Katerina Chatzidionysiou

Karolinska Institutet, Сольна, Stockholm, Sweden

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Publications (24)205.56 Total impact

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    ABSTRACT: Objectives Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX). Methods In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) ≥2.6 or a change in DAS28 (ΔDAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28. Results 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with ≥1 ΔDAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005). Conclusions In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission. Trial registration number NCT00808509.
    Preview · Article · Jan 2016
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    ABSTRACT: Objective. To compare the effectiveness of biologics after rituximab (RTX) treatment in RA. Methods. The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries for the Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6 months or less prior to the new biologic and had a baseline visit within 21 days of starting the new biologic. Results. Two hundred and sixty-five patients were analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs 14%, P < 0.001). The HAQ disability index improved in all treatment groups (P < 0.001), but did not differ between biologics, as did drug retention rates. The reasons for discontinuation of RTX and the number of previous biologics had no influence on outcomes. Conclusion. In this observational cohort of patients who discontinued RTX, TCZ provided a better control of RA than ABA or TNFi.
    No preview · Article · Aug 2015 · Rheumatology (Oxford, England)
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    ABSTRACT: Evidence regarding the efficacy and effectiveness of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients who have failed to respond to treatment with a tumour necrosis factor inhibitor (TNFi) is limited. The aim of this study was to describe the effectiveness and survival-on-drug of CZP in a real-life setting, both in TNFi-naïve patients and in patients who had previously failed TNFis, and in relation to disease activity at baseline. The national Swedish Rheumatology Quality Register (SRQ) was used to identify patients with RA starting treatment with CZP between 2009 and 2013. The effectiveness of treatment was assessed using the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), measures of remission, the European League Against Rheumatism (EULAR) response during 0-6 months from start of treatment, and survival-on-drug during the first 30 months. A total of 945 RA patients started treatment with CZP. Of these, 540 (57.1%) received CZP as the first biological treatment, 215 (23%) had failed one previous TNFi, and 190 (20%) had failed at least two TNFis. Overall, 71% achieved at least a EULAR moderate response and 38% had a EULAR good response at 6 months from baseline. TNFi-naïve patients achieved significantly better results and had better survival-on-drug compared to patients who had failed previous TNFis. Around 20% of patients who had not responded to two or more prior TNFis achieved EULAR good response to therapy and a similar percentage achieved remission. Patients who had high baseline disease activity had a higher risk of discontinuing treatment compared to those without high disease activity. In this real-life RA cohort, CZP was associated with significant clinical improvement. The effectiveness and survival-on-drug vary markedly depending on the line of treatment.
    No preview · Article · Jun 2015 · Scandinavian journal of rheumatology
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    ABSTRACT: Background Smoking is a negative predictor of response to antirheumatic therapy. Objectives To assess whether smoking influence the response to rituximab (RTX) in Rheumatoid Arthritis (RA). Methods Pooled data from the Collaborating European Registries for RTX in RA (CERERRA) were used. Patients who received at least 1 cycle with RTX were included. Smoking status was defined as smokers (current smokers) and non-smokers (never and ex-smokers). Analysis of co-variance (ANCOVA) was performed with DeltaDAS28 at 6 months as the dependent variable and smoking status as well as other baseline variables (age, sex, disease duration, number of prior biologic DMARDs) as covariates. Separate analyses were made for anti-CCP positive and negative patients. Results A total of 2274 patients were included - 1815 (80%) non-smokers and 459 (20%) smokers. 