Publications by authors named "Suzanne M M Verstappen"

91 Publications

Changes in the illness perceptions of patients with rheumatoid arthritis over the first year of methotrexate therapy.

Authors:
James M Gwinnutt Sam Norton Kimme L Hyrich Mark Lunt Anne Barton Lis Cordingley Suzanne M M Verstappen

Rheumatology (Oxford) 2020 Nov 14. Epub 2020 Nov 14.

Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester.

Objectives: To describe the illness perceptions of patients with RA over the first year of MTX treatment, and the association between illness perceptions and outcomes.

Methods: Data came from the Rheumatoid Arthritis Medication Study (RAMS), a UK multicentre cohort study of RA patients starting MTX for the first time. Patients were assessed at baseline, and at 6 and 12 months. Patients completed the Brief Illness Perception Questionnaire (B-IPQ) at each assessment, as well as other patient-reported outcomes (PROs). The inflammation score (2-component DAS28) was calculated. Subgroups of patients with similar trajectories across the eight (B-IPQ) items were identified using a latent class growth model. Predictors of group membership were identified using multinomial logistic regression. Associations between subgroups and PROs over follow-up were assessed using linear mixed models.

Results: Three subgroups were identified in the analysis population (N = 1087): Positive illness perceptions (N = 322), Negative illness perceptions (N = 534) and Improvers (N = 231) who switched from negative to positive illness perceptions over follow-up. Baseline disability was associated with group membership [Positive vs Negative: relative risk ratio (RRR) 0.37, 95% CI: 0.25, 0.54; Improvers vs Negative: RRR 0.60, 95% CI: 0.43, 0.83], as were other PROs (pain, fatigue, anxiety, depression). The Negative group had worse disability, pain and fatigue over follow-up compared with the other groups, controlling for inflammation.

Conclusion: Negative illness perceptions are associated with poor PROs over time. The Improvers subgroup illustrated that illness perceptions can change in RA. Illness perceptions represent a potential therapeutic target that should be assessed using randomized trials.
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http://dx.doi.org/10.1093/rheumatology/keaa615DOI Listing
November 2020

Using qualitative methods for a conceptual analysis of measures of health status and presenteeism prior to a mapping study.

Authors:
Cheryl Jones Katherine Payne Suzanne M M Verstappen

Qual Life Res 2020 Nov 22;29(11):3167-3177. Epub 2020 Jul 22.

Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal & Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Objectives: The inclusion of productivity in economic evaluations is a contentious issue. Methods are currently being developed to assess how it may feasibly be included for specific interventions, such as workplace interventions (WPIs), where productivity is a key outcome. Mapping (also called cross-walking or prediction modelling) may offer a solution. Prior to producing a mapping algorithm, it is recommended that the conceptual validity between 'source' and 'target' measures be understood first. This study aimed to understand the conceptual validity of two existing measures of health status (EQ-5D; SF-6D) and presenteeism to inform the potential for a subsequent mapping algorithm.

Methods: A purposive sample of individuals who were currently working and had either rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Individuals were recruited through support groups. Semi-structured telephone interviews were conducted until data saturation (no new emerging themes) was reached. Deductive and inductive framework analysis methods were used to identify key aspects of the conditions (themes) that impact on presenteeism (working at reduced levels of health).

Results: Twenty-two (RA = 10; AS = 9; PsA = 3) employed individuals were interviewed. Deductive analysis identified evidence which confirmed the domains included in the EQ-5D and SF-6D capture those key aspects of RA, AS and PsA that increase presenteeism. Inductive analysis identified an additional theme; mental clarity, not captured by the EQ-5D or SF-6D, was also found to have a direct impact on presenteeism.

Conclusions: The results of the study indicate conceptual validity of both health status measures to predict presenteeism. The next step is to develop a mapping algorithm for presenteeism.
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http://dx.doi.org/10.1007/s11136-020-02570-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591427PMC
November 2020

Correction: Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

Authors:
Yi Pan Sam Norton James M Gwinnutt Lianne Kearsley-Fleet Deborah P M Symmons Mark Lunt Adam Young Kimme L Hyrich Suzanne M M Verstappen

PLoS One 2020;15(4):e0231481. Epub 2020 Apr 2.

[This corrects the article DOI: 10.1371/journal.pone.0215999.].
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231481PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117688PMC
April 2020

Predictors of presenteeism, absenteeism and job loss in patients commencing methotrexate or biologic therapy for rheumatoid arthritis.

Authors:
James M Gwinnutt Sarah Leggett Mark Lunt Anne Barton Kimme L Hyrich Karen Walker-Bone Suzanne M M Verstappen

Rheumatology (Oxford) 2020 10;59(10):2908-2919

Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester.

Objectives: Work is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics.

Methods: Patients aged 18-65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated.

Results: A total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts.

Conclusion: Patients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.
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http://dx.doi.org/10.1093/rheumatology/keaa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516097PMC
October 2020

Proteomic analysis to define predictors of treatment response to adalimumab or methotrexate in rheumatoid arthritis patients.

Authors:
Stephanie F Ling Nisha Nair Suzanne M M Verstappen Anne Barton Hans-Dieter Zucht Petra Budde Peter Schulz-Knappe Darren Plant

Pharmacogenomics J 2020 06 10;20(3):516-523. Epub 2019 Dec 10.

Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.

Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study.
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http://dx.doi.org/10.1038/s41397-019-0139-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253356PMC
June 2020

Long-term outcomes of patients who rate symptoms of rheumatoid arthritis as 'satisfactory'.

Authors:
James M Gwinnutt Kimme L Hyrich Mark Lunt Anne Barton Suzanne M M Verstappen

Rheumatology (Oxford) 2020 08;59(8):1853-1861

Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre.

Objectives: To describe outcomes of patients with early RA in a patient acceptable symptom state (PASS) at treatment initiation and to identify clusters of symptoms associated with poor outcomes.

Methods: Data came from the Rheumatoid Arthritis Medication Study, a UK multicentre cohort study of RA patients starting MTX. The HAQ, DAS28 and other patient-reported outcome measures (PROMs) were collected at baseline, and at 6 and 12 months. Patients answering yes to the question 'Is your current condition satisfactory, when you take your general functioning and your current pain into consideration?' were defined as PASS; patients answering no were defined as N-PASS. Symptom clusters in the baseline PASS group were identified using K-medians cluster analysis. Outcomes of baseline PASS vs N-PASS patients and each cluster are compared using random effects models.

Results: Of 1127 patients, 572 (50.8%) reported being in PASS at baseline. Over one year, baseline PASS patients had lower DAS28 (mean difference = -0.71, 95% CI -0.83, -0.59) and HAQ scores (mean difference = -0.48, 95% CI -0.56, -0.41) compared with N-PASS patients. Within the baseline PASS group, we identified six symptom clusters. Clusters characterized by high disease activity and high PROMs, or moderate disease activity and high PROMs, had the worst outcomes compared with the other clusters.

Conclusion: Despite reporting their condition as 'satisfactory', early RA patients with high PROM scores are less likely to respond to therapy. This group may require increased vigilance to optimize outcomes.
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http://dx.doi.org/10.1093/rheumatology/kez497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382599PMC
August 2020

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

Authors:
Polina Putrik Sofia Ramiro Francis Guillemin Márta Péntek Francisca Sivera Tuulikki Sokka Maarten de Wit Anthony D Woolf Angela Zink Daina Andersone Florian Berghea Irena Butrimiene Sandra Brouwer Karen Cassar Paraskevi Charalambous Roberto Caporali Elena Deseatnicova Nemanja S Damjanov Axel Finckh Oliver FitzGerald Gerður Gröndal Nino Gobejishjvili Piotr Gluszko Marco Hirsch Igor Jovanovic Jiří Vencovský Xavier Janssens Andras P Keszei Maria Kovarova Mart Kull Luís Cunha Miranda Miroslav Mayer Snezana Misevska-Percinkova Nevsun Inanc Oleg Nadashkevich Ingemar F Petersson Kari Puolakka Bernadette Rojkovich Helga Radner Fruzsina Szabados Gleb Slobodin Ivan Shirinsky Nikolay Soroka Prodromos Sidiropoulos Russka Shumnalieva Sekib Sokolovic Surayo Shukurova Argjend Tafaj Matija Tomšič Till Uhlig Suzanne M M Verstappen Annelies Boonen

Ann Rheum Dis 2019 11 19;78(11):1472-1479. Epub 2019 Aug 19.

Internal Medicine, Division of Rheumatology, Maastricht University, CAPHRI and Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.

Objectives: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries.

Methods: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates.

Results: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (β=-0.5 (95% CI -0.9 to -0.2) and β=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance.

Conclusions: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.
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http://dx.doi.org/10.1136/annrheumdis-2019-215294DOI Listing
November 2019

A UK study: vocational experiences of young adults with juvenile idiopathic arthritis.

Authors:
Laura E Lunt Ailsa Bosworth Matthew Bezzant Karen Walker-Bone Kimme L Hyrich Wendy Thomson Janet E McDonagh Suzanne M M Verstappen

Pediatr Rheumatol Online J 2019 08 6;17(1):54. Epub 2019 Aug 6.

Centre for Epidemiology Versus Arthritis, The University of Manchester, Manchester, UK.

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http://dx.doi.org/10.1186/s12969-019-0357-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683541PMC
August 2019

The predictors of and reasons for non-adherence in an observational cohort of patients with rheumatoid arthritis commencing methotrexate.

Authors:
Holly F Hope Kimme L Hyrich James Anderson James Bluett Jamie C Sergeant Anne Barton Lis Cordingley Suzanne M M Verstappen

Rheumatology (Oxford) 2020 01;59(1):213-223

NIHR Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Objective: In order to develop interventions to optimize MTX use for the treatment of RA we evaluated the rate of, reasons for and predictors of MTX non-adherence during the first 6 months of therapy.

Methods: The Rheumatoid Arthritis Medication Study (RAMS) is a prospective multicentre cohort study of incident MTX users in the UK. Prior to MTX commencement demographic, clinical and psychological data were collected. A weekly patient-completed diary recorded MTX dose, possible side effects and adherence over 26 weeks. The number of non-adherent weeks was calculated. Potential baseline predictors of ever non-adherence (⩾1 week non-adherent) during the first 6 months of MTX therapy were identified using logistic regression analyses.

