Publications by authors named "Jessica A Walsh"

54 Publications

Muscle stimulation in advanced idiopathic pulmonary fibrosis: a randomised placebo-controlled feasibility study.

BMJ Open 2021 06 2;11(6):e048808. Epub 2021 Jun 2.

Harefield Respiratory Research Group, Royal Brompton and Harefield Clinical Group, Guy's and St Thomas' Hospitals NHS Trust, London, UK.

Objectives: To assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible.

Design: A randomised, parallel, two-group, participant and assessor-blinded, placebo-controlled feasibility trial with embedded qualitative interviews.

Setting: Outpatient department, Royal Brompton and Harefield Hospitals.

Participants: Twenty-two people with IPF: median (25th, 75th centiles) age 76 (74, 82) years, forced vital capacity 62 (50, 75) % predicted, 6 min walk test distance 289 (149, 360) m.

Interventions: Usual care (home-based exercise, weekly telephone support, breathlessness management leaflet) with either placebo or active NMES for 6 weeks, with follow-up at 6 and 12 weeks.

Primary Outcome Measures: Feasibility of recruitment and retention, treatment uptake and adherence, outcome assessments, participant and outcome assessor blinding and adverse events related to interventions.

Secondary Outcome Measures: Outcome measures with potential to be primary or secondary outcomes in a definitive clinical trial. In addition, purposively sampled participants were interviewed to capture their experiences and acceptability of the trial.

Results: Out of 364 people screened, 23 were recruited: 11 were allocated to each group and one was withdrawn prior to randomisation. Compared with the control group, a greater proportion of the intervention group completed the intervention, remained in the trial blinded to group allocation and experienced intervention-related adverse events. Assessor blinding was maintained. The secondary outcome measures were feasible with most missing data associated with the accelerometer. Small participant numbers precluded identification of an outcome measure suitable for a definitive trial. Qualitative findings demonstrated that trial process and active NMES were acceptable but there were concerns about the credibility of placebo NMES.

Conclusions: Primarily owing to recruitment difficulties, a definitive trial using the current protocol to evaluate NMES in people with IPF is not feasible.

Trial Registration Number: NCT03499275.
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http://dx.doi.org/10.1136/bmjopen-2021-048808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174518PMC
June 2021

Expert consensus on the operation of an adult tertiary intellectual disability mental health service in New South Wales, Australia.

Australas Psychiatry 2021 May 16:10398562211014228. Epub 2021 May 16.

Department of Developmental Disability Neuropsychiatry, School of Psychiatry, UNSW Sydney, Sydney, NSW, Australia.

Objective: To identify and reach consensus on the priorities and operation of an adult tertiary intellectual disability mental health service in New South Wales, Australia.

Method: An online Delphi consultation was conducted with 25 intellectual disability mental health experts.

Results: Participants agreed that the service should involve a multidisciplinary team and accept people with an intellectual disability aged over 15 years with complex needs and/or atypical presentations. Agreed service roles included short-term assessment, diagnosis and treatment, providing high-level clinical advice, and capacity building. Endorsed principles and practical ways of working align with existing guidelines.

Conclusions: This study describes experts' views on how an adult tertiary intellectual disability mental health service should operate in New South Wales. Further consultation is needed to determine the views of people with an intellectual disability and mental health staff.
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http://dx.doi.org/10.1177/10398562211014228DOI Listing
May 2021

Gait speed and adverse outcomes following hospitalised exacerbation of COPD.

Eur Respir J 2021 Apr 29. Epub 2021 Apr 29.

Harefield Respiratory Research Group, Royal Brompton & Harefield Hospitals, Guy's and St.Thomas' NHS Foundation Trust, London, UK.

Four-metre gait speed (4MGS) is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of COPD (AECOPD).213 participants hospitalised with AECOPD (52% male, mean age and FEV, 72 years and 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 y after discharge, and multivariable Cox-proportional hazards regression were performed. Kaplan-Meier and Competing risk analysis was conducted comparing time to all-cause readmission and mortality between 4MGS quartiles.111 participants (52%) were readmitted, and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797-0.945; p=0.001) per 0.1 m·s increase in gait speed, and with all-cause mortality with an adjusted subdistribution hazard ratio of 0.747 (95% CI: 0.622-0.898; p=0.002) per 0.1 m·s increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV% predicted alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80 respectively. Kaplan-Meier and Competing Risk curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log rank both p<0.001).4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support.
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http://dx.doi.org/10.1183/13993003.04047-2020DOI Listing
April 2021

Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the Model Using Accelerated Experience-Based Co-Design.

Int J Chron Obstruct Pulmon Dis 2021;16:1035-1049. Epub 2021 Apr 19.

School of Health Sciences, University of East Anglia, Norwich, UK.

Background: Hospital at home (HaH) schemes allow early discharge of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Traditional outpatient pulmonary rehabilitation (PR) following an AECOPD has an established evidence-base, but there are issues with low referral, uptake and completion. One commonly cited barrier to PR post-hospitalisation relates to poor accessibility. To address this, the aim of this project was to enrol service users (patients with COPD and informal carers) and healthcare professionals to co-design a model of care that integrates home-based exercise training within a HaH scheme for patients discharged from hospital following AECOPD.

