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Rheumatoid Arthritis: HELP
Articles by Maarten Boers
Based on 114 articles published since 2008
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Between 2008 and 2019, M. Boers wrote the following 114 articles about Arthritis, Rheumatoid.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. 2014

Smolen, Josef S / Landewé, Robert / Breedveld, Ferdinand C / Buch, Maya / Burmester, Gerd / Dougados, Maxime / Emery, Paul / Gaujoux-Viala, Cécile / Gossec, Laure / Nam, Jackie / Ramiro, Sofia / Winthrop, Kevin / de Wit, Maarten / Aletaha, Daniel / Betteridge, Neil / Bijlsma, Johannes W J / Boers, Maarten / Buttgereit, Frank / Combe, Bernard / Cutolo, Maurizio / Damjanov, Nemanja / Hazes, Johanna M W / Kouloumas, Marios / Kvien, Tore K / Mariette, Xavier / Pavelka, Karel / van Riel, Piet L C M / Rubbert-Roth, Andrea / Scholte-Voshaar, Marieke / Scott, David L / Sokka-Isler, Tuulikki / Wong, John B / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, , Vienna, Austria. ·Ann Rheum Dis · Pubmed #24161836.

ABSTRACT: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.

2 Guideline Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. 2008

Aletaha, D / Landewe, R / Karonitsch, T / Bathon, J / Boers, M / Bombardier, C / Bombardieri, S / Choi, H / Combe, B / Dougados, M / Emery, P / Gomez-Reino, J / Keystone, E / Koch, G / Kvien, T K / Martin-Mola, E / Matucci-Cerinic, M / Michaud, K / O'Dell, J / Paulus, H / Pincus, T / Richards, P / Simon, L / Siegel, J / Smolen, J S / Sokka, T / Strand, V / Tugwell, P / van der Heijde, D / van Riel, P / Vlad, S / van Vollenhoven, R / Ward, M / Weinblatt, M / Wells, G / White, B / Wolfe, F / Zhang, B / Zink, A / Felson, D / Anonymous4270609 / Anonymous4280609. ·Medical University of Vienna, Vienna, Austria. daniel.aletaha@meduniwien.ac.at ·Arthritis Rheum · Pubmed #18821648.

ABSTRACT: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

3 Editorial Patient-reported remission in rheumatoid arthritis. 2013

van Tuyl, Lilian H D / Boers, Maarten. · ·J Rheumatol · Pubmed #23547253.

ABSTRACT: -- No abstract --

4 Editorial Patient's global assessment of disease activity: what are we measuring? 2012

van Tuyl, Lilian H D / Boers, Maarten. · ·Arthritis Rheum · Pubmed #22614670.

ABSTRACT: -- No abstract --

5 Editorial RAID: a valid tool to quantify the impact of rheumatoid arthritis. But what impact will it have on the core set for trials? 2011

Boers, Maarten. · ·Ann Rheum Dis · Pubmed #21470971.

ABSTRACT: -- No abstract --

6 Editorial Syk kinase inhibitors for rheumatoid arthritis: trials and tribulations. 2011

Boers, Maarten. · ·Arthritis Rheum · Pubmed #21279987.

ABSTRACT: -- No abstract --

7 Editorial Updating the 2003 European regulatory requirements for registering disease-modifying drugs to be used in the treatment of rheumatoid arthritis. 2011

Smolen, Josef S / Boers, Maarten / Abadie, Eric C / Breedveld, Ferdinand C / Emery, Paul / Bardin, Thomas / Goel, Niti / Ethgen, Dominique J / Avouac, Bernard P / Durez, Patrick / Flamion, Bruno / Laslop, Andrea / Miossec, Pierre / Reiter, Susanne / Reginster, Jean-Yves / Anonymous890684. · ·Rheumatology (Oxford) · Pubmed #21242246.

ABSTRACT: -- No abstract --

8 Editorial Cost-effectiveness of biologics as first-line treatment of rheumatoid arthritis: case closed? 2009

Boers, Maarten. · ·Ann Intern Med · Pubmed #19884628.