Results: 606 patients with RA were included; 69% female, mean (s.d.) age 60 (13) years and DAS28 score 4.2 (1.2). Over the first 6 months following MTX initiation, 158 (26%) patients were ever non-adherent (71% intentional, 19% non-intentional, 10% unexplained) and mean (s.d.) number of non-adherent weeks was 2.5 (2.1). Multivariable predictors of ever non-adherence included DAS28 [odds ratios (OR) 1.1, 95% CI 1.0, 1.4], fatigue (OR 1.1, 95% CI 1.0, 1.2 per cm), ⩾2 comorbidities vs no comorbidities (OR 1.9, 95% CI 1.1, 3.5) and high medication concerns despite perceived need (OR 1.1, 95% CI 1.0, 1.1 per unit decrease in need/concern differential).

Conclusion: This is the largest study evaluating early intentional and non-intentional non-adherence to MTX, which has identified that patient beliefs and multi-morbidity strongly link with non-adherence. These findings can direct the design of and provide potential targets for interventions to improve patient adherence.
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http://dx.doi.org/10.1093/rheumatology/kez274DOI Listing
January 2020

Corrigendum to "Overview of changes in RMD epidemiology and outcome development in the last 10 years" [Best Pract Res Clin Rheumatol 32 (2018) 169-173].

Authors:
Suzanne M M Verstappen Loreto Carmona

Best Pract Res Clin Rheumatol 2018 Aug 7;32(4):618. Epub 2019 Feb 7.

Instituto de Salud Musculoesquel_etica, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.berh.2019.01.001DOI Listing
August 2018

Development and validation of a methotrexate adherence assay.

Authors:
James Bluett Isabel Riba-Garcia Suzanne M M Verstappen Thierry Wendling Kayode Ogungbenro Richard D Unwin Anne Barton

Ann Rheum Dis 2019 09 5;78(9):1192-1197. Epub 2019 Jun 5.

Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.

Background: The first-line therapy for rheumatoid arthritis (RA) is weekly oral methotrexate (MTX) at low dosages (7.5-25 mg/week). However, ~40% of patients are non-adherent which may explain why some do not respond and need to start more expensive biological therapies. To monitor adherence more accurately and develop strategies to improve it, a validated objective MTX adherence test is required.

Objective: To develop and validate the diagnostic accuracy of a novel MTX adherence assay using high-performance liquid chromatography-selected reaction monitoring- mass spectrometry (HPLC-SRM-MS) based biochemical analysis of drug levels.

Methods: 20 patients with RA underwent MTX pharmacokinetic assessment using HPLC-SRM-MS MTX plasma concentration analysis over a 6-day period. Directly observed therapy was the reference standard. Pharmacokinetic model validation was performed using independent plasma samples from real-world patients (n=50) with self-reported times of drug administration. Following assay optimisation, the sensitivity of the assay to detect adherence was established using samples from an observational cohort study (n=138).

Results: A two-compartment pharmacokinetic model was developed and validated. Simulations described the sensitivity required for MTX detection over 7 days; subsequent assay optimisation and retesting of samples confirmed that all patients were correctly identified as MTX adherers. Using real-world samples, the assays sensitivity was 95%.

Conclusion: Non-adherence to MTX is common and can have a significant effect on disease activity. HPLC-SRM-MS plasma analysis accurately detects MTX adherence. The validated objective test could easily be used in clinic to identify patients requiring adherence support.
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http://dx.doi.org/10.1136/annrheumdis-2019-215446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788879PMC
September 2019

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

Authors:
Yi Pan Sam Norton James M Gwinnutt Lianne Kearsley-Fleet Deborah P M Symmons Mark Lunt Adam Young Kimme L Hyrich Suzanne M M Verstappen

PLoS One 2019 20;14(5):e0215999. Epub 2019 May 20.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Background: United Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA.

Methods: The study included biologic-naïve patients receiving csDMARDs only with MDA (3.2
Results: In total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.

Conclusion: There is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215999PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527224PMC
January 2020

A Systematic Review of Productivity in Economic Evaluations of Workplace Interventions: A Need for Reporting Criteria?

Authors:
Cheryl Jones Suzanne M M Verstappen Katherine Payne

Appl Health Econ Health Policy 2019 10;17(5):591-613

Manchester Centre for Health Economics, The University of Manchester, 4.306, Jean McFarlane Building, Manchester, M13 9PL, UK.

Background: Rheumatic and musculoskeletal diseases (RMDs) are understood to reduce levels of paid productivity. Productivity, including absenteeism and presenteeism, is arguably an important factor for consideration in economic evaluations of workplace interventions for RMDs (WPI-RMDs). Existing methods available to quantify and value absenteeism and presenteeism are heterogeneous and produce estimates that vary substantially across studies. To date, there has been no systematic summary of the reporting quality of methods used to quantify paid productivity included in economic evaluations of WPI-RMDs.

Objective: The aim of this systematic review was twofold. First, the review was conducted to understand if, and how, the impact of WPI-RMDs on productivity was considered and incorporated in published economic evaluations. Second, we aimed to assess the reporting quality of productivity in published economic evaluations of WPI-RMDs and determine the need for a published set of reporting guidelines for productivity.