Methods: This accelerated experience-based co-design project included three audio-recorded stakeholder feedback events, using key "touchpoints" from previous qualitative interviews and a recent systematic review. Audio-recordings were inductively analysed using directed content analysis. An integrated model of care was then developed and finalised through two co-design groups, with the decision-making process facilitated by the tables of changes approach.

Results: Seven patients with COPD, two informal carers and nine healthcare professionals (from an existing outpatient PR service and HaH scheme) participated in the stakeholder feedback events. Four key themes were identified: 1) individualisation, 2) progression and transition, 3) continuity between services, and 4) communication between stakeholders. Two patients with COPD, one informal carer and three healthcare professionals participated in the first joint co-design group, with five healthcare professionals attending a second co-design group. These achieved a consensus on the integrated model of care. The agreed model comprised face-to-face supervised, individually tailored home-based exercise training one to three times a week, delivered during HaH scheme visits where possible by a healthcare professional competent to provide both home-based exercise training and usual HaH care.

Conclusion: An integrated model of care has been co-designed by patients with COPD, informal carers and healthcare professionals to address low uptake and completion of PR following AECOPD. The co-designed model of care has now been integrated within a well-established HaH scheme.
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http://dx.doi.org/10.2147/COPD.S293048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064617PMC
July 2021

Psoriasis Characteristics for the Early Detection of Psoriatic Arthritis.

J Rheumatol 2021 Apr 15. Epub 2021 Apr 15.

This study was partially supported by the 2019 Discovery Research Grant and Psoriatic Arthritis Diagnostic Test Grant from the National Psoriasis Foundation, the 2018 Immunology, Inflammation, and Infectious Diseases 3i Initiative at the University of Utah, and Pfizer Inc. (grant numbers WI227108 and WI240276). The support and resources from the Center for High-Performance Computing at the University of Utah are gratefully acknowledged. The computational resources used were partially funded by the National Institutes of Health (NIH) Shared Instrumentation Grant 1S10OD021644-01A1. This project utilized REDCap at the University of Utah, supported by grant 8UL1TR000105 ( formerly UL1RR025764) from the National Center for Advancing Translational Sciences and NIH. S. Belman, MSc, School of Medicine, University of Utah, Salt Lake City, Utah, USA, and Wellcome Sanger Institute, University of Cambridge, Hinxton, UK; J.A. Walsh, MD, C. Carroll, MSc, M. Milliken, MD, MPH, K. Callis Duffin, MD, G.G. Krueger, MD, School of Medicine, University of Utah, Salt Lake City, Utah, USA; B. Haaland, PhD, B.J. Feng, PhD, School of Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. The PERCH software, for which BJF is the inventor, has been nonexclusively licensed to Ambry Genetics Corporation for their clinical genetic testing services and research. BJF also reports funding and sponsorship to his institution on his behalf from Pfizer Inc., Regeneron Genetics Center LLC., and AstraZeneca. BH has consulted for the National Kidney Foundation and Value Analytics Labs. The remaining authors declare no potential conflicts of interest relevant to this article. Address correspondence to Dr. B.J. Feng, 30 N 1900 E, Department of Dermatology, Salt Lake City, UT 84132, USA. Email: Accepted for publication March 29, 2021.

Objective: Delays in the diagnosis and treatment of psoriatic arthritis (PsA) are common. These delays contribute to impairments in quality of life and joint damage. This study aims to calculate the incidence rate of PsA over time and identify clinical features that may be used for PsA prediction in patients with psoriasis (PsO).

Methods: The study population for PsA incidence analysis included 1128 participants enrolled in the Utah Psoriasis Initiative between 2002 and 2014. Clinical evaluation and medical record review were performed to identify new cases of PsA after enrollment. To identify PsO features associated with PsA, the population was restricted to 627 participants who did not have PsA before PsO phenotyping and had been followed up for subsequent PsA diagnosis. We conducted Cox proportional hazard regressions to estimate the HR of PsA associated with PsO characteristics and other health-related features.

Results: PsA incidence rate increased for > 60 years following PsO onset (trend < 0.0001). There was a significant association between PsA and induration severity in untreated lesions ( < 0.001, HR 1.46), history of fingernail involvement ( < 0.001, HR 2.38), pustular PsO ( < 0.001, HR 3.32), fingernail involvement at enrollment ( < 0.001, HR 2.04), and Koebner phenomenon ( < 0.001, HR 1.90). Multivariate analysis yielded a model that included a history of fingernail involvement ( < 0.001, HR 2.16) and untreated induration ( < 0.001, HR 1.41).

Conclusion: Risk of PsA increases steadily for > 60 years following PsO onset. Patient-reported history of PsO characteristics has greater predictive power than physician-measured features at enrollment visits. The characteristics identified in this study provide guidance for screening for PsA risk in patients with PsO.
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http://dx.doi.org/10.3899/jrheum.201123DOI Listing
April 2021

Minimal clinically important difference for daily pedometer step count in COPD.

ERJ Open Res 2021 Jan 22;7(1). Epub 2021 Mar 22.

Harefield Respiratory Research Group, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK.

https://bit.ly/3ci97Jh.
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http://dx.doi.org/10.1183/23120541.00823-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983253PMC
January 2021

Treatment Persistence and Adherence Among Patients With Psoriatic Arthritis Who Initiated Targeted Immune Modulators in the US: A Retrospective Cohort Study.