ABSTRACT: -- No abstract --

9 Editorial Just released from the ASAS factory! First steps towards a disease activity score for ankylosing spondylitis. 2009

Boers, Maarten. · ·Ann Rheum Dis · Pubmed #19088258.

ABSTRACT: -- No abstract --

10 Editorial Pathophysiology of rheumatoid arthritis: split or lump? 2008

Boers, Maarten. · ·Arthritis Rheum · Pubmed #18821696.

ABSTRACT: -- No abstract --

11 Editorial A call for pragmatic treatment trials in rheumatoid arthritis. 2008

Boers, Maarten. ·Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. keb.info@vumc.nl ·Nat Clin Pract Rheumatol · Pubmed #18446137.

ABSTRACT: -- No abstract --

12 Review EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. 2017

Smolen, Josef S / Landewé, Robert / Bijlsma, Johannes / Burmester, Gerd / Chatzidionysiou, Katerina / Dougados, Maxime / Nam, Jackie / Ramiro, Sofia / Voshaar, Marieke / van Vollenhoven, Ronald / Aletaha, Daniel / Aringer, Martin / Boers, Maarten / Buckley, Chris D / Buttgereit, Frank / Bykerk, Vivian / Cardiel, Mario / Combe, Bernard / Cutolo, Maurizio / van Eijk-Hustings, Yvonne / Emery, Paul / Finckh, Axel / Gabay, Cem / Gomez-Reino, Juan / Gossec, Laure / Gottenberg, Jacques-Eric / Hazes, Johanna M W / Huizinga, Tom / Jani, Meghna / Karateev, Dmitry / Kouloumas, Marios / Kvien, Tore / Li, Zhanguo / Mariette, Xavier / McInnes, Iain / Mysler, Eduardo / Nash, Peter / Pavelka, Karel / Poór, Gyula / Richez, Christophe / van Riel, Piet / Rubbert-Roth, Andrea / Saag, Kenneth / da Silva, Jose / Stamm, Tanja / Takeuchi, Tsutomu / Westhovens, René / de Wit, Maarten / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands. · Zuyderland Medical Center, Heerlen, The Netherlands. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany. · Rheumatology Department, Karolinska Institute, Stockholm, Sweden. · Rhumatologie B, Hopital Cochin, Paris, France. · NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands. · Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK. · Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA. · Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. · Centro de Investigación Clínica de Morelia SC, Michoacán, México. · Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France. · Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy. · Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands. · Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland. · Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain. · Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France. · Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France. · Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK. · V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. · European League Against Rheumatism, Zurich, Switzerland. · Cyprus League against Rheumatism, Nicosia, Cyprus. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Rheumatology and Immunology, Beijing University People's Hospital, Beijing, China. · Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France. · Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Organización Médica de Investigación, Buenos Aires, Argentina. · Department of Medicine, University of Queensland, Queensland, Australia. · Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic. · National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest, Hungary. · Rheumatology Department, FHU ACRONIM, Pellegrin Hospital and UMR CNRS 5164, Bordeaux University, Bordeaux, France. · Department of Rheumatology, Bernhoven, Uden, The Netherlands. · University of Cologne, Cologne, Germany. · Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Serviço de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal. · Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Keio University School of Medicine, Keio University Hospital, Tokyo, Japan. · Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #28264816.

ABSTRACT: Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

13 Review "Official View" on Glucocorticoids in Rheumatoid Arthritis: A Systematic Review of International Guidelines and Consensus Statements. 2017

Palmowski, Yannick / Buttgereit, Thomas / Dejaco, Christian / Bijlsma, Johannes W / Matteson, Eric L / Voshaar, Marieke / Boers, Maarten / Buttgereit, Frank. ·Charité University Medicine, Berlin, Germany. · Medical University Graz, Graz, Austria. · University Medical Centre Utrecht, Utrecht, The Netherlands. · Mayo Clinic College of Medicine, Rochester, Minnesota. · University of Twente, Enschede, The Netherlands. · VU University Medical Center, Amsterdam, The Netherlands. ·Arthritis Care Res (Hoboken) · Pubmed #28029750.