Methods: This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic review published in 2008 that focused on the cost effectiveness of WPIs, with limited information on productivity, was updated from 2007 to July 2018. A global search was conducted using three online databases: MEDLINE (1946 to August 2018, week 2), EMBASE (1974 to 10 July 2018); and EconLit (1886 to July 2018). The studies were double-screened by four independent reviewers. Data extraction was conducted using a bespoke data extraction table.

Results: Twenty-one economic evaluations of WPI-RMDs were identified. All studies evaluated absenteeism, but only five reported on levels of presenteeism. The methods used to identify and measure absenteeism were fairly consistent; however, methods used to identify and measure presenteeism, and value absenteeism and presenteeism, varied across studies. Two studies may have potentially double-counted productivity in their economic evaluations of WPI-RMDs. The results of this systematic review identified key elements potentially useful as a starting point to inform reporting quality guidelines for productivity.

Conclusions: Variation in the methods used to quantify productivity and how it is reported in economic evaluations suggests the need for specific published reporting guidelines for productivity. The development of standardised reporting guidelines for the identification, measurement, and valuation of absenteeism and presenteeism in economic evaluations may help reduce variation in the methods and promote transparency.
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http://dx.doi.org/10.1007/s40258-019-00473-8DOI Listing
October 2019

Considerations for Evaluating and Recommending Worker Productivity Outcome Measures: An Update from the OMERACT Worker Productivity Group.

Authors:
Suzanne M M Verstappen Diane Lacaille Annelies Boonen Reuben Escorpizo Catherine Hofstetter Ailsa Bosworth Amye Leong Sarah Leggett Monique A M Gignac Johan K Wallman Marieke M Ter Wee Florian Berghea Maria Agaliotis Peter Tugwell Dorcas Beaton

J Rheumatol 2019 10 1;46(10):1401-1405. Epub 2019 Apr 1.

From the Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre; UK National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester University Hospitals National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre, Manchester; Arthritis Research UK/Medical Research Council (MRC) Centre for Musculoskeletal Health and Work, University of Southampton, Southampton; National Rheumatoid Arthritis Society (NRAS), Maidenhead, UK; Department of Medicine, and the Division of Rheumatology, University of British Columbia, Vancouver; Arthritis Research Canada, Richmond, British Columbia; Institute for Work & Health; University of Toronto, Toronto; Division of Rheumatology, Department of Medicine, and School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Division of Rheumatology, Maastricht University Medical Center, Care and Public Health Research Institute (CAPHRI), Maastricht; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands; Department of Rehabilitation and Movement Science, University of Vermont, Burlington, Vermont, USA; Swiss Paraplegic Research, Nottwil, Switzerland; Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Rheumatology, Lund, Sweden; Carol Davila University of Medicine, Bucharest, Romania; School of Public Health and Community Medicine, University of New South Wales, Kensington, Australia.

Objective: The Outcome Measures in Rheumatology (OMERACT) Worker Productivity Group continues efforts to assess psychometric properties of measures of presenteeism.

Methods: Psychometric properties of single-item and dual answer multiitem scales were assessed, as well as methods to evaluate thresholds of meaning.

Results: Test-retest reliability and construct validity of single item global measures was moderate to good. The value of measuring both degree of difficulty and amount of time with difficulty in multiitems questionnaires was confirmed. Thresholds of meaning vary depending on methods and external anchors applied.

Conclusion: We have advanced our understanding of the performance of presenteeism measures and have developed approaches to describing thresholds of meaning.
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http://dx.doi.org/10.3899/jrheum.181201DOI Listing
October 2019

Comparing Proxy, Adolescent, and Adult Assessments of Functional Ability in Adolescents With Juvenile Idiopathic Arthritis.

Authors:
Stephanie J W Shoop-Worrall Kimme L Hyrich Suzanne M M Verstappen Jamie C Sergeant Eileen Baildam Alice Chieng Joyce Davidson Helen Foster Yiannis Ioannou Flora McErlane Lucy R Wedderburn Wendy Thomson Janet E McDonagh

Arthritis Care Res (Hoboken) 2020 04;72(4):517-524

Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, and University of Manchester, Manchester, UK.

Objective: In pediatric research, investigators rely on proxy reports of outcome, such as the proxy-completed Childhood Health Assessment Questionnaire (C-HAQ), to assess function in juvenile idiopathic arthritis (JIA). As children mature, they may self-complete the adult HAQ or the unvalidated adolescent-specific C-HAQ. It is unclear how these measures compare and whether they are directly interchangeable. The present study was undertaken to compare agreement between the proxy-completed C-HAQ, adolescent-specific C-HAQ, and the HAQ at initial presentation to pediatric rheumatologic care and 1 year following the first presentation in adolescents with JIA.

Methods: Adolescents ages 11-17 years participating in the Childhood Arthritis Prospective Study (CAPS), a UK multicenter inception cohort, were included. In a CAPS substudy, adolescents self-completed the adolescent-specific C-HAQ and the HAQ, and proxies simultaneously completed the proxy-completed C-HAQ at baseline and 1 year. Correlation and agreement between scores were assessed at baseline. Agreement and ability to similarly classify clinically important changes over time were assessed at 1 year following initial presentation to rheumatologic care.

