Background Tabalumab is a monoclonal antibody that neutralizes membrane-bound and soluble B cell activating factor (BAFF). Objectives Evaluate efficacy and safety of tabalumab, in RA pts who had an inadequate response to methotrexate (MTX) therapy, in a randomized, double-blind, placebo-controlled study. Methods 1041 RA pts (ITT population) were enrolled in this 52-wk study evaluating 2 subcutaneous (SQ) tabalumab doses (120mg every 4 wks [120/Q4W] or 90mg every 2 wks [90/Q2W]) vs placebo (PBO). At wk 0, pts received a SQ loading dose that was 2 times the treatment dose (240mg, 180mg, or PBO). Eligible pts had moderate-severely active RA despite ongoing MTX. Primary endpoints included ACR20 and HAQ-DI at 24 wks, and change in mTSS at 52 wks. This study was terminated early due to futility. Results The ITT population was mostly female (84.2%), and seropositive (RF and/or anti-CCP, 95%) with a mean age of 53.2 yrs, mean RA diagnosis of 6.8 yrs, and DAS28-CRP of 5.6±1.0 (mean ± SD). At wk 24 in the efficacy population (ITT population excluding pts on <10 mg/wk of MTX, n=997), there were no significant differences among the 120/Q4W, 90/Q2W, and PBO groups in the percentage of pts achieving ACR20 (NRI; 29.7%, 32.8%, 25.1%). There was no significant difference among the 120/Q4W, 90/Q2W, and PBO groups in structural progression defined as change from baseline in mTSS (mean ± SD) at wk 52 (1.5±4.9, 0.9±3.8, 1.7±5.3). A modest difference was observed in wk 24 HAQ-DI results (mean ± SD) in the 90/Q2W group (mBOCF; 1.2±0.6) vs PBO (mBOCF; 1.3±0.7) [p=0.005]; no difference was observed in the 120/Q4W group (mBOCF; 1.3±0.6). After 52 wks, changes in CD3-CD20+ B cells in the 120/Q4W, 90/Q2W, and PBO groups were −15.0%, −18.8%, and 5.3%. Changes in immunoglobulin levels in the 120/Q4W, 90/Q2W, and PBO groups were: IgM (−16.3%, −19.4%, −0.1%), IgA (−11.4%, −4.7%, 1.2%), and IgG (−8.6%, −7.8%, 0.1%). Safety was evaluated in all randomized pts who received ≥1 dose of study treatment (n=1038). Discontinuations due to an AE were similar across the 120/Q4W, 90/Q2W, and PBO groups (4.3%, 3.5%, 2.9%) as were TEAEs (54.2%, 50.7%, 53.7%) and SAEs (5.2%, 5.2%, 4.9%). For the 120/Q4W, 90/Q2W, and PBO groups, there was no difference in reports of AEs of interest: infections (24%, 23%, 26%); injection-site reactions (2.3%, 4.3%, 2.3%); and allergic/hypersensitivity events (4.3%, 3.5%, 4.6%). Three deaths occurred: 2 120/Q4W pts (sepsis, MI) and 1 PBO pt (MI). Conclusions In this phase 3 study, tabalumab demonstrated no clinical efficacy despite evidence of biologic activity. There were no differences in reports of AEs of interest and no new or unexpected safety findings for RA pts receiving tabalumab. Disclosure of Interest J. Smolen Grant/research support: Pfizer, Consultant for: Pfizer, Eli Lilly and Company, M. Weinblatt Consultant for: Eli Lilly and Company, Pfizer, Vertex, D. van der Heijde Consultant for: Eli Lilly and Company, AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi Sankyo Ltd, ...
BackgroundA prospective observational study embedded within the United States (US) Consortium of Rheumatology Researchers of North America Registry was initiated to evaluate the safety and effectiveness of tofacitinib following US Food and Drug Administration (FDA) approval (6Nov2012).ObjectivesTo provide an updated characterisation of the patients prescribed tofacitinib during the early period after US FDA approval.MethodsRheumatoid Arthritis (RA) patients in the Corrona registry initiating tofacitinib through 30Nov2014 were identified. As a comparator, RA patients with no history of tofacitinib use initiating any biologic disease modifying antirheumatic drugs (bDMARD) between 6Nov2012-30Nov2014 were also identified. Patient characteristics at the time of initiation are summarized and compared between groups. Continuous covariates are compared using a rank-sum test; categorical covariates are compared using a chi-square test.ResultsOver the study period, there were 560 RA patients newly prescribed tofacitinib and 3458 newly prescribed bDMARD in the registry. Clinical characteristics are summarized in the Table 1. Tender and swollen joint counts and clinical disease activity index (CDAI) scores were generally similar for tofacitinib and bDMARD initiators, as were the distribution of CDAI scores (i.e. high/moderate/low disease activity and remission). However, tofacitinib initiators had significantly higher health assessment questionnaire (HAQ) scores. In addition, the mean disease duration was significantly longer for initiators of tofacitinib (13.4 yrs) versus bDMARDs (10.2 years, p<0.001). Tofacitinib initiators also had a higher median (IQR) number of prior biologic drugs [tofacitinib 3 (1-4) versus bDMARDs 1 (0-2)]. Use of monotherapy and combination DMARD therapies differed among tofacitinib versus bDMARD users (p<0.001), with monotherapy more commonly used for tofacitinib (46%) versus bDMARD (27%) users.ConclusionsAnalysis of this US-based cohort reflects prescriber patient selection decisions. Overall, tofacitinib and bDMARD initiators were similar with respect to baseline demographics and disease severity. As expected for newer therapies, patients with longerstanding disease and prior bDMARD use were more common among those for whom tofacitinib has been initiated to date compared with those starting a bDMARD during the same time period, although prescribing is not limited to patients with moderate/high disease activity. Monotherapy and combination treatment strategies differed between tofacitinib versus bDMARD treated patients. These factors need to be considered in assessment an assessment of the comparative effectiveness and safety of tofacitinib versus other RA therapies during longitudinal followupAcknowledgementsThis study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.Disclosure of InterestA. Kavanaugh Grant/...
