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10. Perspective of Dutch Patients with Gout on Continuation or Discontinuation of Urate‐Lowering Therapy During Remission: A Mixed‐Methods Study.

Author

Peeters, Iris Rose, Veenstra, Frouwke, Wanten, Sophie A. C., Vriezekolk, Johanna E., van den Ende, Cornelia H., den Broeder, Alfons A., van Herwaarden, Noortje, Verhoef, Lise M., and Flendrie, Marcel

Subjects
SEMI-structured interviews, GOUT, THEMATIC analysis, PATIENTS' attitudes, SYMPTOMS
Abstract

Objective: Long‐term gout management is based on reducing serum urate by using urate‐lowering therapy (ULT). A lifelong treat‐to‐target approach is advocated, although a ULT (taper to) stop attempt can be considered (treat‐to‐avoid symptoms approach) during remission. Exploring the beliefs of patients with gout on long‐term ULT strategies during remission is important for optimizing gout management. We aimed to identify factors that influence the decision for continuation or discontinuation of ULT and to determine their relative importance according to patients with gout in remission. Methods: A mixed‐methods design was used. First, semistructured interviews (substudy 1) were conducted to identify barriers and facilitators for the (dis)continuation of ULT using inductive thematic analysis. Afterwards, these barriers/facilitators were summarized into neutrally phrased items and used in a maximum difference scaling study (substudy 2) to determine their relative importance using the rescaled probability score. Results: Substudies 1 and 2 included 18 and 156 patients, respectively. Substudy 1 yielded 22 items within 10 overarching themes. Substudy 2 revealed that the perceived risk of joint damage and gout flares and that ULT use gives some assurance were the most important items. The costs, ease of receiving ULT, and its practical use were the least important items. Conclusion: These results can aid shared decision‐making and provide input for what is important to discuss with patients with gout in remission when they consider ULT discontinuation. The emphasis should be on the risk of having gout flares and joint damage, not so much on facilitating how easily medication is received. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Long-term clinical and radiological effectiveness and safety of ultralow doses of rituximab in rheumatoid arthritis: observational extension of the REDO trial

Author

den Broeder, Nathan, primary, Verhoef, Lise, additional, de Man, Yaël A, additional, Kok, Marc R, additional, Thurlings, Rogier, additional, van der Weele, Wilfred, additional, van den Bemt, Bart JF, additional, van den Hoogen, Frank HJ, additional, van der Maas, Aatke, additional, and den Broeder, Alfons A, additional

Published
2024
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16. Effectiveness of longstanding exercise therapy compared with usual care for people with rheumatoid arthritis and severe functional limitations: a randomised controlled trial

Author

Teuwen, Max M H, primary, van Weely, Salima F E, additional, Vliet Vlieland, Thea P M, additional, van Wissen, Maria A T, additional, Peter, Wilfred F, additional, den Broeder, Alfons A, additional, van Schaardenburg, Dirkjan, additional, van den Hout, Wilbert B, additional, Van den Ende, Cornelia H M, additional, and Gademan, Maaike G J, additional

Published
2024
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17. Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial

Author

Wientjes, Maike H. M., Atiqi, Sadaf, Wolbink, Gerrit Jan, Nurmohamed, Michael T., Boers, Maarten, Rispens, Theo, de Vries, Annick, van Vollenhoven, Ronald F., van den Bemt, Bart J. F., and den Broeder, Alfons A.

Published
2021
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20. Functional limitations of people with rheumatoid arthritis or axial spondyloarthritis and severe functional disability: a cross-sectional descriptive study

Author

Teuwen, Max M. H., primary, van Weely, Salima F. E., additional, Vliet Vlieland, Thea P. M., additional, Douw, Thom, additional, van Schaardenburg, Dirkjan, additional, den Broeder, Alfons A., additional, van Tubergen, Astrid M., additional, van Wissen, Maria A. T., additional, van den Ende, Cornelia H. M., additional, and Gademan, Maaike G. J., additional

Published
2023
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24. NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium

Author

Manuel Sánchez-Maldonado, Jose, Martínez-Bueno, Manuel, Canhão, Helena, ter Horst, Rob, Muñoz-Peña, Sonia, Moñiz-Díez, Ana, Rodríguez-Ramos, Ana, Escudero, Alejandro, Sorensen, Signe B., Hetland, Merete L., Ferrer, Miguel A., Glintborg, Bente, Filipescu, Ileana, Pérez-Pampin, Eva, Conesa-Zamora, Pablo, García, Antonio, den Broeder, Alfons, De Vita, Salvatore, Hove Jacobsen, Svend Erik, Collantes, Eduardo, Quartuccio, Luca, Netea, Mihai G., Li, Yang, Fonseca, João E., Jurado, Manuel, López-Nevot, Miguel Ángel, Coenen, Marieke J. H., Andersen, Vibeke, Cáliz, Rafael, and Sainz, Juan

Published
2020
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28. Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study

Author

van der Togt, Céleste J T, primary, Van den Bemt, Bart, additional, Aletaha, Daniel, additional, Alten, Rieke, additional, Chatzidionysiou, Katerina, additional, Galloway, James, additional, Isaac, John, additional, Mulleman, Denis, additional, Verschueren, P, additional, Vulto, Arnold G, additional, Welsing, Paco M J, additional, Verhoef, Lise, additional, and den Broeder, Alfons A, additional

Published
2023
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29. Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases:results from an umbrella review and international Delphi study

Author

Van Der Togt, Céleste J.T., Van Den Bemt, Bart, Aletaha, Daniel, Alten, Rieke, Chatzidionysiou, Katerina, Galloway, James, Isaac, John, Mulleman, Denis, Verschueren, P., Vulto, Arnold G., Welsing, Paco M.J., Verhoef, Lise, Den Broeder, Alfons A., Van Der Togt, Céleste J.T., Van Den Bemt, Bart, Aletaha, Daniel, Alten, Rieke, Chatzidionysiou, Katerina, Galloway, James, Isaac, John, Mulleman, Denis, Verschueren, P., Vulto, Arnold G., Welsing, Paco M.J., Verhoef, Lise, and Den Broeder, Alfons A.

Abstract

Objectives To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the treatment of inflammatory rheumatic diseases, specifically rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. Methods Following EULAR procedures, an international task force was formed, consisting of 13 experts in rheumatology, epidemiology and pharmacology from seven European countries. Twelve strategies for cost-effective use of b/tsDMARDs were identified through individual and group discussion. For each strategy, PubMed and Embase were systematically searched for relevant English-language systematic reviews and, for six strategies, additionally for randomised controlled trials (RCTs). Thirty systematic reviews and 21 RCTs were included. Based on the evidence, a set of overarching principles and points to consider was formulated by the task force using a Delphi procedure. Level of evidence (1a-5) and grade (A-D) were determined for each point to consider. Individual voting on the level of agreement (LoA; between 0 (completely disagree) and 10 (completely agree)) was performed anonymously. Results The task force agreed on five overarching principles. For 10 of 12 strategies, the evidence was sufficient to formulate one or more points to consider, leading to 20 in total, regarding response prediction, drug formulary use, biosimilars, loading doses, low-dose initial therapy, concomitant conventional synthetic DMARD use, route of administration, medication adherence, disease activity-guided dose optimisation and non-medical drug switching. Ten points to consider (50%) were supported by level 1 or 2 evidence. The mean LoA (SD) varied between 7.9 (1.2) and 9.8 (0.4). Conclusion These points to consider can be used in rheumatology practices and complement inflammatory rheumatic disease treatment guidelines to incorporate cost-effectiveness in b/tsDMARD treatment.