81% were female and 80% (out of 1199 patients with available anti-CCP) were anti-CCP positive. Smokers had shorter disease duration than non-smokers (median (IQR) 8 (4-13) years vs. 10 (5-16), p<0.0001), higher number of prior biologic DMARDs (median (IQR) 1 (0-2) vs. 1 (0-1), p<0.0001) and lower DAS28 at baseline (5.3±1.6 vs. 5.8±1.5, p<0.0001). Smokers had less improvement in disease activity than non-smokers at 6 months (mean ± SD DeltaDAS28 -1.5±1.7 vs. -1.8±1.7, respectively, p=0.04). However, the difference was no longer significant after adjustment for baseline differences (p=0.40). When the analysis was stratified by anti-CCP status, smoking did not influence the response to therapy in the anti-CCP negative subset (p=0.39) but there was a trend in the anti-CCP positive subset (p=0.06, figure 1). For the anti-CCP negative patients, 67% of non-smokers and 69% of smokers achieved EULAR response (p=0.6), while in the anti-CCP positive the respective response rates were 76% among non-smokers and 70% among smokers (p=0.09). Conclusions Smoking was negatively associated with the response to rituximab therapy in RA patients who were anti-CCP positive. References Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie: None declared, E. Nasonov: None declared, G. Lukina: None declared, M. Hetland: None declared, E. Hauge: None declared, K. Pavelka Consultant for: MSD, AbbVie, Pfizer, Roche, BMS, C. Gabay Grant/research support from: Roche, Merck, Abbvie, Consultant for: Roche, Abbvie, Pfizer, BMS, Sanofi-Aventis, Merck, AB2 Bio, D. Nordström Consultant for: AbbVie, BMS, MSD, Pfizer, Roche, UCB, H. Canhão: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, S. Saevarsdottir: None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: To compare the effectiveness of biologics after rituximab (RTX) treatment in RA. The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries for the Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6 months or less prior to the new biologic and had a baseline visit within 21 days of starting the new biologic. Two hundred and sixty-five patients were analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs 14%, P < 0.001). The HAQ disability index improved in all treatment groups (P < 0.001), but did not differ between biologics, as did drug retention rates. The reasons for discontinuation of RTX and the number of previous biologics had no influence on outcomes. In this observational cohort of patients who discontinued RTX, TCZ provided a better control of RA than ABA or TNFi. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Clinical trials have shown that tocilizumab (TCZ) is efficacious as monotherapy and in combination with methotrexate (MTX) or other DMARDs. However, longitudinal TCZ retention data from large registry populations have been missing. Objectives To examine retention of TCZ administered alone or in combination with DMARDs in rheumatoid arthritis (RA) patients included in the TOcilizumab Collaboration of European Registries in RA (TOCERRA). Methods RA patients treated with TCZ who had baseline (BL) data and not immediately lost to follow-up were included. Patients were considered as taking TCZ in monotherapy (mono) or combination with DMARDs (combo) based on their BL DMARD co-therapy. Time on TCZ was defined by the time between TCZ start and discontinuation with censoring occurring at date of last visit on TCZ. Crude median TCZ retention with 95% CIs were estimated for mono and combo therapy. The hazard for TCZ discontinuation was modeled using a country-stratified, covariate-adjusted Cox proportional hazards model applied to patients with complete BL covariate information for sex, age, disease duration, number of prior biologics, corticosteroid use, seropositivity (rheumatoid factor or anti-CCP), DAS28, HAQ, and therapy. Results A total of 1271 eligible treatment courses (TCs) were retrieved from 8 registries by April 2013. Of these, 328 (26%) were started as mono and 943 as combo therapy. For 83% of TCs, DMARD co-therapy was stable over time. In 471 TCs (37%) (of which 124 mono) TCZ was discontinued. Main causes of discontinuation were lack of effectiveness (52% for both therapies) or safety issues (34% and 26% for mono and combo). Crude median TCZ retention was 2.2 years (95% CI: 1.7-3) for mono and 3.5 years (95% CI: 2.7-NA) for combo, (P=0.08). Of the 1271 TCs 856 were included in the country-stratified, covariate-adjusted analysis. Significant results were obtained for seropositivity (HR: 0.64 (pos vs neg), 95% CI: (0.49, 0.84), P=0.001) and HAQ (HR: 1.25 (per unit increase), 95% CI: (1.04, 1.49), P=0.014) at BL. Therapy was not significant (HR: 1.16 (mono vs combo), 95% CI: (0.89, 1.52), P=0.27). Conclusions In routine care, TCZ retention is better in patients who are seropositive and have lower HAQ at BL, but comparable for mono and combo therapy. Disclosure of Interest C. Gabay Grant/research support: Roche, M. Riek: None declared, M. Hetland Grant/research support: Roche, E. Hauge Grant/research support: Roche, K. Pavelka Grant/research support: Roche, M. Tomsic Grant/research support: Roche, H. Canhao Grant/research support: Roche, K. Chatzidionysiou Grant/research support: Roche, R. van Vollenhoven Grant/research support: Roche, G. Lukina Grant/research support: Roche, D. Nordström Grant/research support: Roche, E. Lie Grant/research support: Roche, I. Ancuta Grant/research support: Roche, E. Loza Santamaria Grant/research support: Roche, P. van Riel Grant/research support: Roche, T. Kvien Grant/research support: Roche DOI 10.1136/annrheumdis-2014-eular.2806