ABSTRACT: OBJECTIVE: To describe the perception of the current role of systemic glucocorticoids in the management of rheumatoid arthritis (RA) by examining their importance and the current level of evidence in recent guidelines, and to identify open questions to be addressed in future guidelines and research projects. METHODS: We conducted a systematic literature review using the databases Ovid Embase, PubMed Medline, and Cochrane Library for guidelines on the pharmacologic treatment of RA. Retrieved articles were evaluated regarding their quality using the Appraisal of Guidelines for Research and Evaluation II tool and scrutinized for all relevant information concerning the use of glucocorticoids. RESULTS: All guidelines agree that glucocorticoids, especially if given at low doses and for a short duration, are an appropriate option in the treatment of RA. However, many recommendations remain vague, as reliable and detailed evidence is scarce. Important aspects of glucocorticoid therapy are partially or completely neglected, and the existing nomenclature is not used uniformly. Quality evaluation revealed flaws in many articles, concerning not only glucocorticoid-specific recommendations but also guideline quality in general. CONCLUSION: Current recommendations for use of glucocorticoids in the management of RA are suboptimal. More rigorous evaluation of doses, timing, and duration of their use is needed. Existing nomenclature on glucocorticoid therapy should be used uniformly.

14 Review Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis. 2017

Tarp, Simon / Eric Furst, Daniel / Boers, Maarten / Luta, George / Bliddal, Henning / Tarp, Ulrik / Heller Asmussen, Karsten / Brock, Birgitte / Dossing, Anna / Schjødt Jørgensen, Tanja / Thirstrup, Steffen / Christensen, Robin. ·Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark. · David Geffen School of Medicine, University of California Los Angeles, CA. · Division of Rheumatology, University of Washington, Seattle, WA, USA. · Division of Rheumatology, University of Florence, Florence, Italy. · Department of Epidemiology and Biostatistics. · Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands. · Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA. · Department of Rheumatology, Aarhus University Hospital, Aarhus N. · Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen. · Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N. · Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. ·Rheumatology (Oxford) · Pubmed #28013201.

ABSTRACT: Objectives: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA. Methods: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Results: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates. Conclusion: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. Systematic review registration number: PROSPERO CRD42014014842.

15 Review Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials. 2017

Tarp, Simon / Furst, Daniel E / Dossing, Anna / Østergaard, Mikkel / Lorenzen, Tove / Hansen, Michael S / Singh, Jasvinder A / Choy, Ernest H / Boers, Maarten / Suarez-Almazor, Maria E / Kristensen, Lars E / Bliddal, Henning / Christensen, Robin. ·Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. Electronic address: simon.tarp@regionh.dk. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA. · Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. · Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. · Department of Rheumatology, Diagnostic Centre, Silkeborg Regional Hospital, Copenhagen, Denmark. · ReumaKlinik Roskilde, Roskilde, Denmark; Gildhøj Privathospital, Brøndby, Denmark. · Medicine Service and Center for Surgical Medical Acute care Research and Transitions, VA Medical Center, Birmingham, AL; Department of Medicine at School of Medicine, Division of Epidemiology at School of Public Health, University of Alabama, Birmingham, AL; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN. · Section of Rheumatology, Arthritis Research UK and Health and Care Research Wales CREATE Centre, Cardiff University School of Medicine, Cardiff, UK. · Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands. · Section of Rheumatology and Clinical Immunology, University of Texas MD Anderson Cancer Center, Houston, TX. ·Semin Arthritis Rheum · Pubmed #27769592.

ABSTRACT: OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.