Published
2023

30. Genome-wide Association Study of Methotrexate-Induced Liver Injury in Rheumatoid Arthritis Patients

Author

Eektimmerman, Frank, Swen, Jesse J., den Broeder, Alfons A., Hazes, Johanna M.W., Kurreeman, Fina S., Verstappen, Suzanne M.M., Nair, Nisha, Pawlik, Andrzej, Nurmohamed, Mike T., Dolžan, Vita, Böhringer, Stefan, Allaart, Cornelia F., Guchelaar, Henk Jan, Eektimmerman, Frank, Swen, Jesse J., den Broeder, Alfons A., Hazes, Johanna M.W., Kurreeman, Fina S., Verstappen, Suzanne M.M., Nair, Nisha, Pawlik, Andrzej, Nurmohamed, Mike T., Dolžan, Vita, Böhringer, Stefan, Allaart, Cornelia F., and Guchelaar, Henk Jan

Abstract

Hepatotoxicity is a serious adverse drug reaction related to methotrexate (MTX). However, the cause of drug-induced liver injury (DILI) is still unclear and unpredictable. Genetic risk factors may predispose for MTX-DILI. Therefore, we conducted a nested case-control genome-wide association study to explore genetic risk factors associated with MTX-DILI. Seven international groups contributed blood samples and data of patients with rheumatoid arthritis who used MTX. MTX-DILI was defined as an alanine aminotransferase (ALT) level of at least three times the upper limit of normal (ULN), to increase contrast controls ALT levels did not raise above two times the ULN. Per study site, control subjects and patients with MTX-DILI (ratio 3:1) were matched for age, gender, and duration of MTX use. Patients were genotyped using Illumina GSA MD-24v1-0 and data were imputed using the 1000 Genomes reference panel. Single-nucleotide polymorphisms (SNPs) were analyzed using an additive genetic model, corrected for sex, country, and age. A P-value of ≤ 5 × 10−8 was considered significant, whereas a P-value of ≤ 5 × 10−6 was considered suggestive. A total of 108 MTX-DILI cases and 311 controls were included for association analysis. None of the SNPs were significantly associated with MTX-DILI. However, we found seven suggestive genetic variants associated with MTX-DILI (P-values 7.43 × 10−8 to 4.86 × 10−6). Of those, five SNPs were in the intronic protein-coding regions of FTCDNL1, BCOR, FGF14, RBMS3, and PFDN4/DOK5. Investigation of candidates SPATA9 (rs72783407), PLCG2 (rs60427389), RAVER2 (rs72675408), JAK1 (rs72675451), PTPN2 (rs2476601), MTHFR C677T (rs1801133), and into the HLA region did not show significant findings. No genetic variants associated with MTX-DILI were found, whereas suggestive SNPs need further investigation.

Published
2023

31. Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis

Author

van der Togt, Celeste J. T., Ten Cate, David F., van den Bemt, Bart J. F., Rahamat-Langendoen, Janette, den Broeder, Nathan, den Broeder, Alfons A., van der Togt, Celeste J. T., Ten Cate, David F., van den Bemt, Bart J. F., Rahamat-Langendoen, Janette, den Broeder, Nathan, and den Broeder, Alfons A.

Abstract

OBJECTIVES: In patients with RA treated with (ultra-)low-dose rituximab (RTX), we investigated the association of dosing and timing of RTX on seroconversion after a third coronavirus disease 2019 (COVID-19) vaccination and the persistence of humoral response after a two-dose vaccination. MATERIAL AND METHODS: In this monocentre observational study, patients from the COVAC cohort were included in the third vaccine analysis if humoral response was obtained 2-6 weeks after a third vaccination in previous non-responders and in the persistence analysis if a follow-up humoral response was obtained before a third vaccination in previous responders. Dichotomization between positive and negative response was based on the assay cut-off. The association between the latest RTX dose before first vaccination, timing between the latest RTX dose and vaccination and response was analysed with univariable logistic regression. RESULTS: Of the 196 patients in the cohort, 98 were included in the third vaccine analysis and 23 in the persistence analysis. Third vaccination response was 19/98 (19%) and was higher for 200 mg RTX users [5/13 (38%)] than for 500 and 1000 mg users [7/37 (19%) and 7/48 (15%), respectively]. Non-significant trends were seen for higher response with lower dosing [200 vs 1000 mg: odds ratio (OR) 3.66 (95% CI 0.93, 14.0)] and later timing [per month since infusion: OR 1.16 (95% CI 0.97, 1.35)]. Humoral response persisted in 96% (22/23) and 89% (8/9) of patients who received RTX between the two measurements. CONCLUSIONS: Repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy. A once positive humoral response after COVID-19 vaccination persists irrespective of intercurrent RTX infusion. Study registration. Netherlands Trial Registry (https://www.trialregister.nl/), NL9342.

