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Josef S Smolen - One of the best experts on this subject based on the ideXlab platform.

  • radiographic progression based on baseline characteristics from TNF Inhibitor biosimilar studies in patients with rheumatoid arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Josef S Smolen, Mark C. Genovese, Michael E Weinblatt, Paul Emery, Gihyun Myung, Young Mo Kang, Wanhee Yoo, Edward C Keystone, Inyoung Baek, Jeehoon Ghil
    Abstract:

    Objective Phase III clinical trials of the tumour necrosis factor Inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Methods Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson's correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. Results A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson's correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P Conclusions In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. Clinical trial registration numbers EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results.

  • radiographic progression based on baseline characteristics from TNF Inhibitor biosimilar studies in patients with rheumatoid arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Josef S Smolen, Mark C. Genovese, Michael E Weinblatt, Paul Emery, Gihyun Myung, Young Mo Kang, Wanhee Yoo, Edward C Keystone, Inyoung Baek, Jeehoon Ghil
    Abstract:

    Phase III clinical trials of the tumour necrosis factor Inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson’s correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson’s correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001). In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results

  • sat0162 a pooled analysis of 1 year clinical outcomes among 6 month responders and non responders from three randomised controlled studies of TNF Inhibitor biosimilars in patients with rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Josef S Smolen, Michael E Weinblatt, Paul Emery, Jungyoon Choe, Jonathan Kay, Jieun Lee, Gihyun Myung, Hyoryeong Seo, Jeehoon Ghil
    Abstract:

    Background: SB4, SB2, and SB5 are biosimilars of etanercept, infliximab, and adalimumab. Phase III randomised, double-blind studies were conducted to compare efficacy and safety between biosimilars and reference products. Objectives: Assess and compare 1-year outcomes among 6-month responders and non-responders. Methods: Patients who had 6-month data from each phase III study were pooled and categorised, based on their disease status at 6 months (week 24 for etanercept and adalimumab and week 30 for infliximab) and 1 year (week 52 for etanercept and adalimumab and week 54 for infliximab). Responders included patients who achieved an ACR20 response or low disease activity (including remission) by DAS28, SDAI, or CDAI at 6 months. Those who did not or dropped out were considered non-responders. Primary outcome was the proportion of responders who maintained responses from 6 months to 1 year or non-responders at 6 months who achieved responses at 1 year. Results: Data from 1461 patients were included in the analysis. For all treatments combined, 81.1% of ACR20 responders, 69.6%, 77.8%, and 77.0% of responders with DAS28, SDAI, and CDAI low disease activity (LDA) at 6 months maintained their responses at 1 year, and 33.9%, 18.8%, 26.7%, and 24.9% of 6-month non-responders achieved responses at 1 year, respectively. The proportions of patients maintaining or achieving an ACR20 response or DAS28, SDAI, and CDAI LDA at 1 year were similar across different treatment groups (Table 1). Conclusion: A pooled analysis of TNF Inhibitor biosimilars and reference products showed that about 20-30% of responders lost their response, while about 20-30% gained it. Thus, the overall stability of disease fluctuation in our 1-year phase III studies is a consequence of a similar success and failure rate. The validity of these data can be seen by the similarities in these outcomes between different types of TNF-Inhibitors and similarity between biosimilars and respective reference products. References [1] Emery, et al. Rheumatology. 2017 Dec;56(12):2093-2101. [2] Smolen, et al. Ann Rheum Dis. 2018 Feb;77(2):234-240. [3] Weinblatt, et al. Arthritis Rheumatol. 2018 Jan;70(1):40-48. Disclosure of Interests: Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Jung-Yoon Choe: None declared, Jonathan Kay Grant/research support from: Gilead Sciences, Pfizer, UCB Pharma, Consultant for: AbbVie, Boehringer Ingelheim GmbH, Celltrion Healthcare, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals, Pfizer, Samsung Bioepis, Sandoz, UCB Pharma, Jieun Lee Employee of: Samsung Bioepis, Gihyun Myung Employee of: Samsung Bioepis, Hyoryeong Seo Employee of: Samsung Bioepis, Jeehoon Ghil Employee of: Samsung Bioepis

  • golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor α Inhibitors findings with up to five years of treatment in the multicenter randomized double blind placebo controlled phase 3 go after study
    Arthritis Research & Therapy, 2015
    Co-Authors: Josef S Smolen, J Wollenhaupt, Eric L Matteson, Robert Landewe, Stephen Xu, Yiying Zhou, Mittie K Doyle, Norman Gaylis, Frederick T Murphy, Elizabeth C Hsia
    Abstract:

    Introduction The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-α (TNF)-Inhibitor(s).

  • insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti tumour necrosis factor therapy post hoc analyses from the go after study
    Annals of the Rheumatic Diseases, 2014
    Co-Authors: Josef S Smolen, Eric L Matteson, Robert Landewe, Elizabeth C Hsia, Stephen Xu, Yiying Zhou, Mittie K Doyle
    Abstract:

    Objective Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) Inhibitor use. Methods Patients (n=461) previously receiving ≥1 TNF Inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint (≥20% improvement in American College of Rheumatology (ACR20) criteria at week 14) findings have been reported for all patients in the trial. Reported herein are further assessments of efficacy/safety among patients receiving golimumab +methotrexate (MTX). Results Among efficacy-evaluable patients who received MTX at baseline, more receiving golimumab +MTX (n=201) than placebo+MTX (n=103) achieved ACR20 (40.8% vs 14.6%), ACR50 (20.9% vs 3.9%), and ACR70 (11.4% vs 2.9%) responses at week 24. Among the 137 patients who had received only one prior TNF Inhibitor (adalimumab, n=33; etanercept, n=47; and infliximab, n=57), week 24 ACR20 rates were 30.3%, 46.8% and 50.9%, respectively, and thus lowest among those who previously used adalimumab. ACR20 response rates were 44.5% (61/137), 36.2% (17/47) and 23.5% (4/17) among patients who had received one, two or three TNF Inhibitors, respectively. Adverse event (AE) rates were comparable across type/ number of prior anti-TNF agents, but appeared somewhat higher among patients who discontinued previous TNF Inhibitor(s) due to intolerance (37/49, 75.5%) versus lack of efficacy (LOE, 113/191, 59.2%). Conclusions Patients with active RA previously treated with ≥1 TNF Inhibitor had clinically relevant improvement with golimumab+MTX, which appeared somewhat enhanced among those who received only etanercept or infliximab as their prior TNF Inhibitor. Golimumab+MTX safety appeared similar across patients, regardless of TNF Inhibitor(s) previously used, with fewer AEs occurring among patients who discontinued prior therapy for LOE.

Johan Askling - One of the best experts on this subject based on the ideXlab platform.

  • rheumatoid arthritis anti tumour necrosis factor treatment and risk of squamous cell and basal cell skin cancer cohort study based on nationwide prospectively recorded data from sweden
    BMJ, 2016
    Co-Authors: Pauline Raaschou, Julia F Simard, Charlotte Asker Hagelberg, Johan Askling
    Abstract:

    Objective  To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) Inhibitor treatment, and in the general population. Design  Population based cohort study. Setting  Nationwide data from Sweden. Participants  Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF Inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers. Main outcome measure  Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12). Results  For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF Inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF Inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF Inhibitors did not further increase risks. Conclusion  A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF Inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF Inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF Inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF Inhibitors originates from factors other than that treatment.

