonography in biologic-naive patients with active psoriatic arthritis: primary (12week) results from a randomised, placebo-controlled Phase 3 study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Maria-Antonietta D'Agostino ◽  
Georg Schett ◽  
Alejandra López Rodríguez ◽  
Ladislav Šenolt ◽  
Jose Maldonado-Cocco ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Repeated Measures ◽  
Doppler Ultrasonography ◽  
Power Doppler ◽  
Power Doppler Ultrasonography ◽  
Research Support ◽  
Open Label ◽  
Double Blind ◽  
Research Grants ◽  
Secondary Endpoints

Abstract Background/Aims  Power Doppler (PD) ultrasonography (PDUS) is a sensitive, non-invasive imaging technology used to assess joint synovitis and enthesitis in psoriatic arthritis (PsA). The European Alliance of Associations for Rheumatology (EULAR) and the Outcome Measures in Rheumatology (EULAR-OMERACT) developed a standardised ultrasonography composite scoring system that is sensitive to change (the global EULAR-OMERACT synovitis score [GLOESS]) to detect and score joint synovitis. We report primary (12-week) efficacy and safety data from ULTIMATE (NCT02662985), the first large, randomised, double-blind, placebo-controlled Phase 3 study to assess the time course of response to subcutaneous secukinumab on joint synovitis with PDUS in PsA. Methods  This 52-week study has a 12-week double-blind treatment period followed by 12week open-label and 6-month open-label extensions. The study recruited biologic-naive patients with active PsA and inadequate response to conventional disease-modifying antirheumatic drug(s), with joint synovitis on PDUS (≥1 joint [of 48] with both total synovitis PDUS score and PD signal ≥2; or ≥ 2 joints with PDUS score ≥2 and PD signal ≥1) at screening and baseline and ≥1 clinical enthesitis site at baseline. Patients received secukinumab (300 or 150 mg) or placebo weekly followed by 4-weekly dosing (from Week 4). The primary endpoint was the difference in mean change in GLOESS from baseline to Week 12 between secukinumab and placebo, determined by mixed-effects model repeated measures analysis. Safety analyses included all patients who received ≥1 dose of study treatment. Results  Of 166 patients enrolled, 96% (160/166) completed 12 weeks of treatment (secukinumab: 99% [82/83]; placebo: 94% [78/83]). Baseline demographics, clinical and ultrasound characteristics were similar across treatment groups. The primary endpoint was met; adjusted mean change in GLOESS was significantly higher with secukinumab than placebo (-9.0 vs -5.8; P = 0.004) at Week 12 (Table 1), with statistical significance seen as early as Week 1. All key secondary endpoints were met. No new or unexpected safety signals were reported. P187 Table 1:Efficacy of secukinumab at Week 12EndpointsSecukinumab (300 mg + 150 mg)a (N = 83)Placebo (N = 83)Difference/OR (95% CI)P valuePrimaryPDUS GLOESS, LS mean change (SE)b,c-9.0 (0.9)-5.8 (0.9)Difference: -3.2d (-5.5; -0.8)0.004SecondaryACR20, % responders6834OR: 4.1e (2.1; 8.0)<0.0001ACR50, % responders469OR: 8.9e (3.6; 22.0)<0.0001SPARCC enthesitis index, LS mean change (SE)c-2.35 (0.28)-1.65 (0.28)Difference: -0.69d (-1.39; -0.002)0.02Data presented as non-responder imputation for binary variables and MMRM for continuous variables.Prespecified primary and secondary endpoints were analysed according to a statistical hierarchy. Endpoints are shown in the order of testing.aPatients with psoriasis >10% of body surface area received 300 mg; remainder received 150 mg;bGLOESS using PDUS composite score of 24 paired joints; the range for the GLOESS is 0-144;cAdjusted means and mean change values are from MMRM including treatment, centre and analysis visit as factors, baseline score and weight as continuous covariates and treatment by analysis visit as an interaction term;dDifference in adjusted mean change;eOR. ACR, American College of Rheumatology; CI, confidence interval; EULAR-OMERACT, European League Against Rheumatism and the Outcome Measures in Rheumatology; GLOESS, global EULAR-OMERACT synovitis score; LS, least squares; MMRM, mixed-effects model repeated measures; N, total number of randomised patients; OR, odds ratio; PDUS, Power Doppler ultrasonography; SE, standard error; SPARCC, Spondyloarthritis Research Consortium of Canada Enthesitis Index. Conclusion  Secukinumab demonstrated a rapid and significant decrease in synovitis over 12 weeks (per GLOESS), and superior efficacy on ACR20/50 responses and SPARCC enthesitis vs placebo at Week 12 in biologic-naive patients with PsA. The safety profile of secukinumab was consistent with previous reports. Disclosure  M. D'Agostino: Honoraria; M-A.D has received speaker/consultancy fees from Sanofi, Novartis, BMS, Celgene, Roche, AbbVie, UCB and Eli Lilly. G. Schett: Honoraria; G.S. has received honoraria from AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche and UCB. A. López Rodríguez: Corporate appointments; A.L.R. is a clinical trial researcher, speaker and consultant for Roche, Eli Lilly, Novartis, BMS and Neovacs. L. Šenolt: Honoraria; L.S. has received speaker's honoraria from AbbVie, Amgen, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., L.S. has received expenses for attendance at advisory board meetings from AbbVie, BMS, Celgene, MSD, Novartis, Pfizer, Roche and UCB., L.S. has received honoraria for clinical trials from AbbVie, Amgen, BMS, Celgene, Novartis, Pfizer, Takeda and UCB. Grants/research support; L.S. has received research grants from AbbVie. J. Maldonado-Cocco: Consultancies; J.M-C. is a speaker/consultant for Pfizer, Merck Sharp & Dohme, Sanofi-Aventis, Novartis, BMS, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly and Gilead. Other; J.M-C. is a clinical researcher as PI in clinical trials for Pfizer, Merck Sharp & Dohme, Sanofi-Aventis, Novartis, BMS, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly and Gilead. R. Burgos-Vargas: None. E. Naredo: Honoraria; E.N. has received speaker fees from AbbVie, Roche, BMS, Pfizer, UCB, Lilly, Novartis, Janssen and Celgene GmbH, and honoraria for clinical trials from AbbVie, Novartis and BMS. Grants/research support; E.N. has received research grants from Lilly. P. Carron: Consultancies; P.C. is a speaker/consultant for Pfizer, Merck Sharp & Dohme, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene Corporation. Grants/research support; P.C. has received research grants from UCB, Merck Sharp & Dohme and Pfizer. M. Boers: Consultancies; M.B. is a consultant for BMS, Novartis, Pfizer, GSK and Mylan. A. Duggan: Other; A-M.D. is an employee of Novartis. P. Goyanka: Other; P.G. is an employee of Novartis. C. Gaillez: Shareholder/stock ownership; C.G. is a shareholder of NVS and BMS. Other; C.G. is an employee of Novartis.