Adv Ther 2021 05 23;38(5):2353-2364. Epub 2021 Mar 23.

Janssen Scientific Affairs, LLC, Immunology Medical Affairs, Horsham, PA, USA.

Introduction: This study compared treatment persistence and adherence among psoriatic arthritis (PsA) patients in the US who initiated an interleukin-12/23 inhibitor (IL-12/23i) versus those who initiated tumor necrosis factor inhibitors (TNFis), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), or interleukin-17 inhibitors (IL-17is).

Methods: Adults diagnosed with PsA with ≥ 1 claim for a targeted immune modulator were selected from the IBM MarketScan Commercial and Medicare Supplemental databases (October 1, 2013-October 31, 2018). The date of the first claim was the index date. Patients had continuous health plan enrollment for ≥ 12 months pre-index and ≥ 12-month post-index period. Pairwise propensity score matching with nearest-neighbor technique was performed. Persistence duration, discontinuation rate, and the proportion of days covered (PDC) were evaluated in biologic/tsDMARD naïve patients who initiated TNFis, IL-17is, tsDMARDs, or IL-12/23i (reference group).

Results: There were 238 matched patient pairs for TNFi versus IL-12/23i, 238 pairs for tsDMARD versus IL-12/23i, and 189 pairs for IL-17is versus IL-12/23i. Duration of persistence was longer for the IL-12/23i cohort than for the TNFi (269 vs. 215 days, p < 0.001) or tsDMARD (269 vs. 213 days, p < 0.001) cohorts, but comparable between the IL-12/23i and IL-17i cohorts (267 vs. 246 days, p = 0.199). Fewer patients in the IL-12/23i cohort discontinued their index medication than in the TNFi (53.4% vs. 73.9%, p < 0.001) or tsDMARD (53.4% vs. 71.8%, p < 0.001) cohorts, but no significant difference was observed between the IL-12/23i and IL-17i cohorts (52.9% vs. 58.2%, p = 0.288). During the 12-month follow-up, adherence (i.e., PDC) was higher among those who initiated an IL-12/23i than among those who initiated TNFis (0.64 vs. 0.56, p = 0.004) or tsDMARDs (0.64 vs. 0.58, p = 0.027), but similar to those who initiated IL-17is (0.64 vs. 0.65, p = 0.589).

Conclusion: In this real-world study of PsA therapies with differing mechanisms of action, the IL-12/23i demonstrated longer persistence and higher adherence than either TNFis or tsDMARDs, and comparability to IL-17is.
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http://dx.doi.org/10.1007/s12325-021-01687-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107156PMC
May 2021

The effect of intravenous golimumab on health-related quality of life and work productivity in patients with active psoriatic arthritis: results of the Phase 3 GO-VIBRANT trial.

Clin Rheumatol 2021 Mar 2. Epub 2021 Mar 2.

Cleveland Clinic, Cleveland, OH, USA.

Introduction/objectives: To evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).

Methods: Patients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.

Results: At Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (-2.91 vs -0.71), and WLQ productivity loss score (-2.92 vs -0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: -2.89 and -3.31; WLQ productivity loss: -4.49 and -3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.

Conclusion: IV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability. Key Points • In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes • IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity.
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http://dx.doi.org/10.1007/s10067-021-05639-1DOI Listing
March 2021

COPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPD.

Thorax 2021 Mar 2. Epub 2021 Mar 2.

Harefield Respiratory Research Group, Royal Brompton & Harefield Hospitals, Guy's and St.Thomas' NHS Foundation Trust, London, UK.

Pulmonary rehabilitation (PR) following hospitalisations for acute exacerbation of COPD (AECOPD) is associated with improved exercise capacity and quality of life, and reduced readmissions. However, referral for, and uptake of, post-hospitalisation PR are low. In this prospective cohort study of 291 consecutive hospitalisations for AECOPD, COPD discharge bundles delivered by PR practitioners compared with non-PR practitioners were associated with increased PR referral (60% vs 12%, p<0.001; adjusted OR: 14.46, 95% CI: 5.28 to 39.57) and uptake (40% vs 32%, p=0.001; adjusted OR: 8.60, 95% CI: 2.51 to 29.50). Closer integration between hospital and PR services may increase post-hospitalisation PR referral and uptake.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215464DOI Listing
March 2021

A comparison of physical function instruments in psoriatic arthritis: HAQ-DI vs MDHAQ vs PROMIS10 global physical health.

Rheumatology (Oxford) 2021 05;60(5):2307-2316

Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Objectives: Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10.

Methods: Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20.

Results: A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively.

Conclusion: The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.
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http://dx.doi.org/10.1093/rheumatology/keaa591DOI Listing
May 2021

Identifying Patients With Axial Spondyloarthritis in Large Datasets: Expanding Possibilities for Observational Research.

J Rheumatol 2021 May 1;48(5):685-692. Epub 2020 Sep 1.

J.A. Walsh, MD, MBA, MSCI, S. Pei, PhD, R.S. Overbury, MD, B.C. Sauer, PhD, G.K. Penmetsa, MD, D.O. Clegg, MD, Salt Lake City Veterans Affairs and University of Utah Medical Centers, Department of Internal Medicine, Divisions of Rheumatology and Epidemiology, Salt Lake City, Utah, USA.