  • effectiveness of TNF Inhibitor switch in ra results from the national swedish register
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Katerina Chatzidionysiou, Johan Askling, Jonas Eriksson, Lars Erik Kristensen, Ronald F Van Vollenhoven
    Abstract:

    Background Switching to a second tumour necrosis factor Inhibitor (TNFi) after discontinuation of a first in rheumatoid arthritis (RA) is a common strategy. The reason for the switch from the first TNFi could potentially influence the response to therapy. Data on direct comparisons between TNFi after switching are limited. Methods The national Swedish register was used. RA patients who switched to a second TNFi (infliximab, etanercept or adalimumab) after failure of a TNFi as first-ever biologic were identified. Effectiveness of treatment was compared across the three drugs according to the first TNFi used, the reason for discontinuing and the drug survival. Drug survival across TNFi used as second biologic was compared. Results Half of all patients starting infliximab, adalimumab or etanercept during the period 2005–2012 discontinued treatment for various reasons. Of these patients, a third switched within 2 months to a second TNFi (infliximab, etanercept or adalimumab). Around 35% of all patients achieved low disease activity or remission at 6 months. Regarding the switching strategy, best results were observed among patients who switched from infliximab to etanercept because of (secondary) inefficacy. Etanercept as second TNFi was associated with longer drug survival compared with infliximab. Conclusions Switching to a second TNFi after the failure of the first may lead to good clinical results. The inter-drug differences in drug survival on the second TNFi mirror those reported previously for the first TNFi, suggesting that these differences are not solely due to channelling bias.

  • TNF Inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis a nationwide cohort study
    Annals of the Rheumatic Diseases, 2014
    Co-Authors: Pauline Raaschou, Thomas Frisell, Johan Askling
    Abstract:

    Objective To investigate the risk of breast cancer recurrence in rheumatoid arthritis (RA)—patients with tumour necrosis factor Inhibitor (TNFi) treatment and a history of breast cancer, taking several breast cancer, comorbidity and RA-related prognostic factors into account. Methods 143 female TNFi-treated patients (1999–2010) with RA and a history of breast cancer before start of TNFi were identified through register linkages, and matched 1:1 from a cohort of 1598 comparable biologics-naive individuals. 120 TNFi-treated and 120 matched biologics-naive individuals with a history of equally recent/distant breast cancer met the eligibility criteria and comprised the final study population. The primary outcome was first recurrence of breast cancer. Through register-linkages and chart review, individuals were followed until 2011. HRs for recurrence were calculated using Cox regression. Results The median time from breast cancer diagnosis until TNFi-treatment/start of follow-up was 9.4 years. Modest differences in breast cancer characteristics and/or treatment among TNFi-treated and biologics-naive individuals were noted at time of breast cancer diagnosis. Median follow-up from TNFi start was 4.9 years (4.6 years among biologics-naive). Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up, compared with 9 among the matched biologics-naive (16/1000 person-years). The adjusted corresponding HR was 1.1 (95% CI 0.4 to 2.8). Conclusions Among patients with RA and a history of breast cancer, those who started TNFi-treatment did not experience more breast cancer recurrences than patients with RA treated otherwise. The generalisability of our findings to women with a very recent or a poor prognosis of breast cancer remains unknown.

  • rheumatoid arthritis anti tumour necrosis factor therapy and risk of malignant melanoma nationwide population based prospective cohort study from sweden
    BMJ, 2013
    Co-Authors: Pauline Raaschou, Julia F Simard, Marie Holmqvist, Johan Askling
    Abstract:

    Objectives To investigate the potential association between tumour necrosis factor (TNF) Inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF Inhibitors as used in rheumatoid arthritis. Design Population based cohort study. Setting Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n=10 878) or not (n=42 198) with TNF Inhibitors and matched general population comparators (n=162 743). Main outcome measures The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF Inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer. Results 113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF Inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100 000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF Inhibitors compared with those not treated with biological drugs. Conclusion Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF Inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF Inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.

  • small area variations in sales of TNF Inhibitors in sweden between 2000 and 2009
    Scandinavian Journal of Rheumatology, 2011
    Co-Authors: Martin Neovius, Julia F Simard, Johan Askling, Anders Sundstrom, Bjorn Wettermark, Thomas Cars, Nils Feltelius, Lars Klareskog
    Abstract:

    Objective: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) Inhibitors.Methods: For 2000–2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden.Results: From 2000 to 2009, annual TNF Inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7–5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold i...

Paul Emery - One of the best experts on this subject based on the ideXlab platform.