Published
2023

32. What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis

Author

Research UMC Utrecht, Onderzoek Reumatologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Messelink, Marianne A., Den Broeder, Alfons A., Marinelli, Florine E., Michgels, Edwin, Verschueren, P., Aletaha, Daniel, Tekstra, Janneke, Welsing, Paco M.J., Research UMC Utrecht, Onderzoek Reumatologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Messelink, Marianne A., Den Broeder, Alfons A., Marinelli, Florine E., Michgels, Edwin, Verschueren, P., Aletaha, Daniel, Tekstra, Janneke, and Welsing, Paco M.J.

Published
2023

33. Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study

Author

UMC Utrecht Academie, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Van Der Togt, Céleste J.T., Van Den Bemt, Bart, Aletaha, Daniel, Alten, Rieke, Chatzidionysiou, Katerina, Galloway, James, Isaac, John, Mulleman, Denis, Verschueren, P., Vulto, Arnold G., Welsing, Paco M.J., Verhoef, Lise, Den Broeder, Alfons A., UMC Utrecht Academie, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Van Der Togt, Céleste J.T., Van Den Bemt, Bart, Aletaha, Daniel, Alten, Rieke, Chatzidionysiou, Katerina, Galloway, James, Isaac, John, Mulleman, Denis, Verschueren, P., Vulto, Arnold G., Welsing, Paco M.J., Verhoef, Lise, and Den Broeder, Alfons A.

Published
2023

34. Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium

Author

Sánchez-Maldonado, Jose M., Cáliz, Rafael, Canet, Luz, Horst, Rob ter, Bakker, Olivier, den Broeder, Alfons A., Martínez-Bueno, Manuel, Canhão, Helena, Rodríguez-Ramos, Ana, Lupiañez, Carmen B., Soto-Pino, María José, García, Antonio, Pérez-Pampin, Eva, González-Utrilla, Alfonso, Escudero, Alejandro, Segura-Catena, Juana, Netea-Maier, Romana T., Ferrer, Miguel Ángel, Collantes-Estevez, Eduardo, López Nevot, Miguel Ángel, Li, Yang, Jurado, Manuel, Fonseca, João E., Netea, Mihai G., Coenen, Marieke J. H., and Sainz, Juan

Published
2019
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35. Non‐Medical Switching from Tocilizumab to Sarilumab in Rheumatoid Arthritis Patients with Low Disease Activity, an Observational Study.

Author

den Broeder, Nathan, den Broeder, Alfons A., Verhoef, Lise M., van den Hoogen, Frank H. J., van der Maas, Aatke, and van den Bemt, Bart J. F.

Subjects
RHEUMATOID arthritis, TOCILIZUMAB, SCIENTIFIC observation, JUDGMENT (Psychology), PATIENT safety
Abstract