16 Review Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease. 2016

Smolen, Josef S / Collaud Basset, Sabine / Boers, Maarten / Breedveld, Ferdinand / Edwards, Christopher J / Kvien, Tore K / Miossec, Pierre / Sokka-Isler, Tuulikki / van Vollenhoven, Ronald F / Abadie, Eric C / Bruyère, Olivier / Cooper, Cyrus / Mäkinen, Heidi / Thomas, Thierry / Tugwell, Peter / Reginster, Jean-Yves / Anonymous2231055. ·Department of Internal Medicine III, Hietzing Hospital, Vienna, Austria Division of Rheumatology, Medical University Vienna, Vienna, Austria. · TRB Chemedica International SA, Geneva, Switzerland. · Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands. · Leiden University Medical Centre, Leiden, The Netherlands. · Musculoskeletal Research Unit, NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon 1, Edouard Herriot Hospital, Lyon, France. · Faculty of Health Sciences, University of Eastern Finland, Jyvaskyla Central Hospital, Jyvaskyla, Finland. · Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. · Euremed Consulting, Paris, France Universidade de Lisboa, Lisbon, Portugal. · Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium. · MRC Lifecourse Epidemiology Unit, NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK. · Rheumatology Department, Tampere University Hospital, Tampere, Finland. · Rheumatology Department, University Hospital of Saint-Etienne, Saint-Etienne, France INSERM U1059, Université de Lyon, Lyon, France. · Department of Medicine, University of Ottawa, Ottawa, Canada. ·Ann Rheum Dis · Pubmed #27037326.

ABSTRACT: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.

17 Review Remission in Rheumatoid Arthritis: Working Toward Incorporation of the Patient Perspective at OMERACT 12. 2016

van Tuyl, Lilian H / Sadlonova, Martina / Davis, Bev / Flurey, Caroline / Goel, Niti / Hewlett, Sarah E / Hill, Catherine L / Hoogland, Wijnanda / Kirwan, John R / van Schaardenburg, Dirkjan / Scholte-Voshaar, Marieke / Smolen, Josef S / Stamm, Tanja / Wells, George A / Boers, Maarten. ·From the Department of Rheumatology, and the Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria; University of Bristol, and the University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; Bristol, UK; Quintiles Inc., Morrisville; Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Queen Elizabeth Hospital Department of Rheumatology, Woodville, South Australia; University of Adelaide, The Health Observatory Woodville, South Australia, Australia; Reade/Jan van Breemen Research Institute, Amsterdam, the Netherlands; Department of Epidemiology and Community Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.L.H. van Tuyl, Postdoctoral Researcher, PhD, Department of Rheumatology, VU University Medical Center; M. Sadlonova, Occupational Therapist, MSc, Division of Rheumatology, Department of Medicine, Medical University of Vienna; B. Davis, Patient Research Partner, University of Bristol, Academic Rheumatology Unit, Bristol Royal Infirmary; C. Flurey, Research Fellow, PhD, University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; N. Goel, MD, Senior Medical Director and Adjunct Assistant Professor of Medicine, Quintiles Inc., and Division of Rheumatology, Department of Medicine, Duke University School of Medicine; S.E. Hewlett, Professor of Rheumatology Nursing, PhD, University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; Queen Elizabeth Hospital, Department of Rheumatology, Woodville; C.L. Hill, MD, Rheumatologist, Queen Elizabeth Hospital Department of Rheumatology, Woodville, University of Adelaide, Health Observatory Woodville; W. Hoogland, MD, Patient Research Partner, Department of Rheumatology, VU University Medical Center; J.R. Kirwan, Professor o ·J Rheumatol · Pubmed #25684772.