  • interferon related gene expression in response to TNF Inhibitor treatment in ankylosing spondylitis patients a pilot study
    Rheumatology, 2021
    Co-Authors: Stephanie R Harrison, Paul Emery, Agata Burska, Helena Marzoortega, Frederique Ponchel
    Abstract:

    Objective Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the spine and sacroiliac joints. TNF Inhibitor (TNFi) drugs are recommended for patients not responding to NSAIDs; however, there is a significant need for biomarkers of response. IFN-regulated genes (IRGs) and other cytokines/chemokines are linked to autoimmune diseases and have been associated with treatment response. Our objective was to explore whether IRGs and cytokines/chemokines can be associated with response to TNFiagents in AS. Methods Peripheral blood mononuclear cells were obtained from 26 AS patients who were to receive a TNFi (I, n = 15) or placebo (P, n = 11) at week 0 and week 22. Response (R)/non-response (NR) was defined as reduction in ASDAS ≥ 1.2 points or reduction in sacroiliac/vertebral MRI lesions. The expression of 96 genes was quantified using TaqMan assays. Finally, ELISA was used to measure IL-6 in serum samples from another 38 AS patients. Results Analysis of gene expression in 26 baseline samples segregated patients into four groups defined by a signature of 15 genes (mainly IRGs). ASDAS response was associated with one group independently of treatment received. We then analysed response to the TNFi (n = 15) and identified a 12-gene signature associated with MRI response. A third IRG signature was also associated with a reduction in IRGs expression post-TNFi samples (n = 10 pairs). Finally, decreased circulating IL-6 was associated with BASDAI-R. Conclusion This pilot study suggests an association between IRG expression and response to TNFi in AS. These findings require validation in a larger cohort in order to construct predictive algorithms for patient stratification.

  • radiographic progression based on baseline characteristics from TNF Inhibitor biosimilar studies in patients with rheumatoid arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Josef S Smolen, Mark C. Genovese, Michael E Weinblatt, Paul Emery, Gihyun Myung, Young Mo Kang, Wanhee Yoo, Edward C Keystone, Inyoung Baek, Jeehoon Ghil
    Abstract:

    Objective Phase III clinical trials of the tumour necrosis factor Inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Methods Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson's correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. Results A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson's correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P Conclusions In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. Clinical trial registration numbers EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results.

  • radiographic progression based on baseline characteristics from TNF Inhibitor biosimilar studies in patients with rheumatoid arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Josef S Smolen, Mark C. Genovese, Michael E Weinblatt, Paul Emery, Gihyun Myung, Young Mo Kang, Wanhee Yoo, Edward C Keystone, Inyoung Baek, Jeehoon Ghil
    Abstract:

    Phase III clinical trials of the tumour necrosis factor Inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson’s correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson’s correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001). In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results

  • sat0162 a pooled analysis of 1 year clinical outcomes among 6 month responders and non responders from three randomised controlled studies of TNF Inhibitor biosimilars in patients with rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Josef S Smolen, Michael E Weinblatt, Paul Emery, Jungyoon Choe, Jonathan Kay, Jieun Lee, Gihyun Myung, Hyoryeong Seo, Jeehoon Ghil
    Abstract:

    Background: SB4, SB2, and SB5 are biosimilars of etanercept, infliximab, and adalimumab. Phase III randomised, double-blind studies were conducted to compare efficacy and safety between biosimilars and reference products. Objectives: Assess and compare 1-year outcomes among 6-month responders and non-responders. Methods: Patients who had 6-month data from each phase III study were pooled and categorised, based on their disease status at 6 months (week 24 for etanercept and adalimumab and week 30 for infliximab) and 1 year (week 52 for etanercept and adalimumab and week 54 for infliximab). Responders included patients who achieved an ACR20 response or low disease activity (including remission) by DAS28, SDAI, or CDAI at 6 months. Those who did not or dropped out were considered non-responders. Primary outcome was the proportion of responders who maintained responses from 6 months to 1 year or non-responders at 6 months who achieved responses at 1 year. Results: Data from 1461 patients were included in the analysis. For all treatments combined, 81.1% of ACR20 responders, 69.6%, 77.8%, and 77.0% of responders with DAS28, SDAI, and CDAI low disease activity (LDA) at 6 months maintained their responses at 1 year, and 33.9%, 18.8%, 26.7%, and 24.9% of 6-month non-responders achieved responses at 1 year, respectively. The proportions of patients maintaining or achieving an ACR20 response or DAS28, SDAI, and CDAI LDA at 1 year were similar across different treatment groups (Table 1). Conclusion: A pooled analysis of TNF Inhibitor biosimilars and reference products showed that about 20-30% of responders lost their response, while about 20-30% gained it. Thus, the overall stability of disease fluctuation in our 1-year phase III studies is a consequence of a similar success and failure rate. The validity of these data can be seen by the similarities in these outcomes between different types of TNF-Inhibitors and similarity between biosimilars and respective reference products. References [1] Emery, et al. Rheumatology. 2017 Dec;56(12):2093-2101. [2] Smolen, et al. Ann Rheum Dis. 2018 Feb;77(2):234-240. [3] Weinblatt, et al. Arthritis Rheumatol. 2018 Jan;70(1):40-48. Disclosure of Interests: Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Jung-Yoon Choe: None declared, Jonathan Kay Grant/research support from: Gilead Sciences, Pfizer, UCB Pharma, Consultant for: AbbVie, Boehringer Ingelheim GmbH, Celltrion Healthcare, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals, Pfizer, Samsung Bioepis, Sandoz, UCB Pharma, Jieun Lee Employee of: Samsung Bioepis, Gihyun Myung Employee of: Samsung Bioepis, Hyoryeong Seo Employee of: Samsung Bioepis, Jeehoon Ghil Employee of: Samsung Bioepis

  • ab0460 long term drug survival of etanercept vs other TNF Inhibitor therapies in patients with rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Paul Emery, Bonnie Vlahos, Piotr Szczypa, M Thakur, H Jones, John Woolcott, P Santos V Estrella, Allan Gibofsky, Catherine Rolland, Gustavo Citera
    Abstract:

    Background TNFα Inhibitors have profoundly altered outcomes for patients with rheumatoid arthritis (RA) since they were introduced >15 years ago, by reducing disease activity and radiographic progression and improving quality of life. As a chronic disease, RA often requires life-long treatment, understanding drug survival in real-world settings can be beneficial in optimising disease management. Objectives To compare the long-term drug survival of adalimumab (ADA), certolizumab pegol (CZP), etanercept (ETN), golimumab (GLM), and infliximab (IFX) in patients with RA based on systematic literature review (SLR). Methods In this SLR, the goal was to identify full-text articles containing registry data or systematic reviews on TNFα Inhibitors, following Cochrane dual-reviewer methodology. Searches were conducted in November 2017 with no date restriction, using Embase®, MEDLINE®, the Cochrane Central Trials Register and Database of Systematic Reviews, other Cochrane Library databases, and PubMed. Outcomes extracted included drug survival data that were analysed and reported using Kaplan-Meyer or Cox regression methods. Results Of 3688 non-duplicated publications initially identified, 3299 were excluded based on titles or abstracts and 344 based on full-text screening, leaving 26 publications published between 2005 and 2017 included in the analysis. The number of studies (range of sample size) for each drug were ADA: 15 (25–2349), ETN: 17 (20–3892), IFX: 21 (26–2898), GLM: 4 (2–88) and CZP: 1 (N/A). Among the analysed studies, the mean disease duration in years (range) was ADA: 10.7 (8.2–15.1); ETN: 15.9 (5.0–18.5); IFX: 14.2 (8.5–19.3); CZP: 10.3 (N/A); GLM: 8.9 (8.1–11.5) and mean baseline DAS28 (range) was ADA: 5.0 (4.2–5.9), ETN: 5.2 (4.3–6.3), IFX: 5.3 (4.1–6.4); CZP: 4.7 (N/A) and GLM: 4.7 (4.1–5.1). Trends for survival rates of first-line ETN were slightly higher than ADA at time points≥36 months; ADA and ETN had higher survival rates than IFX at >48 months (figure 1). Conclusions Long-term survival rates for ADA, ETN, and IFX were similar and relatively high for treatment periods up to 36 months. After 36 months, there was a noticeable decline in drug survival for all three TNFα Inhibitors. Heterogeneity in study size and design may contribute to the range of survival data for each agent. Disclosure of Interest P. Emery Consultant for: Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, P. Szczypa Shareholder of: Pfizer, Employee of: Pfizer, M. Thakur Shareholder of: Pfizer, Employee of: Pfizer, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, J. Woolcott Shareholder of: Pfizer, Employee of: Pfizer, P. Santos Estrella: None declared, A. Gibofsky Shareholder of: AbbVie, Angen, Celgene, Pfizer, GSK, J and J, Regeneron, Consultant for: AbbVie, Celgene, MSD, Pfizer, Iroko, Horizon, Samumed, Relburn, Sandoz, Speakers bureau: Amgen, AbbVie, Pfizer, Celgene, Iroko, Horizon, MSD, Novartis, C. Rolland Employee of: Envision Pharma Group, G. Citera Consultant for: Pfizer, AbbVie, Bristol Myers Squibb, Novartis, Roche, L. Marshall Shareholder of: Pfizer, Employee of: Pfizer