Tocilizumab and sarilumab are IL‐6‐receptor antagonists registered for rheumatoid arthritis (RA), with equal effectiveness and safety. Switching from tocilizumab to sarilumab could be a strategy to reduce injection burden, in case of drug shortages, and to reduce costs. This study therefore aims to investigate the effectiveness and safety of switching patients with RA with well‐controlled disease under tocilizumab treatment to sarilumab. Patients with RA with low Disease Activity Score 28 (DAS28;‐CRP < 2.9 or < 3.5 with clinical judgment), on stable dose tocilizumab (> 6 months) were offered to switch to sarilumab. Patients who switched and consented were followed for 6 months. Sarilumab was started at 200 mg and double the last tocilizumab interval. Co‐primary outcomes at 6 months were (i) the 90% confidence interval (CI) of DAS28‐CRP change from baseline compared with the non‐inferiority margin of 0.6 and (ii) the 90% CI of the proportion of patients persisting with sarilumab, compared with a prespecified minimum of 70%. Of 50 invited patients, 25 agreed to switch to sarilumab, and 23 patients switched and were included. One patient was lost to follow‐up immediately after inclusion, therefore 22 patients are included in the analyses. At 6 months, mean change in DAS28‐CRP was 0.48 (90% CI: 0.11–0.87), compared with the non‐inferiority margin of 0.6. Sarilumab persistence was 68% (90% CI: 51–82%, 15 out of 22 patients), compared with the prespecified minimum of 70%. Non‐medical switching from tocilizumab to sarilumab in patients doing well on tocilizumab failed to show non‐inferiority regarding disease activity and drug persistence. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Genome‐wide association study of methotrexate‐induced liver injury in rheumatoid arthritis patients

Author

Eektimmerman, Frank, primary, Swen, Jesse J., additional, den Broeder, Alfons A., additional, Hazes, Johanna M.W., additional, Kurreeman, Fina S., additional, Verstappen, Suzanne M.M., additional, Nair, Nisha, additional, Pawlik, Andrzej, additional, Nurmohamed, Mike T., additional, Dolžan, Vita, additional, Böhringer, Stefan, additional, Allaart, Cornelia F., additional, and Guchelaar, Henk‐Jan, additional

Published
2023
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38. The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study

Author

Wientjes, Maike H M, primary, Ulijn, Evy, additional, Kievit, Wietske, additional, Landewé, Robert B M, additional, Meek, Inger, additional, den Broeder, Nathan, additional, van Herwaarden, Noortje, additional, van den Bemt, Bart J F, additional, Verhoef, Lise M, additional, and den Broeder, Alfons A, additional

Published
2022
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40. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

Author

Smolen, Josef S., Landewé, Robert B. M., Bergstra, Sytske Anne, Kerschbaumer, Andreas, Sepriano, Alexandre, Aletaha, Daniel, Caporali, Roberto, Edwards, Christopher John, Hyrich, Kimme L., Pope, Janet E., de Souza, Savia, Stamm, Tanja A., Takeuchi, Tsutomu, Verschueren, Patrick, Winthrop, Kevin L., Balsa, Alejandro, Bathon, Joan M., Buch, Maya H., Burmester, Gerd R., Buttgereit, Frank, Cardiel, Mario Humberto, Chatzidionysiou, Katerina, Codreanu, Catalin, Cutolo, Maurizio, den Broeder, Alfons A., el Aoufy, Khadija, Finckh, Axel, Fonseca, João Eurico, Gottenberg, Jacques-Eric, Haavardsholm, Espen A., Iagnocco, Annamaria, Lauper, Kim, Li, Zhanguo, McInnes, Iain B., Mysler, Eduardo F., Nash, Peter, Poor, Gyula, Ristic, Gorica G., Rivellese, Felice, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Stoilov, Nikolay, Strangfeld, Anja, van der Helm-van Mil, Annette, van Duuren, Elsa, Vliet Vlieland, Theodora P. M., Westhovens, René, van der Heijde, D. sirée, Clinical Immunology and Rheumatology, and AII - Inflammatory diseases

Subjects
Arthritis, Rheumatoid, Biological Therapy, All institutes and research themes of the Radboud University Medical Center, Rheumatology, Arthritis, Rheumatoid, Antirheumatic Agents, Immunology, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract

ObjectivesTo provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

Published
2023

43. Correction: Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients

Author

Canet, Luz M., Sánchez-Maldonado, Jose M., Cáliz, Rafael, Rodríguez-Ramos, Ana, Lupiañez, Carmen B., Canhão, Helena, Martínez-Bueno, Manuel, Escudero, Alejandro, Segura-Catena, Juana, Sorensen, Signe B., Hetland, Merete L., Soto-Pino, María José, Ferrer, Miguel A., García, Antonio, Glintborg, Bente, Filipescu, Ileana, Pérez-Pampin, Eva, González-Utrilla, Alfonso, Nevot, Miguel Ángel López, Conesa-Zamora, Pablo, den Broeder, Alfons, De Vita, Salvatore, Jacobsen, Sven Erik Hobe, Collantes-Estevez, Eduardo, Quartuccio, Luca, Canzian, Federico, Fonseca, João E., Coenen, Marieke J. H., Andersen, Vibeke, and Sainz, Juan