Results: A total of 107 adolescents (adolescent-specific C-HAQ and HAQ) or their proxies (proxy-completed C-HAQ) had completed all 3 measures at baseline. Median age at diagnosis was 13 years, and 61% were female. Although the 3 scores demonstrated strong correlations (r > 0.8), they were not completely interchangeable, with agreement ranging between 70% and 80%. There was similar agreement between the changes in scores between baseline and 1 year. Using proxy-completed C-HAQ minimum clinically important cutoffs, the adolescent-specific C-HAQ and the HAQ similarly classified 80% to 90% of adolescents as having improved or worsened.

Conclusion: While there is relatively high agreement and similar classification of change between HAQ and the 2 C-HAQ scores, these are not completely interchangeable. This impacts the comparison of function when measured in different ways over the lifespan.
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http://dx.doi.org/10.1002/acr.23877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154708PMC
April 2020

Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis.

Authors:
Elizabeth M A Hensor Paul McKeigue Stephanie F Ling Marco Colombo Jennifer H Barrett Jackie L Nam Jane Freeston Maya H Buch Athina Spiliopoulou Felix Agakov Stephen Kelly Myles J Lewis Suzanne M M Verstappen Alexander J MacGregor Sebastien Viatte Anne Barton Costantino Pitzalis Paul Emery Philip G Conaghan Ann W Morgan

Rheumatology (Oxford) 2019 Mar 1. Epub 2019 Mar 1.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds.

Objectives: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis.

Methods: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients).

Results: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions.

Conclusion: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.
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http://dx.doi.org/10.1093/rheumatology/kez049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649844PMC
March 2019

Systematic review of the predictors of statin adherence for the primary prevention of cardiovascular disease.

Authors:
Holly F Hope George M Binkley Sally Fenton George D Kitas Suzanne M M Verstappen Deborah P M Symmons

PLoS One 2019 17;14(1):e0201196. Epub 2019 Jan 17.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester. England.

Introduction: Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention populations. Therefore the aim of this systematic review was to review predictors of statin adherence for the primary prevention of CVD.

Methods: A systematic search of papers published between Jan 1984 and May 2017 was conducted in PubMed, PsycINFO, EMbase and CINAHL databases. A study was eligible for inclusion if; 1) it was a study of the general population or of patients with familial hypercholesterolemia, hypertension, diabetes or arthritis; 2) statins were prescribed; 3) adherence was defined and measured as the extent to which patients followed their statin regimen during the period of prescription, and 4) it was an original trial or observational study (excluding case reports). A study was subsequently excluded if 1) results were not presented separately for primary prevention; 2) it was a trial of an intervention (for example patient education). Papers were reviewed by two researchers and consensus agreed with a third. A quality assessment (QA) tool was used to formally assess each included article. To evaluate the effect of predictors, data were quantitatively and qualitatively synthesised.

Results: In total 19 studies met the inclusion criteria and nine were evaluated as high quality using the QA tool. The proportion of patients classed as "adherent" ranged from 17.8% to 79.2%. Potential predictors of statin adherence included traditional risk factors for CVD such as age, being male, diabetes and hypertension. Income associated with adherence more strongly in men than women, and highly educated men were more likely and highly educated women less likely to be adherent. Alcohol misuse and high BMI associated with non-adherence. There was no association between polypharmacy and statin adherence. The evidence base for the effect of other lifestyle factors and health beliefs on statin adherence was limited.

Conclusion: Current evidence suggests that patients with more traditional risk factors for CVD are more likely to be adherent to statins. The implications for future research are discussed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336256PMC
September 2019

Overview of changes in RMD epidemiology and outcome development in the last 10 years.

Authors:
Suzanne M M Verstappen Loreto Carmona

Best Pract Res Clin Rheumatol 2018 04 17;32(2):169-173. Epub 2018 Nov 17.

Instituto de Salud Musculoesquelética, Madrid, Spain. Electronic address:

Epidemiological studies have been affected by environmental (or technological and societal) changes in the last 10 years, such as the emergence of registries, big data and machine learning algorithms, epigenetics, data protection regulations or a more solid presence of the patient perspective in outcomes research. As a consequence we, epidemiologists, are facing challenges in the design, conduct, and analysis of the studies, as well as on the interpretation of the results. Not everything that is new may be better than the old ways of doing epidemiology. In this article, we will review pros and cons of new technologies and regulations on epidemiological research, as well as ways to tackle obstacles and co-living of old and new methods.
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http://dx.doi.org/10.1016/j.berh.2018.10.008DOI Listing
April 2018

Epidemiology of rheumatic and musculoskeletal diseases.

Authors:
Suzanne M M Verstappen Loreto Carmona

Best Pract Res Clin Rheumatol 2018 04;32(2):167-168

Instituto de Salud Musculoesquelética, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.berh.2018.11.002DOI Listing
April 2018

Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis.

Authors:
Evo Alemao Maiwenn J Al Annelies A Boonen Matthew D Stevenson Suzanne M M Verstappen Kaleb Michaud Michael E Weinblatt Maureen P M H Rutten-van Mölken

PLoS One 2018 5;13(10):e0205013. Epub 2018 Oct 5.

Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.