ABSTRACT: OBJECTIVE: The treatment of rheumatoid arthritis (RA) should target patient-relevant outcomes, making patient perspective on remission essential. In 2010, patients, physicians, health professionals, and researchers at the Outcome Measures in Rheumatology (OMERACT) conference developed an ambitious research agenda to study the concept of remission. Qualitative research has since helped us understand the concept of remission from the patient perspective. METHODS: During OMERACT 12, the OMERACT working group on patient perspective on remission in RA elaborated on data generated to date and discussed the methodological challenges ahead. Challenges included (1) selection of domains, (2) choice of a patient remission definition or a single domain to add to the current remission definition, and (3) the importance of pain in defining remission from a patient perspective. RESULTS: Focus in the coming years will be on increasing our understanding by identifying the most important domains from the patient perspective regarding remission and investigating how these domains can be measured. Investigation into the Rheumatoid Arthritis Impact of Disease questionnaire, disease flare, as well as the concordance of domains from our ongoing remission survey is appropriate. More data and further discussions are needed to decide on the next steps. CONCLUSION: Progress summarized over 4 years highlights the main methodological challenges discussed within the working group on patient perspective on remission in RA during OMERACT 12.

18 Review Balneotherapy (or spa therapy) for rheumatoid arthritis. An abridged version of Cochrane Systematic Review. 2015

Verhagen, A P / Bierma-Zeinstra, S M / Boers, M / Cardoso, J R / Lambeck, J / De Bie, R / De Vet, H C. ·Department of General Practice, Erasmus Medical Center, Rotterdam, The Netherlands - a.verhagen@erasmusmc.nl. ·Eur J Phys Rehabil Med · Pubmed #26158921.

ABSTRACT: BACKGROUND: Treatment options for rheumatoid arthritis (RA) include pharmacological interventions, physical therapy treatments and balneotherapy. AIM: To evaluate the benefits and harms of balneotherapy in patients with RA. DESIGN: A systematic review. POPULATION: Studies were eligible if they were randomised controlled trials consisting of participants with definitive or classical RA. METHODS: We searched various databases up to December 2014. Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures. Two review authors independently selected trials, performed data extraction and assessed risk of bias. RESULTS: This review includes nine studies involving 579 participants. Most studies showed an unclear risk of bias in most domains. We found no statistically significant differences on pain or improvement between mudpacks versus placebo (1 study; N.=45; hand RA; very low level of evidence). As for the effectiveness of additional radon in carbon dioxide baths, we found no statistically significant differences between groups for all outcomes at three-month follow-up (2 studies; N.=194; low to moderate level of evidence). We noted some benefit of additional radon at six months in pain (moderate level of evidence). One study (N.=148) compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain or in physical disability (very low level of evidence) between groups. We found no statistically significant differences in pain intensity at eight weeks, but some benefit of mineral baths in overall improvement at eight weeks compared to Cyclosporin A (1 study; N.=57; low level of evidence). CONCLUSION: Overall evidence is insufficient to show that balneotherapy is more effective than no treatment; that one type of bath is more effective than another or that one type of bath is more effective than exercise or relaxation therapy. CLINICAL REHABILITATION IMPACT: We were not able to assess any clinical relevant impact of balneotherapy over placebo, no treatment or other treatments.

19 Review Balneotherapy (or spa therapy) for rheumatoid arthritis. 2015

Verhagen, Arianne P / Bierma-Zeinstra, Sita M A / Boers, Maarten / Cardoso, Jefferson R / Lambeck, Johan / de Bie, Rob / de Vet, Henrica C W. ·Department of General Practice, Erasmus Medical Center, PO Box 2040, Rotterdam, Netherlands, 3000 CA. ·Cochrane Database Syst Rev · Pubmed #25862243.