Objective: Observational research of axial spondyloarthritis (axSpA) is limited by a lack of methods for identifying diverse axSpA phenotypes in large datasets. Algorithms were previously designed to identify a broad spectrum of patients with axSpA, including patients not identifiable with diagnosis codes. The study objective was to estimate the performance of axSpA identification methods in the general Veterans Affairs (VA) population.

Methods: A patient sample with known axSpA status (n = 300) was established with chart review. For feasibility, this sample was enriched with veterans with axSpA risk factors. Algorithm performance outcomes included sensitivities, positive predictive values (PPV), and F1 scores (an overall performance metric combining sensitivity and PPV). Performance was estimated with unweighted outcomes for the axSpA-enriched sample and inverse probability weighted (IPW) outcomes for the general VA population. These outcomes were also assessed for traditional identification methods using diagnosis codes for the ankylosing spondylitis (AS) subtype of axSpA.

Results: The mean age was 54.7 and 92% were male. Unweighted F1 scores (0.59-0.74) were higher than IPW F1 scores (0.48-0.65). The full algorithm had the best overall performance (F1 0.65). The Early Algorithm was the most inclusive (sensitivity 0.90, PPV 0.38). The traditional method using ≥ 2 AS diagnosis codes from rheumatology had the highest PPV (PPV 0.84, sensitivity 0.34).

Conclusion: The axSpA identification methods demonstrated a range of performance attributes in the general VA population that may be appropriate for various types of studies. The novel identification algorithms may expand the scope of research by enabling identification of more diverse axSpA populations.
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http://dx.doi.org/10.3899/jrheum.200570DOI Listing
May 2021

Clinical Manifestations and Diagnosis of Axial Spondyloarthritis.

J Clin Rheumatol 2020 Oct 22. Epub 2020 Oct 22.

The MetroHealth System and School of Medicine, Case Western Reserve University, Cleveland, OH.

Background: Axial spondyloarthritis (axSpA) is a chronic, rheumatic disease characterized by inflammation of the sacroiliac joint, spine, and entheses. Axial spondyloarthritis affects up to 1.4% of adults in the United States and is associated with decreased quality of life, increased mortality, and substantial health care-related costs, imposing a high burden on patients, their caregivers, and society.

Summary Of Work: Diagnosing axSpA can be difficult. In this review, we seek to help rheumatologists in recognizing and diagnosing axSpA.

Major Conclusions: A discussion of challenges associated with diagnosis is presented, including use and interpretation of imaging, reasons for diagnostic delays, differences in disease presentation by sex, and differential diagnoses of axSpA.

Future Research Directions: The early diagnosis of axSpA and advances in available therapeutic options have improved patient care and disease management, but delays in diagnosis and treatment remain common. Additional research and education are critical for recognizing diverse axSpA presentations and optimizing management early in the course of disease.
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http://dx.doi.org/10.1097/RHU.0000000000001575DOI Listing
October 2020

Ixekizumab Improves Functioning and Health in the Treatment of Active Non-Radiographic Axial Spondyloarthritis: 52-Week Results, COAST-X Trial.

Arthritis Care Res (Hoboken) 2020 Oct 12. Epub 2020 Oct 12.

Rheumazentrum Ruhrgebiet, Herne, Germany.

Objective: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active non-radiographic axial spondyloarthritis (nr-axSpA).

Methods: COAST-X is a randomized, controlled trial conducted in patients with nr-axSpA of 52-weeks duration. Participants were randomized 1:1:1 to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo for 52 Weeks. Self-reported functioning and health endpoints included the Medical Outcomes Study 36-Item Short Form Health Survey 36-item (SF-36), Assessment of SpondyloArthritis international Society Health Index (ASAS HI), and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility.

Results: Compared with placebo, ixekizumab treatment improved SF-36 Physical Component Summary scores from baseline (4.7 versus 8.9 IXE Q4W, p<0.05, 9.3 IXE Q2W, p<0.01), with greatest improvements observed in Physical Functioning, Role-physical and Bodily Pain domains at Weeks 16 and 52. Higher proportion of patients receiving ixekizumab reported ASAS HI improvements ≥3 from baseline at Weeks 16 (Q2W, p<0.05) and 52 (p<0.05). Significantly more patients on ixekizumab reported improvements in ASAS HI "good health status" (ASAS HI ≤5) at Weeks 16 (Q4W, p<0.05) and 52 (p<0.05). Patients on ixekizumab reported improvements in EQ-5D-5L versus placebo at Week 16 (0.11 versus 0.17 Q4W, 0.19 Q2W, p<0.05), which remained consistent at Week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen (Q2W or Q4W).

Conclusion: Ixekizumab was superior to placebo improving self-reported functioning and health in patients with nr-axSpA at Weeks 16 and 52.
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http://dx.doi.org/10.1002/acr.24482DOI Listing
October 2020

Recognizing Axial Spondyloarthritis: A Guide for Primary Care.

Mayo Clin Proc 2020 11 29;95(11):2499-2508. Epub 2020 Jul 29.

University of Utah and Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.

Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: ["axSpA" OR "axial SpA" OR "axial spondyloarthritis" OR "ankylosing spondylitis"]) in combination with terms related to IBP ("inflammatory back pain" OR "IBP" OR "chronic back pain" OR "CBP" OR "lower back pain" OR "LBP"), diagnosis (["diagn∗" OR "classification"] AND ["criteria" OR "recommend∗" OR "guidelines"]), and referral ("refer∗"). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation.
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http://dx.doi.org/10.1016/j.mayocp.2020.02.007DOI Listing
November 2020

Ixekizumab Improves Functioning and Health in the Treatment of Radiographic Axial Spondyloarthritis: Week 52 Results from 2 Pivotal Studies.

J Rheumatol 2021 02 15;48(2):188-197. Epub 2020 Jul 15.

U. Kiltz, MD, J. Braun, MD, PhD, Rheumazentrum Ruhrgebiet, Herne, and Ruhr-Universität Bochum, Bochum, Germany.

Objective: This study evaluated the effect of ixekizumab (IXE) on self-reported functioning and health in patients with radiographic axial spondyloarthritis (r-axSpA) who were either biological disease-modifying antirheumatic drug (bDMARD)-naïve or failed at least 1 tumor necrosis factor inhibitor (TNFi).

Methods: In 2 multicenter, randomized, double-blind, placebo-controlled, and active-controlled (bDMARD-naïve only) trials, patients with r-axSpA were randomly assigned to receive 80 mg of IXE [every 2 weeks (Q2W) or every 4 weeks (Q4W)], placebo (PBO), or adalimumab (ADA; bDMARD-naïve only). After 16 weeks, patients who received PBO or ADA were rerandomized to receive IXE (Q2W or Q4W) up to Week 52. Functioning and health were measured by the generic 36-item Short Form Health Survey (SF-36) and the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI). Societal health utility was assessed by the 5-level EuroQol-5 Dimension (EQ-5D-5L).

Results: At Week 16, both doses of IXE in bDMARD-naïve and TNFi-experienced patients resulted in larger improvement in SF-36, ASAS HI, and EQ-5D-5L versus placebo. For SF-36, the largest improvements were seen for the domains of bodily pain, physical function, and role physical. A larger proportion of patients reaching improvement in ASAS HI ≥ 3 as well as an achievement of ASAS HI good health status was reported in patients treated with IXE. Improvements were maintained through Week 52.

Conclusion: IXE significantly improved functioning and health as assessed by both generic and disease-specific measures, as well as societal health utility values in patients with r-axSpA, as measured by SF-36, ASAS HI, and EQ-5D-5L at Week 16, and improvements were sustained through 52 weeks.
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http://dx.doi.org/10.3899/jrheum.200093DOI Listing
February 2021

Digital habits of PR service-users: Implications for home-based interventions during the COVID-19 pandemic.

Chron Respir Dis 2020 Jan-Dec;17:1479973120936685

Harefield Respiratory Research Group, Royal Brompton & Harefield NHS Foundation Trust, UK.

Remote models of pulmonary rehabilitation (PR) are vital with suspension of face-to-face activity during the COVID-19 pandemic. We surveyed digital access and behaviours and PR delivery preferences of current PR service users. There was significant heterogeneity in access to and confidence in using the Internet with 31% having never previously accessed the Internet, 48% confident using the Internet and 29% reporting no interest in accessing any component of PR through a Web-based app. These data have implications for the remote delivery of PR during the COVID-19 pandemic and raise questions about the current readiness of service users to adopt Web-based delivered models of PR.
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http://dx.doi.org/10.1177/1479973120936685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328358PMC
July 2020

Anxiety and depression in bronchiectasis: Response to pulmonary rehabilitation and minimal clinically important difference of the Hospital Anxiety and Depression Scale.

Chron Respir Dis 2020 Jan-Dec;17:1479973120933292

Harefield Respiratory Research Group, Royal Brompton and Harefield NHS Foundation Trust, Harefield, UK.

The aims of the study were to evaluate the responsiveness of Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale and HADS-Depression (HADS-D) subscale to pulmonary rehabilitation (PR) in patients with bronchiectasis compared to a matched group of patients with chronic obstructive pulmonary disease (COPD) and provide estimates of the minimal clinically important difference (MCID) of HADS-A and HADS-D in bronchiectasis. Patients with bronchiectasis and at least mild anxiety or depression (HADS-A ≥ 8 or/and HADS-D ≥ 8), as well as a propensity score-matched control group of patients with COPD, underwent an 8-week outpatient PR programme (two supervised sessions per week). Within- and between-group changes were calculated in response to PR. Anchor- and distribution-based methods were used to estimate the MCID. HADS-A and HADS-D improved in response to PR in both patients with bronchiectasis and those with COPD (median (25th, 75th centile)/mean (95% confidence interval) change: HADS-A change: bronchiectasis -2 (-5, 0), COPD -2 (-4, 0); = 0.43 and HADS-D change: bronchiectasis -2 (-2 to -1), COPD -2 (-3 to -2); = 0.16). Using 26 estimates, the MCID for HADS-A and HADS-D was -2 points. HADS-A and HADS-D are responsive to PR in patients with bronchiectasis and symptoms of mood disorder, with an MCID estimate of -2 points.
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http://dx.doi.org/10.1177/1479973120933292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301664PMC
July 2021

Real-world 2-year treatment patterns among patients with psoriatic arthritis treated with injectable biologic therapies.

Curr Med Res Opin 2020 07 23;36(7):1245-1252. Epub 2020 Apr 23.

Janssen Scientific Affairs, LLC, Horsham, PA, USA.