The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework. A systematic literature review (SLR) of existing decision-analytic models was performed and analysis of an RA registry was conducted to inform the structure of the draft conceptual model. Finally, an expert panel was convened to seek input on the draft conceptual model. The proposed conceptual model consists of three separate modules: 1) patient characteristic module, 2) treatment module, and 3) outcome module. Consistent with the scope, the conceptual model proposed six changes to current economic models in RA. These changes proposed are to: 1) use composite measures of disease activity to evaluate treatment response as well as disease progression (at least two measures should be considered, one as the base case and one as a sensitivity analysis); 2) conduct utility mapping based on disease activity measures; 3) incorporate subgroups based on guideline-recommended prognostic factors; 4) integrate realistic treatment patterns based on clinical practice/registry datasets; 5) assimilate outcomes that are not joint related (extra-articular outcomes); and 6) assess mortality based on disease activity. We proposed a conceptual model that incorporates the current understanding of clinical and real-world evidence in RA, as well as of existing modeling assumptions. The proposed model framework was reviewed with experts and could serve as a foundation for developing future cost-effectiveness models in RA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205013PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173427PMC
March 2019

The prevalence of co-morbidities and their impact on physical activity in people with inflammatory rheumatic diseases compared with the general population: results from the UK Biobank.

Authors:
Michael J Cook Eftychia Bellou John Bowes Jamie C Sergeant Terence W O'Neill Anne Barton Suzanne M M Verstappen

Rheumatology (Oxford) 2018 12;57(12):2172-2182

Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal & Dermatological Sciences, Manchester, UK.

Objectives: To compare the prevalence and incidence of chronic co-morbidities in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), and to determine whether the prevalent co-morbidities are associated with physical activity levels in people with iRMDs and in those without iRMDs.

Methods: Participants were recruited to the UK Biobank; a population-based cohort. Data were collected about demographics, physical activity, iRMDs (RA, PsA, AS, SLE) and other chronic conditions, including angina, myocardial infarction, stroke, hypertension, pulmonary disease, diabetes and depression. The standardized prevalence of co-morbidities in people with iRMDs was calculated. Cox regression was used to determine the relationship between the presence of an iRMD and an incident co-morbidity. The relationship between the presence (versus absence) of a (co-)morbidity and physical activity level (low, moderate, high) in people with iRMDs and in those without was assessed using multinomial logistic regression.

Results: A total of 488 991 participants were included. The estimated prevalence of each co-morbidity was increased in participants with an iRMD, compared with in those without, particularly for stroke in participants with SLE (standardized morbidity ratio (95% CI), 4.9 (3.6, 6.6). Compared with people with no iRMD and no morbidity, the odds ratios (95% CI) for moderate physical activity were decreased for: no iRMD and morbidity, 0.87 (0.85, 0.89); iRMD and no co-morbidity, 0.71 (0.64, 0.80); and iRMD and co-morbidity, 0.58 (0.54, 0.63).

Conclusion: Having a (co-)morbidity is associated with reduced physical activity in the general population, and to a greater extent in participants with an iRMD. Optimal management of both iRMDs and co-morbidities may help to reduce their impact on physical activity.
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http://dx.doi.org/10.1093/rheumatology/key224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256331PMC
December 2018

Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS).

Authors:
Jamie C Sergeant Kimme L Hyrich James Anderson Kamilla Kopec-Harding Holly F Hope Deborah P M Symmons Anne Barton Suzanne M M Verstappen

Arthritis Res Ther 2018 07 13;20(1):147. Epub 2018 Jul 13.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.

Background: Methotrexate (MTX) remains the disease-modifying anti-rheumatic drug of first choice in rheumatoid arthritis (RA) but response varies. Predicting non-response to MTX could enable earlier access to alternative or additional medications and control of disease progression. We aimed to identify baseline predictors of non-response to MTX and combine these into a prediction algorithm.

Methods: This study included patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre prospective observational study of patients with RA or undifferentiated polyarthritis, commencing MTX for the first time. Non-response to MTX at 6 months was defined as "no response" using the European League Against Rheumatism (EULAR) response criteria, discontinuation of MTX due to inefficacy or starting biologic therapy. The association of baseline demographic, clinical and psychosocial predictors with non-response was assessed using logistic regression. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots.

Results: Of 1050 patients, 449 (43%) were classified as non-responders. Independent multivariable predictors of MTX non-response (OR (95% CI)) were rheumatoid factor (RF) negativity (0.62 (0.45, 0.86) for RF positivity versus negativity), higher Health Assessment Questionnaire score (1.64 (1.25, 2.15)), higher tender joint count (1.06 (1.02, 1.10)), lower Disease Activity score in 28 joints (0.29 (0.23, 0.39)) and higher Hospital Anxiety and Depression Scale anxiety score (1.07 (1.03, 1.12)). The optimism-corrected AUC was 0.74.