ABSTRACT: BACKGROUND: No cure for rheumatoid arthritis (RA) is known at present, so treatment often focuses on management of symptoms such as pain, stiffness and mobility. Treatment options include pharmacological interventions, physical therapy treatments and balneotherapy. Balneotherapy is defined as bathing in natural mineral or thermal waters (e.g. mineral baths, sulphur baths, Dead Sea baths), using mudpacks or doing both. Despite its popularity, reported scientific evidence for the effectiveness or efficacy of balneotherapy is sparse. This review, which evaluates the effects of balneotherapy in patients with RA, is an update of a Cochrane review first published in 2003 and updated in 2008. OBJECTIVES: To perform a systematic review on the benefits and harms of balneotherapy in patients with RA in terms of pain, improvement, disability, tender joints, swollen joints and adverse events. SEARCH METHODS: We searched the Cochrane 'Rehabilitation and Related Therapies' Field Register (to December 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), MEDLIINE (1950 to December 2014), EMBASE (1988 to December 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to December 2014), the Allied and Complementary Medicine Database (AMED) (1985 to December 2014), PsycINFO (1806 to December 2014) and the Physiotherapy Evidence Database (PEDro). We applied no language restrictions; however, studies not reported in English, Dutch, Danish, Swedish, Norwegian, German or French are awaiting assessment. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing and recently completed trials. SELECTION CRITERIA: Studies were eligible if they were randomised controlled trials (RCTs) consisting of participants with definitive or classical RA as defined by the American Rheumatism Association (ARA) criteria of 1958, the ARA/American College of Rheumatology (ACR) criteria of 1988 or the ACR/European League Against Rheumatism (EULAR) criteria of 2010, or by studies using the criteria of Steinbrocker.Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention.The World Health Organization (WHO) and the International League Against Rheumatism (ILAR) determined in 1992 a core set of eight endpoints in clinical trials concerning patients with RA. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, performed data extraction and assessed risk of bias. We resolved disagreements by consensus and, if necessary, by third party adjudication. MAIN RESULTS: This review includes two new studies and a total of nine studies involving 579 participants. Unfortunately, most studies showed an unclear risk of bias in most domains. Four out of nine studies did not contribute to the analysis, as they presented no data.One study involving 45 participants with hand RA compared mudpacks versus placebo. We found no statistically significant differences in terms of pain on a 0 to 100-mm visual analogue scale (VAS) (mean difference (MD) 0.50, 95% confidence interval (CI) -0.84 to 1.84), improvement (risk ratio (RR) 0.96, 95% CI 0.54 to 1.70) or number of swollen joints on a scale from 0 to 28 (MD 0.60, 95% CI -0.90 to 2.10) (very low level of evidence). We found a very low level of evidence of reduction in the number of tender joints on a scale from 0 to 28 (MD -4.60, 95% CI -8.72 to -0.48; 16% absolute difference). We reported no physical disability and presented no data on withdrawals due to adverse events or on serious adverse events.Two studies involving 194 participants with RA evaluated the effectiveness of additional radon in carbon dioxide baths. We found no statistically significant differences between groups for all outcomes at three-month follow-up (low to moderate level of evidence). We noted some benefit of additional radon at six months in terms of pain frequency (RR 0.6, 95% CI 0.4 to 0.9; 31% reduction; improvement in one or more points (categories) on a 4-point scale; moderate level of evidence) and 9.6% reduction in pain intensity on a 0 to 100-mm VAS (MD 9.6 mm, 95% CI 1.6 to 17.6; moderate level of evidence). We also observed some benefit in one study including 60 participants in terms of improvement in one or more categories based on a 4-point scale (RR 2.3, 95% CI 1.1 to 4.7; 30% absolute difference; low level of evidence). Study authors did not report physical disability, tender joints, swollen joints, withdrawals due to adverse events or serious adverse events.One study involving 148 participants with RA compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain on the McGill Questionnaire or in physical disability (very low level of evidence) between balneotherapy and the other interventions. No data on improvement, tender joints, swollen joints, withdrawals due to adverse events or serious adverse events were presented.One study involving 57 participants with RA evaluated the effectiveness of mineral baths (balneotherapy) versus Cyclosporin A. We found no statistically significant differences in pain intensity on a 0 to 100-mm VAS (MD 9.64, 95% CI -1.66 to 20.94; low level of evidence) at 8 weeks (absolute difference 10%). We found some benefit of balneotherapy in overall improvement on a 5-point scale at eight weeks of 54% (RR 2.35, 95% CI 1.44 to 3.83). We found no statistically significant differences (low level of evidence) in the number of swollen joints, but some benefit of Cyclosporin A in the number of tender joints (MD 8.9, 95% CI 3.8 to 14; very low level of evidence). Physical disability, withdrawals due to adverse events and serious adverse events were not reported. AUTHORS' CONCLUSIONS: Overall evidence is insufficient to show that balneotherapy is more effective than no treatment, that one type of bath is more effective than another or that one type of bath is more effective than mudpacks, exercise or relaxation therapy.