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background The data on how to optimally retreat patients with RA with rituximab (RTX) have been limited so far. Objectives The aim of this analysis was to compare two common retreatment strategies: A fixed retreatment approach and retreatment when a flare occurs. Methods Pooled data from the Collaborating European Registries for Rituximab in RA (CERERRA) project were used. We identified RA patients who had received at least 2 retreatments (3 courses) with RTX and who had available information about the strategy for retreatment (according to the physician's opinion). The two retreatment strategies were compared by applying an adjusted mixed model analysis with DAS28 improvement as the dependent variable. Results A total of 800 patients were retreated at least twice: 616 patients retreated because of a flare (442 at 1st and 174 at 2nd retreatment) and 184 receiving fixed retreatment (128 at 1st and 56 at 2nd retreatment). Baseline characteristics (incl. age, sex, seropositivity, disease duration, number of prior DMARDs and biologics) at first course of RTX did not differ significantly between the two groups. However, patients retreated on flare had, as expected, a significantly higher DAS28-ESR at the time of 1st retreatment (5.1±1.3 vs. 4.1±1.4, p<0.0001), and a higher HAQ (1.5±0.7 vs. 1.3±0.8, p=0.001). They had also a slightly higher baseline (at the time of RTX start) DAS28 (6.3±1.0 vs. 6.1±1.2, p=0.03). Those retreated on flare were more likely to be treated with corticosteroids (58% vs. 46%, p=0.01) but less likely to receive concomitant DMARDs (82% vs. 92%, p=0.005). The baseline (=start of each cycle) deltaDAS28 (compared to the DAS28 at the time of RTX start) for the two groups is shown in figure 1. Patients receiving fixed retreatment had a significantly higher (in absolute number) deltaDAS28 (p<0.0001) at the start of each cycle, compared to those retreated on-flare. In the adjusted mixed model analysis, we compared the two retreatment groups for the 1st and the 2nd retreatment separately using estimated marginal means. For the 1st retreatment a fixed retreatment yielded significantly better results than the “on-flare”: mean deltaDAS28=-2.4 (95% CI: -3.0; -1.7) vs. -1.8 (95% CI: -3.6; -0.03), p<0.0001. Similar results were found for the 2nd retreatment: mean deltaDAS28=-2.6 (95% CI: -3.1; -2.2) vs. -1.6 (95% CI: -1.8; -1.4), p<0.0001. Conclusions A fixed RTX retreatment strategy in RA seems to be more effective than the retreatment “on-flare” strategy. Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie: None declared, E. Nasonov: None declared, G. Lukina: None declared, M. Hetland: None declared, U. Tarp: None declared, K. Pavelka: None declared, C. Gabay: None declared, D. Nordström: None declared, H. Canhão: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien Grant/research support: research funding to the Diakonhjemmet Hospital from AbbVie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche and UCB, Consultant for: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, R. van Vollenhoven: None declared DOI 10.1136/annrheumdis-2014-eular.2571
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Retreatment with rituximab (RTX) is common clinical practice, although several aspects regarding retreatment, such as frequency, need to be further elucidated. Objectives The aim of this study was to describe the effectiveness of repeated courses of RTX in a large observational cohort of real-life patients with RA. Methods Pooled data from the Collaborating European Registries for Rituximab in RA (CERERRA) project were used. Patients with RA who received at least 4 cycles with RTX were identified and included in the analysis. A covariate-adjusted mixed effects model was fitted to the longitudinal DAS28 for patients with complete covariate information, including country, sex, age, anti-CCP status, number of prior biologics and concomitant DMARD treatment. Results 340 patients met the eligibility criteria for these analyses. At baseline (start of RTX) the mean (SD) age was 53.5 (12.6) years, mean (SD) disease duration 12.1 (8.2) years, 83% were females, 79% RF positive and 74% anti-CCP positive. 