Conclusions: This is the first model for MTX non-response to be developed in a large contemporary study of patients commencing MTX in which demographic, clinical and psychosocial predictors were considered. Patient anxiety was a predictor of non-response and could be addressed at treatment commencement.
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http://dx.doi.org/10.1186/s13075-018-1645-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044018PMC
July 2018

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Authors:
John C Taylor Tim Bongartz Jonathan Massey Borbala Mifsud Athina Spiliopoulou Ian C Scott Jianmei Wang Michael Morgan Darren Plant Marco Colombo Peter Orchard Sarah Twigg Iain B McInnes Duncan Porter Jane E Freeston Jackie L Nam Heather J Cordell John D Isaacs Jenna L Strathdee Donna Arnett Maria J H de Hair Paul P Tak Stella Aslibekyan Ronald F van Vollenhoven Leonid Padyukov S Louis Bridges Costantino Pitzalis Andrew P Cope Suzanne M M Verstappen Paul Emery Michael R Barnes Felix Agakov Paul McKeigue Taisei Mushiroda Michiaki Kubo Richard Weinshilboum Anne Barton Ann W Morgan Jennifer H Barrett

Pharmacogenomics J 2018 07 25;18(4):528-538. Epub 2018 May 25.

Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
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http://dx.doi.org/10.1038/s41397-018-0025-5DOI Listing
July 2018

Baseline patient reported outcomes are more consistent predictors of long-term functional disability than laboratory, imaging or joint count data in patients with early inflammatory arthritis: A systematic review.

Authors:
James M Gwinnutt Charlotte A Sharp Deborah P M Symmons Mark Lunt Suzanne M M Verstappen

Semin Arthritis Rheum 2018 12 15;48(3):384-398. Epub 2018 Mar 15.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK. Electronic address:

Objective: To assess baseline predictors of long-term functional disability in patients with inflammatory arthritis (IA).

Methods: We conducted a systematic review of the literature from 1990 to 2017 using MEDLINE and EMBASE. Studies were included if (i) they were prospective observational studies, (ii) all patients had IA with symptom duration ≤2 years at baseline, (iii) follow-up was at least 5 years, and (iv) baseline predictors of HAQ score at long-term follow-up (i.e., ≥5 years following baseline) were assessed. Information on the included studies and estimates of the association between baseline variables and long-term HAQ scores were extracted from the full manuscripts.

Results: Of 1037 abstracts identified by the search strategy, 37 met the inclusion/exclusion criteria and were included in the review. Older age at baseline and female gender were reported to be associated with higher long-term HAQ scores in the majority of studies assessing these relationships, as were higher baseline HAQ and greater pain scores (total patients included in analyses reporting significant associations/total number of patients analysed: age 9.8k/10.7k (91.6%); gender 9.9k/11.3k (87.4%); HAQ 4.0k/4.0k (99.0%); pain 2.8k/2.9k (93.6%)). Tender joint count, erythrocyte sedimentation rate (ESR) and DAS28 were also reported to predict long-term HAQ score; other disease activity measures were less consistent (tender joints 2.1k/2.5k (84.5%); erythrocyte sedimentation rate 1.6k/2.2k (72.3%); DAS28 888/1.1k (79.2%); swollen joints 684/2.6k (26.6%); C-reactive protein 279/510 (54.7%)). Rheumatoid factor (RF) and erosions were not useful predictors (RF 546/4.6k (11.9%); erosions 191/2.7k (7.0%)), whereas the results for anti-citrullinated protein antibody positivity were equivocal (ACPA 2.0k/3.8k (52.9%)).

Conclusions: Baseline age, gender, HAQ and pain scores are associated with long-term disability and knowledge of these may aid the assessment of prognosis.
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http://dx.doi.org/10.1016/j.semarthrit.2018.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562164PMC
December 2018

Long-Term Outcomes Following Achievement of Clinically Inactive Disease in Juvenile Idiopathic Arthritis: The Importance of Definition.

Authors:
Stephanie J W Shoop-Worrall Suzanne M M Verstappen Janet E McDonagh Eileen Baildam Alice Chieng Joyce Davidson Helen Foster Yiannis Ioannou Flora McErlane Lucy R Wedderburn W Thomson Kimme L Hyrich

Arthritis Rheumatol 2018 09 22;70(9):1519-1529. Epub 2018 Jul 22.

The University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Objective: Potential targets for treat-to-target strategies in juvenile idiopathic arthritis are minimal disease activity (MDA) and clinically inactive disease (CID). We undertook this study to compare short- and long-term outcomes following achievement of MDA and CID on the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et al's preliminary criteria.

Methods: Children recruited to the Childhood Arthritis Prospective Study, a UK multicenter inception cohort, were selected if they were recruited prior to January 2011 and diagnosed as having oligoarthritis or rheumatoid factor-negative or -positive polyarthritis. One year following diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both Wallace et al's preliminary criteria and the cJADAS10. Associations were tested between those disease states and functional ability, absence of joints with limited range of motion, psychosocial health, and pain at 1 year and annually to 5 years.

Results: Of 832 children, 70% were female and the majority had oligoarthritis (68%). At 1 year, 21% had achieved CID according to both definitions, 7% according to Wallace et al's preliminary criteria alone, and 16% according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children in the entire cohort achieved MDA without also achieving CID. Achieving either early CID state was associated with a greater absence of joints with limited range of motion. However, only CID according to the cJADAS10 was associated with improved functional ability and psychosocial health. Achieving CID was superior to achieving MDA in terms of short- and long-term pain and the absence of joints with limited range of motion.