Dan Nordstrom - One of the best experts on this subject based on the ideXlab platform.

  • retention and response rates in 14 261 psa patients starting TNF Inhibitor treatment results from 12 countries in eurospa
    Rheumatology, 2020
    Co-Authors: Cecilie Heegaard Brahe, Dan Nordstrom, Lykke Midtboll Ornbjerg, Lennart T H Jacobsson, Michael John Nissen, Eirik Kristianslund, Herman Mann, Maria Jose Santos, Juan Gomez Reino, Ziga Rotar
    Abstract:

    OBJECTIVE To investigate TNF Inhibitor (TNFi) retention and response rates in European biologic-naive patients with PsA. METHODS Prospectively collected data on PsA patients in routine care from 12 European registries were pooled. Heterogeneity in baseline characteristics between registries were explored (analysis of variance and pairwise comparison). Retention rates (Kaplan-Meier), clinical remission [28-joint count DAS (DAS28) <2.6; 28 joint Disease Activity index for Psoriatic Arthritis ⩽4] and ACR criteria for 20% improvement (ACR20)/ACR50/ACR70 were calculated, including LUNDEX adjustment. RESULTS Overall, 14 261 patients with PsA initiated a first TNFi. Considerable heterogeneity of baseline characteristics between registries was observed. The median 12-month retention rate (95% CI) was 77% (76, 78%), ranging from 68 to 90% across registries. Overall, DAS28/28 joint Disease Activity index for Psoriatic Arthritis remission rates at 6 months were 56%/27% (LUNDEX: 45%/22%). Six-month ACR20/50/70 responses were 53%/38%/22%, respectively. In patients initiating a first TNFi after 2009 with registered fulfilment of ClASsification for Psoriatic ARthritis (CASPAR) criteria (n = 1980) or registered one or more swollen joint at baseline (n = 5803), the retention rates and response rates were similar to those found overall. CONCLUSION Approximately half of >14 000 patients with PsA who initiated first TNFi treatment in routine care were in DAS28 remission after 6 months, and three-quarters were still on the drug after 1 year. Considerable heterogeneity in baseline characteristics and outcomes across registries was observed. The feasibility of creating a large European database of PsA patients treated in routine care was demonstrated, offering unique opportunities for research with real-world data.