60% were treated with corticosteroids and 84% with concomitant DMARD. Patients had failed 2.7 (1.5) prior synthetic DMARDs and 1.1 (1.0) prior biologic DMARDs. The baseline DAS28 was 6.0 (1.4). The mean fixed predicted decrease of DAS28 after the first cycle and after each retreatment (1st, 2nd and 3rd) is shown in figure 1. Significant improvement in DAS28 (p<0.001) was observed for each course of RTX. Comparison between curves (based on estimated marginal means) revealed significant difference between all curves except between 3rd and 4th treatment cycle, suggesting that a more stable DAS28 is achieved after 2nd retreatment. Conclusions Repeated retreatment with RTX can lead to further clinical improvement after the first course of RTX. A trend for stabilization of disease activity score was observed after the 2nd retreatment. Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie Consultant for: AbbVie, BMS, Hospira, Pfizer, UCB, Speakers bureau: AbbVie, BMS, Pfizer, Roche, UCB, E. Nasonov Grant/research support: Roche, G. Lukina Grant/research support: Roche, M. Hetland Speakers bureau: AbbVie, BMS, MSD, Pfizer, U. Tarp: None declared, K. Pavelka: None declared, C. Gabay Consultant for: Roche, D. Nordström Grant/research support: Roche, H. Canhão: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien Grant/research support: to the Diakonhjemmet Hospital from AbbVie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche and UCB, Consultant for: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, Speakers bureau: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, R. van Vollenhoven Grant/research support: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex DOI 10.1136/annrheumdis-2014-eular.2584
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    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.
    No preview · Article · Apr 2014 · Annals of the Rheumatic Diseases
  • K. Chatzidionysiou · R. van Vollenhoven
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    ABSTRACT: Background Certolizumab pegol (Cimzia) is a pegylated TNF inhibitor approved for the treatment of RA. Its efficacy and safety are well established from clinical trials. Objectives To evaluate and describe the efficacy and drug survival of certolizumab pegol in real-life patients. Methods Data from the national registry ARTIS were used for this analysis. Patients with RA, who started treatment with certolizumab pegol were identified. Clinical response was assessed by DAS28 and HAQ improvement as well as EULAR response criteria. Results During the period from Nov 1st, 2009 until September 29th 2011, a total of 196 patients with a diagnosis of RA started treatment with certolizumab pegol. The mean (SD) age and disease duration of the patients was 56.8 (12.7) and 11.9 (10.3), respectively. 80.1% of patients were RF positive, 72.4% were female and 61.7% had concomitant DMARDs. All patients had failed conventional DMARDs and the majority had failed at least one prior biologic. Significant reductions (mean±SD) of DAS28 from baseline (4.9±1.3, N=166) to 3 months (3.8±1.5, N=84) and 6 months (3.5±1.5, N=58) were observed (p<0.0001). Similarly HAQ was reduced from 1.2±0.7 at baseline, to 1.0±0.7 at 3 and remained stable at 6 months (p=0.002). At 3 months the percentages of EULAR Good/Moderate/No responders were 23.8/61.9/14.3% [N patients=84], and at 6 months 25.9/55.2/19% [N patients=58]. 27.4% and 31% of patients achieved DAS28<2.6 at 3 and 6 months, respectively. During the follow-up period 32 patients (16.3%) discontinued treatment with certolizumab pegol: 15 because of lack of efficacy, 7 because of intolerance and 10 for unknown reasons. The mean (SD) time to discontinuation was 3.2 (1.8) months. 20 patients discontinued certolizumab pegol during the first 3 months. In figure 1 the drug survival of certolizumab pegol is shown. Conclusions In this observational cohort of RA patients with long-standing and refractory disease who were treated with certolizumab pegol, 80% achieved a EULAR Good/Moderate response, and about one fourth achieved a EULAR Good response and/or a DAS28<2.6. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background The approved dose of RTX in RA is 1000mg x2, but some data have suggested similar clinical efficacy with 500mg x2. Objectives The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course. Methods Ten European registries submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Efficacy of treatment and retreatment was assessed based on DAS28 reductions and EULAR responses after 6 months. Results Data on RTX dose were available for 2873 out of 3266 patients in CERERRA. 