BackgroundClinical studies demonstrated that baseline disease activity including C-reactive protein (CRP) level was a predictor variable for radiographic joint damage in patients with rheumatoid arthritis (RA).ObjectivesTo identify variables associated with radiographic joint damage in patients with RA treated with intravenously administered golimumab (GLM) + Methotrexate (MTX) or MTX + placebo (PBO).MethodsGO-FURTHER was a multicenter, randomized, placebo-controlled study. Adult patients with active RA despite MTX therapy (≥6 tender and swollen joints, CRP ≥1.0 mg/dL, and RF and/or anti-CCP positive) were randomized to placebo (PBO) + MTX or GLM (2mg/kg) plus MTX at week 0, 2, and every 8 week thereafter (GLM group). Patients in PBO group with <10% improvement in tender and swollen joint count from baseline at week 16 entered early escape (EE) and received a 2 mg/kg GLM infusion at weeks 16 and 20 and every 8 weeks subsequent. Radiographic progression was measured using Total Sharp score (TSS). The correlations of TSS with hemoglobin, disease activity score (DAS28-CRP)and physical function evaluated with Health Assessment Questionnaire (HAQ) were assessed using Spearman's correlation or multivariable liner regression model. Anemia was defined based on World Health Organization (WHO) criteria as Hgb <12 g/dl in women and <13 g/dl in men.ResultsModerate to severe RA was demonstrated by a mean DAS28 score of 5.9 with TSS of 48.5 in all patients group at baseline. In linear regression models, baseline DAS28, HAQ score, and Hgb level was correlated with baseline TSS with Spearman's correlation coefficient (r) of 0.148 (p<0.01), 0.0.193 (p<0.001) and -0.129 (p<.001), respectively. Similar correlation relationships of TSS score with DAS28, HAQ and Hgb were observed at Week 24. In multiple linear regression models, after adjusting for effect of other factors, Hgb level demonstrated significant correlation with TSS at the baseline or Week 24. The change in Hgb at Week 20 also was correlated with change in TSS at Week 24 after adjusting for change in DAS28 and HAQ. GLM IV + MTX-treated patients demonstrated less radiographic damage than MTX+PBO-treated patients regardless of their anemia status at baseline or week 20.ConclusionsHemoglobin level is an independent variable predicting radiographic progression in MTX refractory RA patients.Disclosure of InterestR. Westhovens Grant/research support from: Janssen R & D, LLC, C. Han Employee of: Johnson & Johnson Pharmaceutical Services, LLC, M. Weinblatt Grant/research support from: Janssen R & D, LLC, L. Kim Employee of: Janssen R & D, LLC, E. Hsia Employee of: Janssen R & D, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, C. Bingham III Grant/research support from: Janssen R & D, LLC
BackgroundA Treat-to-Target approach (T2T), treating patients with RA towards a target, either remission or low disease activity (T2T-REM or T2T-LDA) is nowadays recommended. However it has never been assessed whether such a strategy in daily clinical practice really leads to more patients meeting that target.MethodsBIODAM is a 2-year prospective cohort including patients in daily practice with RA from 10 countries, who were started or changed on DMARD and/or anti-TNF treatment and were followed-up every 3 months. Participating physicians were required to practice T2T per protocol. Per visit was decided whether a patient was treated according to T2T or not. T2T-REM was considered met: i) if a patient had already a disease activity score below the target (DAS28-CRP<2.6); or ii) if treatment was intensified (by increasing dosage or adding drugs) upon a DAS28≥2.6. T2T-LDA was computed using the benchmark for low disease activity (LDA) (DAS28<3.2) (T2T-LDA). The main outcome was the presence or absence of ACR/EULAR-boolean remission 3 months after T2T-REM or T2T-LDA. Another outcome analysed was sustained remission (present >6 months). The relationship between T2T and ACR/EULAR Boolean remission 3 months later (or sustained remission) was investigated using generalized estimating equations with auto-regression.ResultsIn total 3084 visits of 539 patients (mean (SD) age: 56 (13) years, 76% female, disease duration 6 (8) years). In 68% of the visits, T2T-REM was applied (in 79% of the visits T2T-LDA was applied). ACR/EULAR-boolean remission was reached in 15% of the visits. Appropriate application of T2T-REM led to a 50% higher likelihood of ACR/EULAR-boolean remission 3 months later than not applying T2T-REM. Both T2T-REM and T2T-LDA strategies led to lower disease activity (with an exception of DAS28 remission or DAS28-LDA). Only 9% of the treatment intensifications followed upon a DAS28 between 2.6 and 3.2, and 79% of the intensifications were applied upon a DAS>3.2. Following T2T strategies led to higher achievement of sustained remission (table).ConclusionsA treat-to-target approach, even with a modest benchmark (DAS28 = 3.2), works and leads to a higher achievement of (sustained) ACR/EULAR-remission. Our study illustrates the importance of acting upon the data that is routinely collected in a clinical encounter. Rheumatologists should be encouraged to follow a treat-to-target approach in order to improve the outcome of their patients.Disclosure of InterestNone declared
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.