20 Review Measurement of stiffness in patients with rheumatoid arthritis in low disease activity or remission: a systematic review. 2014

van Tuyl, Lilian H D / Lems, Willem F / Boers, Maarten. ·Department of Rheumatology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. L.vantuyl@vumc.nl. ·BMC Musculoskelet Disord · Pubmed #24476506.

ABSTRACT: BACKGROUND: Recent qualitative research has shown that stiffness is an important symptom for patients to identify remission. However, it is unclear how to measure stiffness in low disease activity. This systematic review aims to summarise the existing literature on validity of patient reported outcomes to measure stiffness in RA low disease activity states, to aid the choice for a measurement instrument. METHODS: An extensive pubmed-search was undertaken, identifying measurement instruments for patient perceived stiffness used in low disease activity. Eligible studies reported on 1) stiffness as an outcome in relation to other core set measures, 2) development of a patient reported tool to measure stiffness, or 3) comparison of two different tools to measure aspects of stiffness, all in low disease activity. RESULTS: Of 788 titles, only two studies report on validity of stiffness measures within low disease activity. Morning stiffness (MS) is reported in 44 to 80% of patients in low disease activity. A difference of 40 to 60 minutes in duration until maximum improvement is observed between active and inactive patients. Severity of MS might discriminate better between high and low disease activity compared to measurement of duration of MS. CONCLUSIONS: There is insufficient data on measurement of stiffness in the spectrum of low disease activity or remission.

21 Review Outcome measures in rheumatoid arthritis randomised trials over the last 50 years. 2013

Kirkham, Jamie J / Boers, Maarten / Tugwell, Peter / Clarke, Mike / Williamson, Paula R. ·Department of Biostatistics, University of Liverpool, L69 3GA, Liverpool, United Kingdom. prw@liv.ac.uk. ·Trials · Pubmed #24103529.

ABSTRACT: BACKGROUND: The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology. METHODS: An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study. RESULTS: Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial. CONCLUSIONS: This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities.

22 Review Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials. 2012

Tarp, Simon / Bartels, Else M / Bliddal, Henning / Furst, Daniel E / Boers, Maarten / Danneskiold-Samsøe, Bente / Rasmussen, Mette / Christensen, Robin. ·Copenhagen University Hospital, Frederiksberg, Denmark. ·Arthritis Rheum · Pubmed #22833186.

ABSTRACT: OBJECTIVE: To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs. METHODS: We performed a systematic search in Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBase via OVID, the Institute for Scientific Information Web of Science, and other sources. Eligible trials were parallel-group, randomized, placebo-controlled trials of oral NSAID therapy in RA patients for which there were extractable CRP data. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated from the differences in means of CRP levels between groups (active treatment minus placebo) divided by the pooled SDs. For the meta-analysis, a random-effects model was used to estimate the overall change in CRP level, and stratified analysis was used to examine differences among NSAIDs. RESULTS: We included 19 trials of 10 different NSAIDs. Overall, NSAIDs showed no effect on the CRP level (SMD 0.01 [95% CI -0.03, 0.06], P = 0.62). However, the prespecified stratified analysis indicated varying effects on the CRP level according to the different NSAIDs; lumiracoxib caused a statistically significant and consistent (I(2) = 0%) increase in the CRP level (SMD 0.13 [95% CI 0.01, 0.25], P = 0.037), whereas naproxen caused a statistically significant and consistent (I(2) = 0%) decrease in the CRP level (SMD -0.11 [95% CI -0.20, -0.02], P = 0.022). CONCLUSION: Overall, NSAIDs have no effect on the CRP level. However, the nonselective NSAID naproxen was associated with a significant decrease in the CRP level, whereas the cyclooxygenase 2-selective NSAID lumiracoxib was associated with a significant increase in the CRP level. This finding is interesting considering the suspected influence of NSAIDs on cardiovascular complications.