2625 (91.4%) and 248 (8.6%) patients received 1000mg x2 and 500mg x2, respectively. Patients who were treated with 500 mg x2 were significantly older (mean±SD: 55.2±15.8 vs. 52.6±12.6, yrs, p=0.002), had longer disease duration (13.6±11.9 vs. 10.9±8.2, yrs, p<0.0001), higher number of prior DMARDs (2.6±1.3 vs. 2.4±1.4, p=0.04) but lower number of prior biologics (0.7±0.9 vs. 1.0±1.0, p<0.0001) and lower baseline DAS28 (5.7±1.3 vs. 5.9±1.3, p=0.02) than those treated with 1000 mg x2. Additionally they were less likely to receive concomitant DMARDs (72.6% vs. 83.1%, p<0.0001) but more likely to receive concomitant corticosteroids (65.7% vs. 59.3%, p=0.03). Both dosages lead to significant clinical outcomes at 6 months. Patients with the higher dose (1000mg x2) achieved numerically slightly greater DAS28 reductions at 6 months compared to those treated with the lower dose (500mg x2) (mean DeltaDAS28±SD =1.8±1.3 vs. 1.5±1.5, p=0.3 corrected for baseline DAS28 0.07). Similar percentages of patients achieved EULAR good response (45.3% vs. 48%, p=0.3) and remission (9.4% vs. 13.9%, p=0.2) in the 1000 mg x2 and 500 mg x2 groups, respectively. At 6±1.5 months 579 patients received retreatment with 1000 x2 mg RTX and 26 patients with 500 mg x2. Patients who received different dose at retreatment that at first treatment, as well as patients who were retreated at different time points during the first year, were disregarded from the analysis. Retreatment with 1000 mg x2 led to even greater DAS28 reductions at 12 than at 6 months (DeltaDAS28 6m =1.94±1.06, DeltaDAS28 12m =2.84±1.46, p by paired t-test <0.0001), while retreatment with 500 mg x2 led to no significant further DAS28 reduction (6m =1.15±1.58, 12m =0.87±1.63, p=0.5). A significantly higher good responders rate was observed for the higher dose of RTX for the retreated patients (82% vs. 16.7%, p=0.001). Conclusions In this large observational cohort initial treatment with RTX at 500 mg x2 and 1000 mg x2, led to comparable clinical outcomes. The higher dose but not the lower dose was associated with further DAS28 reductions when given as a second treatment course. Disclosure of Interest None Declared
    Full-text · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: 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. 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. 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. 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.
    No preview · Article · Jan 2014 · Annals of the rheumatic diseases
  • Ronald F van Vollenhoven · Katerina Chatzidionysiou
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    ABSTRACT: Since the 1990s, patients with rheumatoid arthritis have been treated with at least one DMARD. Methotrexate, which is usually the first-line treatment, elicits good or even excellent clinical results in 20–30% of patients—but in most patients it does not. Thus, an important question is what to do after methotrexate failure.
    No preview · Article · Jul 2013 · Nature Reviews Rheumatology
  • Katerina Chatzidionysiou · Ronald van Vollenhoven

    No preview · Article · May 2013 · Clinical Practice
  • K Chatzidionysiou · RF van Vollenhoven
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    ABSTRACT: Objective: The purpose of this study was to characterize and compare responses in patients who had failed one tumour necrosis factor (TNF) inhibitor when switching to another TNF inhibitor or rituximab (RTX). Methods: The Stockholm TNF follow-up registry (STURE) was used. Treatment results at 6 months were analysed by (i) the biologic used, (ii) the type of anti-TNF switch, and (iii) the reason for discontinuation (inefficacy or intolerance). Results: A total of 328 patients who failed an anti-TNF switched to an alternative biologic, 69 to RTX, 161 to an anti-TNF monoclonal antibody (mAb), and 98 to etanercept (ETA). Significant reductions in the 28-joint Disease Activity Score (DAS28) at 6 months were observed for all groups. The mean ± SD reduction in DAS28 was 1.70 ± 1.18 for RTX, 1.40 ± 1.51 for ETA, and 0.67 ± 1.36 for mAb, the difference being statistically significant between RTX and mAb (p < 0.0001). For patients who had failed ETA, RTX led to significantly greater DAS28 reductions than mAb (p = 0.01). When the reason for discontinuation of the previous anti-TNF was intolerance or secondary inefficacy, RTX led to significantly greater DAS28 reduction compared to mAb and ETA (p = 0.01 and p = 0.03, respectively). Conclusions: In this observational cohort, patients who failed one anti-TNF had better overall results when treated with RTX than with a subsequent anti-TNF mAb. Having failed ETA, RTX yielded greater DAS28 reductions and European League Against Rheumatism (EULAR) responses than mAb. The advantage of RTX was most clearly seen in patients who had failed anti-TNF because of intolerance or secondary inefficacy.