  • effectiveness and drug survival of TNF Inhibitors in the treatment of ankylosing spondylitis a prospective cohort study
    The Journal of Rheumatology, 2015
    Co-Authors: Arto V. Heinonen, Marja Pertovaara, M. Romu, Hanna E. Hirvonen, A. Similä, Marja Blom, Jaakko Lahteenmaki, Jaana Joensuu, K J Aaltonen, Dan Nordstrom
    Abstract:

    Objective. The aim of this research was to describe the effectiveness and drug survival of tumor necrosis factor (TNF) Inhibitors in the treatment of ankylosing spondylitis (AS) and to analyze the effect of concomitant treatment with conventional disease-modifying antirheumatic drugs. Methods. Patients with AS identified from the National Register for Biologic Treatment in Finland starting their first TNF Inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline Bath AS Disease Activity Index (BASDAI) score. Treatment response and 2-year drug survival were modeled with logistic regression and time-dependent Cox proportional hazard models, respectively. Results. The study comprised 543 patients, of whom 123 also commenced a second TNF Inhibitor during the followup. Treatment was discontinued within 24 months by 25% and 28% of the users of the first and the second TNF Inhibitors, respectively. BASDAI response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF Inhibitors, respectively. Etanercept (ETN; HR 0.42, 95% CI 0.29–0.62) and adalimumab (ADA; HR 0.48, 95% CI 0.30–0.77) were associated with better drug survival in comparison to infliximab (IFX). Also, concurrent use of sulfasalazine (SSZ; HR 0.70, 95% CI 0.49–0.99) decreased the hazard for treatment discontinuation. Conclusion. TNF Inhibitors are equipotent in the treatment of AS; however, ETN and ADA were found superior to IFX in drug survival. The use of SSZ improves treatment continuation.

Cecilie Heegaard Brahe - One of the best experts on this subject based on the ideXlab platform.

  • retention and response rates in 14 261 psa patients starting TNF Inhibitor treatment results from 12 countries in eurospa
    Rheumatology, 2020
    Co-Authors: Cecilie Heegaard Brahe, Dan Nordstrom, Lykke Midtboll Ornbjerg, Lennart T H Jacobsson, Michael John Nissen, Eirik Kristianslund, Herman Mann, Maria Jose Santos, Juan Gomez Reino, Ziga Rotar
    Abstract:

    OBJECTIVE To investigate TNF Inhibitor (TNFi) retention and response rates in European biologic-naive patients with PsA. METHODS Prospectively collected data on PsA patients in routine care from 12 European registries were pooled. Heterogeneity in baseline characteristics between registries were explored (analysis of variance and pairwise comparison). Retention rates (Kaplan-Meier), clinical remission [28-joint count DAS (DAS28) <2.6; 28 joint Disease Activity index for Psoriatic Arthritis ⩽4] and ACR criteria for 20% improvement (ACR20)/ACR50/ACR70 were calculated, including LUNDEX adjustment. RESULTS Overall, 14 261 patients with PsA initiated a first TNFi. Considerable heterogeneity of baseline characteristics between registries was observed. The median 12-month retention rate (95% CI) was 77% (76, 78%), ranging from 68 to 90% across registries. Overall, DAS28/28 joint Disease Activity index for Psoriatic Arthritis remission rates at 6 months were 56%/27% (LUNDEX: 45%/22%). Six-month ACR20/50/70 responses were 53%/38%/22%, respectively. In patients initiating a first TNFi after 2009 with registered fulfilment of ClASsification for Psoriatic ARthritis (CASPAR) criteria (n = 1980) or registered one or more swollen joint at baseline (n = 5803), the retention rates and response rates were similar to those found overall. CONCLUSION Approximately half of >14 000 patients with PsA who initiated first TNFi treatment in routine care were in DAS28 remission after 6 months, and three-quarters were still on the drug after 1 year. Considerable heterogeneity in baseline characteristics and outcomes across registries was observed. The feasibility of creating a large European database of PsA patients treated in routine care was demonstrated, offering unique opportunities for research with real-world data.

  • dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in routine care 2 year outcomes and predictors
    Rheumatology, 2019
    Co-Authors: Cecilie Heegaard Brahe, Simon Krabbe, Mikkel Ostergaard, Lykke Midtboll Ornbjerg, Daniel Glinatsi, H Rogind, Hanne S Jensen, Annette Hansen, Jesper Norregaard, Soren Jacobsen
    Abstract:

    Objectives A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients (91% receiving TNF Inhibitor and 9% a non-TNF Inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation. Conclusion By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.