scholarly journals Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study

2014 ◽  
Vol 74 (1) ◽  
pp. 44-51 ◽  
Author(s):  
A Kavanaugh ◽  
D Gladman ◽  
D van der Heijde ◽  
O Purcaru ◽  
P Mease
Keyword(s):  
Psoriatic Arthritis ◽  
Certolizumab Pegol ◽  
Leisure Activities ◽  
Controlled Study ◽  
Social Activities ◽  
Paid Work ◽  
Phase 3 ◽  
Double Blind ◽  
Household Productivity ◽  
The Impact

ObjectivesTo evaluate the effect of certolizumab pegol (CZP) on productivity outside and within the home, and on participation in family, social and leisure activities in adult patients with psoriatic arthritis (PsA).MethodsRAPID-PsA (NCT01087788) is a phase 3, double-blind, placebo-controlled trial. 409 patients with active PsA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). The arthritis-specific Work Productivity Survey (WPS) assessed the impact of PsA on paid work and household productivity, and participation in social activities during the preceding month. WPS responses were compared between treatment arms using a non-parametric bootstrap-t method.ResultsAt baseline, 56.6%, 60.1% and 61.5% of placebo, CZP 200 mg Q2W and CZP 400 mg Q4W patients were employed. By week 24, employed CZP patients reported an average of 1.0–1.8 and 3.0–3.9 fewer days of absenteeism and presenteeism, respectively, per month compared with 1.0 and 0.3 fewer days for placebo patients (p<0.05). Within the home, by week 24, CZP patients reported an average of 3.0–3.5 household work days gained per month versus 1.0 day for placebo (p<0.05). CZP patients also reported fewer days with reduced household productivity or days lost for participation in family, social and leisure activities. Improvements with CZP were seen as early as week 4 and continued to week 24.ConclusionsCZP treatment significantly improved productivity at paid work and within the home, and resulted in greater participation in social activities for PsA patients.Trial registration numberNCT01087788.

scholarly journals Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Messoud Ashina ◽  
Joshua M. Cohen ◽  
Maja Galic ◽  
Verena Ramirez Campos ◽  
Steve Barash ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Medication Use ◽  
Episodic Migraine ◽  
Inadequate Response ◽  
Open Label ◽  
Double Blind ◽  
Moderate Severity ◽  
Preventive Medication ◽  
Open Label Extension ◽  
Acute Headache