To assess long-term (2-year) biologic treatment patterns of psoriatic arthritis (PsA) patients who initiated adalimumab, certolizumab pegol, etanercept, golimumab, or ustekinumab. Adult patients with ≥1 pharmacy or medical claim for injectable PsA biologics (index date) were identified from the Optum's Clinformatics Data Mart (1 January 2013-31 December 2016). Adherence, persistence, post-discontinuation treatment patterns, and addition of adjunctive medications were evaluated by index biologic. Of 996 patients included (mean [SD] age: 51.5 [12.6] years; female: 49.4%), the most common index biologics initiated were adalimumab (47.9%) and etanercept (34.5%). The mean [SD] proportion of days covered was 0.48 [0.32] for the index biologics. During the 24-month follow-up period, 19.7% of patients persisted on their index biologic; ustekinumab had the highest persistence rate (27.2%), followed by adalimumab (22.0%), golimumab (18.4%), certolizumab pegol (15.6%), and etanercept (15.4%). Of the 800 patients (80.3%) who discontinued their index biologic therapy, 35.0% restarted, 40.1% switched to another biologic, and 31.8% did neither during the follow-up period. The most common biologics patients switched to were adalimumab (31.2%) and ustekinumab (18.7%). Among patients who persisted with their index biologic for ≥90 days ( = 753), ≥1 adjunctive medication was added for 50.1% of patients. The most common adjunctive medications included corticosteroids (28.0% of patients), opioids (17.0%), nonsteroidal anti-inflammatory drugs (NSAIDs) (13.8%), and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) (7.3%). In this real-world study of use of biologic PsA therapies, 24-month persistence was low (19.7%), and treatment was frequently supplemented with adjunctive medications.
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http://dx.doi.org/10.1080/03007995.2020.1754186DOI Listing
July 2020

The Effects of a Video Intervention on Posthospitalization Pulmonary Rehabilitation Uptake. A Randomized Controlled Trial.

Am J Respir Crit Care Med 2020 06;201(12):1517-1524

Harefield Respiratory Research Group and.

Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted. To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake. The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV % predicted, frailty, transport availability, and previous PR experience. The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively ( = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video. A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion.
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http://dx.doi.org/10.1164/rccm.201909-1878OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301747PMC
June 2020

Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W).

Ann Rheum Dis 2020 02 4;79(2):176-185. Epub 2019 Nov 4.

University of California, San Francisco, California, USA.

Objectives: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).

Methods: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.

Results: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.

Conclusion: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.

Trial Registration Number: NCT02696785/NCT02696798.
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http://dx.doi.org/10.1136/annrheumdis-2019-216118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025731PMC
February 2020

Assessing Physical Activity and Sleep in Axial Spondyloarthritis: Measuring the Gap.

Rheumatol Ther 2019 Dec 31;6(4):487-501. Epub 2019 Oct 31.

Swedish Medical Center and University of Washington, Seattle, WA, USA.

Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients' daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA.Funding: Novartis Pharmaceuticals Corporation.Plain Language Summary: Plain language summary available for this article.
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http://dx.doi.org/10.1007/s40744-019-00176-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858410PMC
December 2019

Treatment Patterns with Disease-Modifying Antirheumatic Drugs in U.S. Veterans with Newly Diagnosed Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis.

J Manag Care Spec Pharm 2019 Nov;25(11):1218-1228

Division of Hematology, Department of Internal Medicine, Salt Lake City Veterans Affairs and University of Utah Medical Centers.

Background: Delays in treatment for inflammatory arthritis (IA) are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.

Objective: To characterize treatment initiation patterns in veterans with newly diagnosed rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS).

Methods: ICD-9/10-CM codes and natural language processing were used to identify incident cases of RA, PsA, or AS between January 1, 2007, and December 31, 2015, in patients enrolled in the Veterans Health Administration. Patterns of treatment initiation and nontreatment with disease-modifying antirheumatic drugs (DMARDs) were assessed in the 12-month follow-up period after the incident diagnosis. Outcomes included the percentage of veterans treated with a DMARD, the mean time to the initial DMARD after diagnosis, and the percentage of veterans who accessed rheumatology care before DMARD initiation. To assess outcomes over time, veterans were grouped by year of initial IA diagnosis. Additionally, outcomes were compared between nonbiologic and biologic DMARDs and among IA subtypes (RA, PsA, and AS). Groups were statistically compared with 95% confidence intervals.

Results: The population consisted of 12,118 IA veterans (9,711 RA, 1,472 PsA, and 935 AS), with 91.3% males and a mean age of 63.7 years. The percentage of veterans treated with ≥ 1 DMARD (nonbiologic or biologic) during the 12-month follow-up period increased from 48.8% in 2007 to 66.4% in 2015. In veterans diagnosed with IA in 2015, DMARD treatment was more common for PsA patients (72.9%) and RA patients (68.6%) than for AS patients (28.9%). In the subset treated with a DMARD within 12 months after diagnosis, the mean time to the initial DMARD after diagnosis did not change throughout the observation period (35.5 days for RA, 43.9 days for PsA, and 59.5 days for AS). Rheumatology specialty care was accessed by 87.4% of veterans treated with a nonbiologic DMARD and 92.2% of veterans treated with a biologic DMARD, in patients diagnosed in 2015.

