Publications by authors named "Pedro M Machado"

Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

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Objectives: To evaluate the impact of using Simplified Disease Activity Index (SDAI)-LDA (low disease activity) versus different definitions of remission as a treatment target in established rheumatoid arthritis.

Methods: A meta-epidemiological study of individual patient data from eight randomised controlled trials was performed. Four definitions of the target were considered at 6 months: (1) SDAI-LDA: SDAI≤11; (2) SDAI-Remission: SDAI≤3.

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Inclusion body myositis (IBM) remains an enigmatic and complex muscle disorder where a deeper understanding of disease pathomechanisms and the identification of potential genetic contributors represent an unmet need. The absence of effective treatments has spurred endeavours to reassess the interplay between degeneration, including autophagy, mitochondrial dysfunction and proteasomal dysregulation, and autoimmunity. IBM is unique among the other idiopathic inflammatory myopathies owing to its molecular signature involving highly differentiated cytotoxic T cells that evade immune regulation.

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Objectives: This study aims to establish expert consensus recommendations for clinical information on imaging requests in suspected/known axial spondyloarthritis (axSpA), focusing on enhancing diagnostic clarity and patient care through guidelines.

Materials And Methods: A specialised task force was formed, comprising 7 radiologists, 11 rheumatologists from the Assessment of Spondyloarthritis International Society (ASAS) and a patient representative. Using the Delphi method, two rounds of surveys were conducted among ASAS members.

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Background: A consensus definition for active sacroiliitis by MRI, mentioned in the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), was published in 2009 and included a qualitative and quantitative MRI cut-off component. In 2021, updates to the quantitative component were preliminarily proposed. This post hoc analysis of part A of the phase 3 open-label C-OPTIMISE study (NCT02505542) explores the differences by applying the 2009 and preliminary 2021 inflammatory cut-offs on clinical outcomes of axSpA patients treated with certolizumab pegol.

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Objectives: Timely diagnosis remains a challenge in axial SpA (axSpA). In addition, data are scarce on the impact of diagnostic delay and disease progression in affected individuals. The British Axial Spondyloarthritis Inception Cohort (BAxSIC) study aims to investigate the impact of newly diagnosed axSpA, the natural history of the disease and the effect of diagnostic delay on disease outcomes.

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Article Synopsis
  • Genome-wide association studies (GWASs) are effective in linking genetic variants to various human traits and diseases, but they often require large sample sizes, making it tough to study rarer diseases like myositis, which severely affect patients' quality of life.
  • The researchers used a feature engineering method to leverage data from larger IMD GWASs, discovering 17 immune-mediated diseases genetically related to myositis, including conditions like systemic sclerosis and Sjögren's syndrome.
  • They identified seven potential new genetic links to myositis, hinting that immune system genes may play a role in the disease, and suggest this method could enhance genetic research in other rare conditions as well.
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  • * The review aims to gather and assess existing MRI scoring systems to create an evidence-based foundation for a universal standardized system that can be used in both research and clinical settings.
  • * A systematic search of electronic databases will be conducted to consolidate information on MRI scanning protocols for evaluating muscle involvement in IIMs, with the goal of producing guidelines for consistent clinical and research practices.
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  • The study assessed the effectiveness of the Inclusion Body Myositis Functional Rating Scale (IBMFRS) in measuring physical function in patients with IBM, focusing on its validity, reliability, responsiveness, and meaningful change threshold.
  • Data were collected from a 20-month multi-center clinical trial, employing various statistical methods to test the scale’s performance, revealing strong correlations with other health outcomes and reliability in its administration formats.
  • Results indicated that IBMFRS is a dependable tool for evaluating the impact of IBM on patients, with a score drop of 2 points considered a significant decline in function.
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Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis.

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Objectives: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).

Methods: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.

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Introduction: Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however, there is limited guidance for clinicians to follow regarding the most appropriate management options. The objective of this scoping review is to understand and map the extent of evidence in relation to the factors that relate to the outcome of non-pharmacological interventions on MSK condition-related fatigue across the lifespan.

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Article Synopsis
  • The phase IIIb SURPASS study aimed to compare spinal radiographic progression in patients with radiographic axial spondyloarthritis who were treated with secukinumab (an interleukin-17A inhibitor) versus adalimumab biosimilar (a tumor necrosis factor inhibitor).
  • The study involved 859 biologic-naive patients at high risk for progression, assessing outcomes like the proportion with no progression after 104 weeks and the safety of the treatments.
  • Results showed no significant difference in radiographic progression between secukinumab and adalimumab biosimilar, with overall low progression rates observed in all treatment groups and no unexpected safety issues reported.
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Objective: To assess which definition of remission best predicts good radiographic outcome (GRO) and good functional outcome (GFO) in rheumatoid arthritis, focusing the updated American College of Rheumatology/European Alliance of Associations for Rheumatology criteria.

Material And Methods: Meta-analyses of individual patient data (IPD) from randomised controlled trials (RCTs). Six definitions of remission were considered: (1) Boolean with Patient Global Assessment (PGA)≤1 (Boolean); (2) Simplified Disease Activity Index (SDAI)≤3.

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Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace.

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Article Synopsis
  • Sporadic inclusion body myositis (IBM) primarily affects individuals over 40 and leads to progressive muscle weakness, with no effective treatments available, particularly for associated swallowing difficulties.
  • Up to 80% of IBM patients experience dysphagia, increasing their risk of severe complications like aspiration pneumonia, although the exact causes of this impairment remain unclear.
  • Current assessment methods for dysphagia in IBM, such as video fluoroscopic swallowing studies (VFSS), are limited by radiation exposure and a lack of validated tools, prompting a need for further development of alternative imaging techniques and approaches for evaluating swallowing difficulties.
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Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle injury. Until recently, there was little insight into the pathogenesis of idiopathic inflammatory myopathies, which challenged the recognition of the breadth of heterogeneity of this group of diseases as well as the development of new therapeutics. However, the landscape of idiopathic inflammatory myopathies is evolving.

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Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs.

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Article Synopsis
  • The objective of the study was to evaluate the effectiveness and safety of drug interventions for reducing fatigue in individuals with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) to guide recommendations from the European Alliance of Associations for Rheumatology.
  • A systematic review analyzed data from various medical databases, resulting in 19 randomized controlled trials (RCTs) that met the criteria for inclusion, focusing on different drug treatments.
  • Key findings revealed that several drugs, including Adalimumab and Golimumab, significantly reduced fatigue in rheumatoid arthritis, with promising results from other medications in related conditions, indicating both efficacy and safety.
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Objectives: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs.

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