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%). Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).

scholarly journals OP0053 SECUKINUMAB IMPROVES CLINICAL AND IMAGING OUTCOMES IN PATIENTS WITH PSORIATIC ARTHRITIS AND AXIAL MANIFESTATIONS WITH INADEQUATE RESPONSE TO NSAIDS: WEEK 52 RESULTS FROM THE MAXIMISE TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 35-36 ◽  
Author(s):  
X. Baraliakos ◽  
L. Gossec ◽  
E. Pournara ◽  
S. Jeka ◽  
R. Blanco ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Controlled Trial ◽  
Spinal Pain ◽  
Inadequate Response ◽  
Imaging Data ◽  
Sacroiliac Joints ◽  
Research Support ◽  
Double Blind ◽  
Randomised Controlled ◽  
Mri Score

Background:Although axial disease may affect up to 70% of patients (pts) with Psoriatic Arthritis (PsA), evidence on the efficacy of biologics in the treatment of axial manifestations in such pts is limited,1particularly as validated classification criteria for this subtype of PsA are not yet available. MAXIMISE (NCT02721966) is the first randomised controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of PsA and showed that secukinumab (SEC) 300 and 150 mg provided rapid and significant improvement in ASAS20 responses in these pts through week (Wk) 12.2Objectives:To present 52 wks efficacy results and imaging data from the MAXIMISE trial.Methods:This phase 3b, double-blind, placebo (PBO)-controlled, multicentre 52-wk trial included 498 pts (aged ≥18 years) with a diagnosis of PsA and classified by CASPAR criteria, spinal pain VAS score ≥ 40/100 and BASDAI score ≥ 4 despite use of at least two NSAIDs. Pts were randomised to SEC 300 mg (N=167) or SEC 150 mg (N=165) or PBO (N=166) wkly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomised to SEC 300/150 mg. The primary endpoint was ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12. Wk 52 data are presented as observed. Bone marrow oedema of the entire spine and sacroiliac joints were assessed centrally with Berlin MRI scores at Baseline, Wk 12 and Wk 52.Results:Primary and key secondary endpoints were met; ASAS20 responses were sustained and increased further through Wk 52. 75%/79.7% of the PBO pts re-randomised at Wk 12 to SEC 300/150 mg achieved ASAS20 response at Wk 52 (Figure 1). ASAS40 responses at Wk 52 were 69.1% [SEC 300 mg], 64.5% [SEC 150 mg], 62.5% [PBO-SEC 300 mg], and 54.1% [PBO-SEC 150 mg]. At baseline, 59.5% [SEC 300 mg], 53.5% [SEC 150 mg] and 64.2% [PBO] of the pts had positive MRIs for the sacroiliac joints and/or the spine with Berlin MRI score ≥1. The reductions of Berlin MRI score for entire spine and sacroiliac joints were statistically significant for pts treated with SEC 300/150 mg vs. placebo (Figure 2a and b). There were no new or unexpected safety findings.Figure 1.ASAS20 Response over 52 Wks*Figure 2.Total Berlin MRI score for the Entire Spine and Sacroiliac Joints at Wk 12Conclusion:Secukinumab improved all evaluated ASAS responses through Wk 52 in PsA pts with axial manifestations and inadequate responses to NSAIDs and led to significant reduction of inflammatory MRI lesions in the spine and the Sacroiliac Joints. The safety profile of secukinumab through Wk 52 was consistent with previous reports.3-4References:[1]McInnes IB, et al.Lancet.2015;386(9999):1137–46.[2]Baraliakos X, et al.Arthritis Rheumatol. 2019;71 (suppl 10).[3]Langley RG, et al.N Engl J Med.2014;371:326–38.[4]Sieper J, et al.Ann Rheum Dis.2016;0:1–8.Acknowledgments:The study was sponsored by Novartis Pharma AG, Basel, Switzerland.Disclosure of Interests:Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Effie Pournara Shareholder of: Novartis, Employee of: Novartis, 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, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Salvatore D’Angelo Consultant of: AbbVie, Biogen, BMS, Celgene, Eli Lilly, MSD, Novartis, and UCB, Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Novartis, Pfizer, and Sanofi, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Barbara Schulz Employee of: Novartis, Michael Rissler Shareholder of: Novartis, Employee of: Novartis, Kriti Nagar Employee of: Novartis, Chiara Perella Shareholder of: Novartis, Employee of: Novartis, Laura C Coates: None declared

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

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