Conclusions: DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in veterans with AS. The time to treatment after diagnosis was stable over time; it was shortest for RA, intermediate for PsA, and longest for AS. DMARD treatment was uncommon in veterans who did not access rheumatology specialty care.

Disclosures: AbbVie Pharmaceuticals and Marriott Daughters Foundation funded this study via investigator-initiated grants. Data analyses were completed by investigators independent of AbbVie and Marriott Daughters Foundation. Walker, Clewell, and Douglas are employed by, and stockholders in, Abbvie. Halwani reports grants from BMS, Kyowa Hakko Kirin, Seattle Genetics, Roche-Genentech, Miragen, Immunedesign, Takeda, Amgen, Pharmacyclics, and Abbvie. The other authors have nothing to disclose.
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http://dx.doi.org/10.18553/jmcp.2019.25.11.1218DOI Listing
November 2019

Measuring Outcomes in Psoriatic Arthritis: Comparing Routine Assessment of Patient Index Data and Psoriatic Arthritis Impact of Disease.

J Rheumatol 2020 10 1;47(10):1496-1505. Epub 2019 Oct 1.

J.A. Walsh, MD, MBA, A. Ogdie, MD, MSCE, Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia;

Objective: To examine the construct validity of Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, poly articular disease, enthesitis, and dactylitis, and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PRO).

Methods: Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014 and 2016. PARC is a longitudinal observational cohort study conducted at 4 US institutions. In this cross-sectional study, construct validity was assessed by examining Spearman correlation coefficients for RAPID3 and PsAID with physician-reported disease activity measures and other PRO [e.g., Medical Outcomes Study Short Form-12 physical component summary/mental component summary (SF-12 PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F)]. Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PsAID12 as outcomes of interest and the hypothesized contextual factors as covariates.

Results: Among 401 patients enrolled in PARC, 347 completed RAPID3 or PsAID12. Of these, most were white females with a mean age of 51.7 years (SD 14.02). RAPID3 and PsAID were highly correlated (r = 0.90). These measures were also correlated with the SF-12 PCS (r = -0.67) and FACIT-F (r = -0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression.

Conclusion: RAPID3 and PsAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PsAID12.
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http://dx.doi.org/10.3899/jrheum.190219DOI Listing
October 2020

Home versus outpatient pulmonary rehabilitation in COPD: a propensity-matched cohort study.

Thorax 2019 10 5;74(10):996-998. Epub 2019 Jul 5.

Harefield Pulmonary Rehabilitation and Muscle Research Laboratory, Royal Brompton and Harefield NHS Foundation Trust, London, UK.

Home-based exercise has been proposed as an equivalent treatment strategy to supervised outpatient pulmonary rehabilitation (PR), but it is not known whether its implementation into clinical practice produces similar benefits to those observed in trials. We compared the real-world responses of 154 patients with COPD undergoing home-based exercise with a matched group attending supervised PR. We observed smaller improvements in exercise capacity with home-based exercise compared with PR, but similar improvements in quality of life. We propose that supervised PR remains the standard of care, with home-based exercise a less effective alternative for those unable to attend PR.
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http://dx.doi.org/10.1136/thoraxjnl-2018-212765DOI Listing
October 2019

Translating Improvements with Ixekizumab in Clinical Trial Outcomes into Clinical Practice: ASAS40, Pain, Fatigue, and Sleep in Ankylosing Spondylitis.

Rheumatol Ther 2019 Sep 28;6(3):435-450. Epub 2019 Jun 28.

NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.

Introduction: Ixekizumab, a humanized interleukin-17A antibody, has shown efficacy in ankylosing spondylitis (AS), with a greater proportion of ixekizumab-treated patients achieving an ASAS40 (Assessment of Spondyloarthritis International Society 40) endpoint compared to placebo. An ASAS40 response is a high standard that is not routinely used in clinical practice. The goals of this study were (a) to measure improvement in ixekizumab-treated patients in the four ASAS treatment response domains and in other patient-reported outcomes, and (b) to determine how the ASAS response was associated with changes in spinal pain at night, fatigue, sleep, and the Short Form 36-Item Physical Component Summary (SF-36 PCS).

Methods: The COAST-V and COAST-W trials were randomized, double-blind, controlled trials examining ixekizumab efficacy in patients with AS who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced, respectively. Data for the ASAS treatment response domains and other outcomes were collected through 16 weeks. Comparisons between treatment groups were made using a mixed-effects model for repeated measures. To determine how the ASAS response was associated with the changes in spinal pain at night, fatigue, sleep, and SF-36 PCS, comparisons were made between patient groups according to their level of treatment response (ASAS40 vs. ASAS20 vs. ASAS20 nonresponse) using analysis of covariance.

Results: Compared with placebo, patients treated with ixekizumab reported significantly greater improvement in the four ASAS treatment response domains and other outcomes (p < 0.05). Results were consistent for bDMARD-naïve and TNFi-experienced patients. Compared to ASAS20 nonresponders, patients who achieved ASAS40 reported significantly greater mean changes in spinal pain at night (1.0 vs. 5.1 for bDMARD-naïve; 0.5 vs. 5.4 for TNFi-experienced), fatigue (0.6 vs. 3.8 for bDMARD-naïve; 0.2 vs. 3.9 for TNFi-experienced), sleep quality (1.1 vs. 4.0 for bDMARD-naïve; 0.8 vs. 4.9 for TNFi-experienced), and SF-36 PCS (2.6 vs. 11.6 for bDMARD-naïve; 1.2 vs. 12.6 for TNFi-experienced) (p < 0.0001).