    No preview · Article · Jan 2013 · Scandinavian journal of rheumatology
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    ABSTRACT: Background Predictors of response to biologic therapy in rheumatoid arthritis (RA) are needed to achieve a more individualized therapy. Seropositivity has been associated with better response to rituximab (RTX). Objectives To assess the 6-month response to the first RTX course in RA according to RF and ACPA status. Methods Ten European registries submitted anonymized datasets from RA patients who had started RTX, and datasets were pooled and analysed. Chi-square test for comparison of categorical variables and t-test for continuous data were used. Predictors of response were identified by logistic regression analysis. Results 3266 patients were included in the cohort. 79.9% of patients were RF (+) (2041 out of 2553) and 73.2% were ACPA (+) (877 out of 1198). 718 patients were double positive (DP) and 147 double negative (DN). 2200 patients were RF (+) and/or ACPA (+). Improvements of DAS28 (ΔDAS28) at 6 months were significantly better for RF (+) than RF (–) patients as well as for ACPA (+) than ACPA (–), DP vs. DN and RF and/or ACPA (+) vs. DN (table 1). A significantly higher percentage of ACPA (+) and DP patients achieved EULAR Good Response at 6 months compared to ACPA (–) and DN, respectively (table 1). The completeness of data was very similar for seropositive and seronegative patients, with the percentage of missing data at 6 months being approximately 50% in all groups. A significantly higher percentage of seronegative patients received retreatment by 6 months than seropositive patients. In univariate analyses adjusted for age and gender ACPA positivity (OR=2.03, p=0.016) and DP (OR=2.43, p=0.03) but not RF positivity (OR=1.53, p=0.07) predicted EULAR good response to therapy with RTX at 6 months after the first treatment. Conclusions In this large observational cohort of RA patients treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months compared to seronegative patients. Baseline ACPA positivity may be a better predictor for good response to RTX than RF positivity. Disclosure of Interest None Declared
    No preview · Article · Jun 2012 · Annals of the Rheumatic Diseases
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    ABSTRACT: Analysis of the Swedish Farmacotherapy (Swefot) trial at 12 months showed that the addition of an anti-tumour-necrosis-factor agent gave an improved clinical outcome compared with the addition of conventional disease-modifying antirheumatic drugs in patients with methotrexate-refractory early rheumatoid arthritis. Here we report the 2 year follow-up assessment. In this randomised, non-blinded, parallel-group trial, we enrolled adult patients older than 18 years with rheumatoid arthritis and a symptom duration of less than 1 year from 15 rheumatology units in Sweden between December, 2002 and December, 2006. All patients were started on methotrexate. After 3-4 months, those who failed treatment were randomly assigned (1:1) to group A (conventional treatment; additional sulfasalazine and hydroxychloroquine) or group B (biological treatment; additional infliximab). Randomisation was done with a computer-generated sequence. We analysed clinical outcomes at months 18 and 24 by the response criteria of the American College of Rheumatology and the European League Against Rheumatism, and radiographs of patients' hands and feet at months 12 and 24 using the Van der Heijde modification of the Sharp score. Analysis was by intention to treat. This trial is registered with www.ClinicalTrials.gov, number NCT00764725. Of 493 screened individuals, we enrolled 487, of whom 258 were randomly allocated to treatment. The proportion of patients in group B who received a EULAR-defined good response was non-significantly greater than it was in group A at 18 months (49 of 128 [38%] vs 38 of 130 [29%]) and at 24 months (49 of 128 [38%] vs 40 of 130 [31%]; p=0·204). After 24 months, radiological disease progression was greater in patients in group A than it was in those in group B (mean 7·23 [SD 12·72] vs 4·00 [10·0]; p=0·009). We recorded three serious adverse events: an extended generalised illness in group A, an extended febrile episode in group B, and a generalised illness in group B. Additional biological treatment is a valid option for patients who fail initial methotrexate treatment. However, improved clinical outcomes after 12 months and better radiographical results after 24 months should be weighed against the absence of a convincing clinical difference at 24 months and substantially higher costs. Therefore, for many patients who fail initial methotrexate treatment, add-on treatment with disease-modifying antirheumatic drugs is an appropriate treatment option. Swedish Rheumatism Association, Stockholm County, and Schering-Plough/Merck Sharp and Dohme.