23 Review Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs. 2010

Bergman, Gert J D / Hochberg, Marc C / Boers, Maarten / Wintfeld, Neil / Kielhorn, Adrian / Jansen, Jeroen P. ·Mapi Values, Houten, The Netherlands. ·Semin Arthritis Rheum · Pubmed #20223500.

ABSTRACT: OBJECTIVES: To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS: Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI). RESULTS: Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1). CONCLUSIONS: Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.

24 Review Evidence for predictive validity of remission on long-term outcome in rheumatoid arthritis: a systematic review. 2010

van Tuyl, Lilian H D / Felson, David T / Wells, George / Smolen, Josef / Zhang, Bin / Boers, Maarten / Anonymous50652 / Anonymous60652. ·Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. L.vanTuyl@vumc.nl ·Arthritis Care Res (Hoboken) · Pubmed #20191498.

ABSTRACT: OBJECTIVE: Remission is rapidly becoming a key end point in rheumatoid arthritis (RA) clinical trials, but its definition is not satisfactory. Although it is generally believed that achieving a state of remission will lead to better structural outcome, this has not been studied systematically. As part of an undertaking to redefine remission, the current review describes the relationship between remission and long-term structural outcome. METHODS: A systematic literature search of PubMed, EMBase, and The Cochrane Library intersected 3 groups of terms: RA, remission, and long-term outcome. The search identified 1,138 records, of which 14 were relevant to the research question. RESULTS: All of the studies included in this review showed a relationship between remission and long-term structural damage or disability. Patients that achieved a state of remission, defined in various ways, showed less deterioration of function and radiographic progression compared with patients who did not reach a state of remission. CONCLUSION: Patients who achieved a state of remission were less likely to show deterioration of function and radiographic progression compared with patients who did not reach a state of remission.

25 Review Neurologic outcome of surgical and conservative treatment of rheumatoid cervical spine subluxation: a systematic review. 2009

Wolfs, Jasper F C / Kloppenburg, Margreet / Fehlings, Michael G / van Tulder, Maurits W / Boers, Maarten / Peul, Wilco C. ·Leiden University Medical Center, Leiden, The Hague, The Netherlands. jasperwolfs@hotmail.com ·Arthritis Rheum · Pubmed #19950322.

ABSTRACT: OBJECTIVE: Rheumatoid arthritis commonly involves the upper cervical spine and can cause significant neurologic morbidity and mortality. However, there is no consensus on the optimal timing for surgical intervention: whether surgery should be performed prophylactically or once neurologic deficits have become apparent. METHODS: A systematic review of the literature was performed to analyze neurologic outcome (Ranawat) and survival time (Kaplan-Meier) after surgical or conservative treatment using the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria. RESULTS: Twenty-five observational studies were selected. No randomized controlled trials (RCTs) could be found. All of the studies had a high risk of bias. Twenty-three studies reported the neurologic outcome after surgery for 752 patients. Neurologic deterioration rarely occurred in Ranawat I and II patients. Ranawat III patients did not fully recover. The 10-year survival rates were 77%, 63%, 47%, and 30% for Ranawat I, II, IIIA, and IIIB, respectively. The Ranawat IIIB patients had a significantly worse outcome. Another 185 patients treated conservatively were described in 7 studies. Neurologic deterioration rarely occurred in Ranawat I patients, but was almost inevitable in Ranawat II, IIIA, and IIIB patients. The Kaplan-Meier analysis showed a 10-year overall survival rate of 40%. CONCLUSION: There are no RCTs that compared surgery with conservative treatment. In observational studies, surgical neurologic outcomes were better than conservative treatment in all patients with cervical spine involvement, and in asymptomatic patients with no neurologic impairment (Ranawat I) the outcomes were similar; however, the evidence is weak. Survival time of surgical and conservative treatment could not be compared.

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