Conclusion: Patients with AS who were treated with ixekizumab reported greater improvements in multiple patient-reported outcomes than patients who received placebo. Importantly, achieving ASAS40 was associated with a 2.6-fold to 5.3-fold greater improvement in pain, fatigue, sleep, and quality of life for bDMARD-naïve patients, and a 5.1-fold to 18.5-fold greater improvement for TNFi-experienced patients, compared to ASAS20 nonresponders.

Trial Registration: ClinicalTrials.gov identifiers: NCT02696785 and NCT02696798.

Funding: Eli Lilly and Company.
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http://dx.doi.org/10.1007/s40744-019-0165-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702662PMC
September 2019

King's Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference.

Eur Respir J 2019 09 5;54(3). Epub 2019 Sep 5.

Harefield Pulmonary Rehabilitation and Muscle Research Laboratory, Royal Brompton and Harefield NHS Foundation Trust, Harefield, UK.

Health status is increasingly used in clinical practice to quantify symptom burden and as a clinical trial end-point in patients with interstitial lung disease (ILD). The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a brief, validated 15-item, disease-specific, health-related quality of life questionnaire that is increasingly used in clinical trials, but little data exist regarding the minimum clinically important difference (MCID). Using pulmonary rehabilitation as a model, we aimed to determine the responsiveness of KBILD and provide estimates of the MCID.KBILD scores, Chronic Respiratory Questionnaire (CRQ) scores, Medical Research Council (MRC) Dyspnoea score and incremental shuttle walk test (ISWT) distance were measured in 209 patients with ILD (105 with idiopathic pulmonary fibrosis (IPF)) before and after an outpatient pulmonary rehabilitation programme. Changes with intervention and Cohen's effect size were calculated. Anchor-based (linear regression and receiver operating characteristic plots) or distribution-based approaches (0.5 sd and standard error of measurement) were used to estimate the MCID of KBILD domain and total scores.KBILD, CRQ, MRC Dyspnoea and ISWT improved with intervention, and the effect sizes of KBILD domain and total scores ranged from 0.28 to 0.38. Using anchor-based estimates, the MCID estimates for KBILD-Psychological, KBILD-Breathlessness and activities, and KBILD-Total were 5.4, 4.4 and 3.9 points, respectively. Using distribution-based methods, the MCID estimate for KBILD-Chest symptoms was 9.8 points. The MCID estimates for KBILD in IPF patients were similar.In patients with ILD and IPF, KBILD is responsive to intervention with an estimated MCID of 3.9 points for the total score.
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http://dx.doi.org/10.1183/13993003.00281-2019DOI Listing
September 2019

Supplemental oxygen during exercise training in COPD: full of hot air?

Eur Respir J 2019 May 30;53(5). Epub 2019 May 30.

Harefield Respiratory Research Group, Royal Brompton and Harefield NHS Foundation Trust, Uxbridge, UK.

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http://dx.doi.org/10.1183/13993003.00837-2019DOI Listing
May 2019

Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood.

J Autoimmun 2019 08 23;102:126-132. Epub 2019 May 23.

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Division of Rheumatology, Department of Medicine & Lupus Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Background And Objective: Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammation of the sacroiliac joints and the spine that can lead to significant pain, immobility, and disability. The etiology and pathogenesis of ankylosing spondylitis are incompletely understood, though most patients carry the HLA-B*27 allele. The objective of this study was to evaluate DNA methylation changes in ankylosing spondylitis with the goal of revealing novel mechanistic insights into this disease.

Methods: Genome-wide DNA methylation analysis was performed in whole blood DNA samples using the Infinium MethylationEPIC array in patients with ankylosing spondylitis compared to age, sex, and race matched patients with osteoarthritis as a non-inflammatory disease control. We studied 24 patients with ankylosing spondylitis, including 12 patients who carry HLA-B*27 and 12 patients who are HLA-B*27 negative. DNA methylation analysis was performed with adjustment for blood cell composition in each sample.

Results: We identified a total of 67 differentially methylated sites between ankylosing spondylitis patients and osteoarthritis controls. Hypermethylated genes found included GTPase-related genes, while hypomethylated genes included HCP5, which encodes a lncRNA within the MHC region, previously associated with genetic risk for psoriasis and toxic epidermal necrolysis. Carrying HLA-B*27 was associated with robust hypomethylation of HCP5, tubulin folding cofactor A (TBCA) and phospholipase D Family Member 6 (PLD6) in ankylosing spondylitis patients. Hypomethylation within HCP5 involves a CpG site that contains a single nucleotide polymorphism in linkage disequilibrium with HLA-B*27 and that controls DNA methylation at this locus in an allele-specific manner.

Conclusions: A genome-wide DNA methylation analysis in ankylosing spondylitis identified DNA methylation patterns that could provide potential novel insights into this disease. Our findings suggest that HLA-B*27 might play a role in ankylosing spondylitis in part through inducing epigenetic dysregulation.
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http://dx.doi.org/10.1016/j.jaut.2019.04.022DOI Listing
August 2019
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