    No preview · Article · Mar 2012 · The Lancet
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    ABSTRACT: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. 1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively. Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.
    No preview · Article · Mar 2012 · Annals of the rheumatic diseases
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    Katerina Chatzidionysiou · Jonas Eriksson · Johan Askling · Ronald F. van Vollenhoven
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    ABSTRACT: Background/purpose The purpose of this study was to determine whether patients who failed one anti-TNF benefit from switching to another anti-TNF and whether the specific order of agents and reason for switch is significant. Methods Data from the ARTIS registry were used. Patients with RA, who received an anti-TNF (etanercept (ETA), adalimumab (ADA) or infliximab (INF)) as first biologic and subsequently switched to an alternative anti-TNF, were included in the analysis. Treatment segments were analysed according to DAS28 and HAQ reduction and EULAR response at 6 months after baseline. Treatment results were analysed for each biologic, by type of previous anti-TNF and reason for discontinuation (primary and secondary inefficacy or intolerance). Multiple treatment segments with the same anti-TNF were disregarded for this analysis. Results A total of 1080 patients were included. Of these, 520 switched to ETA, 466 to ADA, and 94 to INF. Complete data were available for appr. 50% of patients and were evenly distributed between groups. At baseline (BL=start of 2nd anti-TNF) no differences in age, sex, disease duration, RF, HAQ and concomitant NSAIDs were observed between groups. BL DAS28 (mean±SD) was significantly lower for ADA (4.79±1.32) than ETA (5.15±1.32, p<0.0001) and INF (5.13±1.22, p=0.04). INF was more often combined with DMARDs (81.9%) than ETA (69.3%, p=0.007) and ADA (65.7%, p=0.001), but less often with glucocorticoids (39.4%) than ETA (51.2%, p=0.02) and ADA (50.6%, p=0.03). Significant clinical improvements were observed for the whole cohort of patients. DAS28 improvement at 6 months was 1.59±1.47 for ETA, 1.17±1.35 for INF and 1.00±1.32 for ADA (p=0.002 ETA vs ADA, p=0.29 ETA vs INF; p values adjusted for age, sex, BL DAS28, conc DMARDs and glucocorticoids). HAQ improvement at 6 months =0.26±0.52 for ETA, 0.14±0.50 for INF and 0.14±0.43 for ADA (adjusted p=0.42 ETA vs INF, p=0.23 ETA vs ADA). The percentages of EULAR Good/Moderate/Non-responders were 28/43/29% for ETA, 21/46/33% for INF and 17/45/38% for ADA (p=0.02 between groups). In table 1 the effectiveness of each anti-TNF by type and reason for discontinuation of the previous anti-TNF is summarised. Conclusions In this large observational cohort, patients who failed anti-TNF therapy do benefit from switching to other TNF inhibitors. ETA as 2nd anti-TNF yielded significantly greater DAS28 reductions than INF and ADA, but due to the relatively large number of incomplete data this finding must be interpreted with caution. For patients who discontinued anti-TNF because of secondary inefficacy, switching to ETA appeared more effective than switching to ADA.
    Preview · Article · Feb 2012 · Annals of the Rheumatic Diseases
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    K Chatzidionysiou · R F van Vollenhoven
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    ABSTRACT: Chatzidionysiou K, van Vollenhoven RF (Karolinska Institutet, Stockholm, Sweden). When to initiate and discontinue biologic treatments for rheumatoid arthritis (Review). J Intern Med 2011; 269: 614–625. The introduction of biologic therapies heralded a new era in the treatment for chronic inflammatory autoimmune diseases of which rheumatoid arthritis is one of the most prevalent. From a scientific point of view, these therapies demonstrated that the targeting of individual cytokines or cell-surface markers is a very effective approach. For the physician, the appropriate selection of patients in whom these therapies should be initiated is critical, as is the even more contentious issue of whether these therapies can or should be discontinued in selected patients with excellent clinical responses. Whereas the former issue has been addressed in a large number of clinical trials and observational studies, the latter remains poorly investigated and is currently the subject of further study.
    Preview · Article · Jun 2011 · Journal of Internal Medicine