Conclusion: CID on the cJADAS10 may be preferable as a treatment target to CID on Wallace et al's preliminary criteria in terms of both feasibility of application and long-term outcomes.
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http://dx.doi.org/10.1002/art.40519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175118PMC
September 2018

Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study.

Authors:
James Bluett Jamie C Sergeant Alex J MacGregor Jacqueline R Chipping Tarnya Marshall Deborah P M Symmons Suzanne M M Verstappen

Arthritis Res Ther 2018 03 20;20(1):50. Epub 2018 Mar 20.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.

Background: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure.

Methods: Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks.

Results: A total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort.

Conclusions: RF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.
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http://dx.doi.org/10.1186/s13075-018-1544-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859656PMC
March 2018

Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register.

Authors:
James M Gwinnutt Deborah P M Symmons Alexander J MacGregor Jacqueline R Chipping Tarnya Marshall Mark Lunt Suzanne M M Verstappen

Ann Rheum Dis 2018 06 23;77(6):848-854. Epub 2018 Feb 23.

Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Objective: To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart.

Methods: Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression.

Results: In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI -23% to -10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24).

Conclusion: Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.
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http://dx.doi.org/10.1136/annrheumdis-2017-212426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965352PMC
June 2018

Comparison of the risks of hospitalisation for cardiovascular events in patients with rheumatoid arthritis treated with tocilizumab and etanercept.

Authors:
Elena Generali Greta Carrara Carlo Selmi Suzanne M M Verstappen Antonella Zambon Alessandra Bortoluzzi Ettore Silvagni Carlo Alberto Scirè

Clin Exp Rheumatol 2018 Mar-Apr;36(2):310-313. Epub 2017 Dec 28.

Epidemiology Unit, Italian Society for Rheumatology, Milan; and Rheumatology Unit, Department of Medical Sciences, University of Ferrara, Italy.

Objectives: To verify if tocilizumab (TCZ) is associated with an increased risk of cardiovascular (CV) events compared with etanercept (ETN) in rheumatoid arthritis (RA).

Methods: This is a retrospective cohort study on administrative healthcare databases (AHD) in Italy. Patients were identified using a validated algorithm based on AHD. Exposure to specific drugs was estimated by the drug prescription recorded in the AHD. The occurrence of acute CV events (myocardial infarction, stroke, other CV events) was derived from the hospital discharge forms. The association between TCZ or ETN and CV events was estimated using competing risk models, adjusting for pre-specified confounders.

Results: We identified 1,752 subjects with RA, 1,086 treated with ETN and 666 with TCZ. TCZ did not increase the overall risk of acute CV events, even when adjusted for pre-specified confounders (hazard ratio HR 0.95, 95% confidence interval 95%CI 0.54-1.66), specifically of acute myocardial infarction (HR 0.39, 95%CI 0.15-1.06), stroke (HR 1.44, 95%CI 0.24-8.68) or other CV event (1.07, 95%CI 0.59-1.92).

Conclusions: RA patients with TCZ do not have a medium-term excess of CV risk in patients compared with ETN.
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June 2018

Patterns of pain over time among children with juvenile idiopathic arthritis.

Authors:
Amir Rashid Lis Cordingley Roberto Carrasco Helen E Foster Eileen M Baildam Alice Chieng Joyce E Davidson Lucy R Wedderburn Yiannis Ioannou Flora McErlane Suzanne M M Verstappen Kimme L Hyrich Wendy Thomson

Arch Dis Child 2018 05 25;103(5):437-443. Epub 2017 Nov 25.

NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Objectives: Pain is a very common symptom of juvenile idiopathic arthritis (JIA). Disease activity alone cannot explain symptoms of pain in all children, suggesting other factors may be relevant. The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain.

Methods: This study used longitudinal-data from patients (aged 1-16 years) with new-onset JIA. Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospective Study (CAPS) were used. A two-step approach was adopted. First, pain trajectories were modelled using a discrete mixture model. Second, multinomial logistic regression was used to determine the association between variables and trajectories.

Results: Data from 851 individuals were included (4 years, median follow-up). A three-group trajectory model was identified: consistently low pain (n=453), improved pain (n=254) and consistently high pain (n=144). Children with improved pain or consistently high pain differed on average at baseline from consistently low pain. Older age at onset, poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain. Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain.

Conclusions: This study has identified routinely collected clinical factors, which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease. Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes.
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http://dx.doi.org/10.1136/archdischild-2017-313337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916104PMC
May 2018

Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme.

Authors:
Hisashi Yamanaka Johan Askling Niklas Berglind Stefan Franzen Thomas Frisell Christopher Garwood Jeffrey D Greenberg Meilien Ho Marie Holmqvist Laura Novelli Horne Eisuke Inoue Kaleb Michaud Dimitrios A Pappas George Reed Deborah Symmons Eiichi Tanaka Trung N Tran Suzanne M M Verstappen Eveline Wesby-van Swaay Fredrik Nyberg

RMD Open 2017 10;3(2):e000498. Epub 2017 Oct 10.

Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population.

Methods: We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score.

Results: Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14-1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86-2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99-2.84, trials rate 2.74).

Conclusion: This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries.
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http://dx.doi.org/10.1136/rmdopen-2017-000498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652583PMC
October 2017