Published
2019
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44. 2022 update

Author

Smolen, Josef S., Landewé, Robert B.M., Bergstra, Sytske Anne, Kerschbaumer, Andreas, Sepriano, Alexandre, Aletaha, Daniel, Caporali, Roberto, Edwards, Christopher John, Hyrich, Kimme L., Pope, Janet E., De Souza, Savia, Stamm, Tanja A., Takeuchi, Tsutomu, Verschueren, Patrick, Winthrop, Kevin L., Balsa, Alejandro, Bathon, Joan M., Buch, Maya H., Burmester, Gerd R., Buttgereit, Frank, Cardiel, Mario Humberto, Chatzidionysiou, Katerina, Codreanu, Catalin, Cutolo, Maurizio, Den Broeder, Alfons A., El Aoufy, Khadija, Finckh, Axel, Fonseca, João Eurico, Gottenberg, Jacques Eric, Haavardsholm, Espen A., Iagnocco, Annamaria, Lauper, Kim, Li, Zhanguo, McInnes, Iain B., Mysler, Eduardo F., Nash, Peter, Poor, Gyula, Ristic, Gorica G., Rivellese, Felice, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Stoilov, Nikolay, Strangfeld, Anja, Van Der Helm-Van Mil, Annette, Van Duuren, Elsa, Vliet Vlieland, Theodora P.M., Westhovens, René, Van Der Heijde, Désirée, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Comprehensive Health Research Centre (CHRC) - pólo NMS

Subjects
Arthritis, Rheumatoid, Biological Therapy, Rheumatology, Biochemistry, Genetics and Molecular Biology(all), Antirheumatic Agents, Immunology, Immunology and Allergy
Abstract

Funding Information: This study was funded by European League Against Rheumatism. Publisher Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. Methods: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. Results: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. Conclusions: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost. publishersversion published

Published
2022

47. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

Author

Smolen, Josef S, primary, Landewé, Robert B M, additional, Bergstra, Sytske Anne, additional, Kerschbaumer, Andreas, additional, Sepriano, Alexandre, additional, Aletaha, Daniel, additional, Caporali, Roberto, additional, Edwards, Christopher John, additional, Hyrich, Kimme L, additional, Pope, Janet E, additional, de Souza, Savia, additional, Stamm, Tanja A, additional, Takeuchi, Tsutomu, additional, Verschueren, Patrick, additional, Winthrop, Kevin L, additional, Balsa, Alejandro, additional, Bathon, Joan M, additional, Buch, Maya H, additional, Burmester, Gerd R, additional, Buttgereit, Frank, additional, Cardiel, Mario Humberto, additional, Chatzidionysiou, Katerina, additional, Codreanu, Catalin, additional, Cutolo, Maurizio, additional, den Broeder, Alfons A, additional, El Aoufy, Khadija, additional, Finckh, Axel, additional, Fonseca, João Eurico, additional, Gottenberg, Jacques-Eric, additional, Haavardsholm, Espen A, additional, Iagnocco, Annamaria, additional, Lauper, Kim, additional, Li, Zhanguo, additional, McInnes, Iain B, additional, Mysler, Eduardo F, additional, Nash, Peter, additional, Poor, Gyula, additional, Ristic, Gorica G, additional, Rivellese, Felice, additional, Rubbert-Roth, Andrea, additional, Schulze-Koops, Hendrik, additional, Stoilov, Nikolay, additional, Strangfeld, Anja, additional, van der Helm-van Mil, Annette, additional, van Duuren, Elsa, additional, Vliet Vlieland, Theodora P M, additional, Westhovens, René, additional, and van der Heijde, Désirée, additional

Published
2022
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