Robert John Moots

• MD, PhD
• University of Liverpool

Reply to ‘Enhance the transparency in the development of the BAD living guidelines’ by Liu et al.

Objective The objective of this study was to report 52‐week safety and efficacy of ianalumab from phase 2b dose‐finding study in patients with Sjögren's disease (SjD). Methods Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300...

Objectives Whilst biologic therapy is used for Behçet’s Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence—and no predictive biomarkers to optimally inform choice. BIO-BEHÇET’S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologic...

Background While biologic therapy, typically with infliximab or Roferon, was used for Behçet syndrome after first-line immunosuppressants, no high-quality randomised trials or predictive biomarkers were available. Objective To undertake a randomised controlled clinical trial of infliximab versus Roferon in Behçet syndrome and identify potential bi...

Produced in 2024 by the British Association of Dermato logists NICE has renewed accreditation of the process used by the British Association of Dermatologists to produce clinical guidelines. The renewed accreditation is valid until 31 May 2026 and applies to guidance produced using the processes described in the updated guidance for writing a Briti...

Background: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. Objective: To assess symptomatic benefits of methotrexate in knee OA (KOA). Design: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June...

Background Behçet’s syndrome (BS) is a rare multi-systemic vasculitis of unknown aetiology. Fibromyalgia syndrome (FMS) is more prevalent in rheumatological conditions such-as BS, than the general population. However, there is limited research into the aetiology and characteristics of pain in BS. Objectives To describe the pain characteristics and...

Objective Identifying that dysfunction of the IL-23/17 axis underlies psoriatic arthritis (PsA) has led to the development of effective targeted therapies, such as the IL-17A inhibitor, secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function i...

Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However, clinical trials...

Background Behçet’s syndrome (BS) is a rare multi-organ systemic vasculitis of unknown aetiology with hallmark manifestations of mucocutaneous ulcers and skin lesions. Morbidity is high in BS; with high prevalence of pain, fatigue and poor quality of life. Fibromyalgia syndrome (FMS), a common cause of widespread musculoskeletal (MSK) pain, is more...

Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials...

Background We are continually learning how to best manage patients testing positive for SARS-CoV-2 [coronavirus disease 2019 (COVID-19)]. This is particularly challenging in rare autoimmune conditions, where immune system dysfunction, whether by disease or treatment, has the potential to impact on the course of COVID-19 in several ways. Case Prese...

Background Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safet...

Introduction Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations. Methods Demographic, clinical, and laboratory features of...

Behçet’s disease (BD) is a multisystem inflammatory disorder of unknown etiology, characterized by oral and genital ulceration, with other complications including eye, skin, joint, and central nervous system (CNS) lesions. Diagnosis is based on clinical findings, which may differ between patients. There is a strong genetic basis for BD; however, on...

Neutrophil-derived microvesicles (NDMVs) have the potential to exert anti-inflammatory effects. Our study aimed to explore the effects of NDMVs on proinflammatory cytokines expressed by tumor necrosis factor α (TNFα)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing su...

Background Sjogren’s syndrome (SS) is an autoimmune disease affecting excretory glands and characterised by B-cell hyperactivity. Ianalumab (VAY736) is a human monoclonal antibody to B-cell activating factor receptor, engineered for direct ADCC-mediated B-cell depletion. A Phase 2b study evaluated the dose-response of VAY736 vs placebo (PBO) in EUL...

Background Few data exist on the association between increased BMI and response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). We aimed to explore the association between increased (overweight or obese) BMI on csDMARD-prescribing, methotrexate-dose and disease activity over 12-months. Met...

Background/Aims Neutrophils contribute to disease pathology in inflammatory diseases including rheumatoid arthritis (RA). Activated RA neutrophils release ROS and proteases which damage joints, and produce neutrophil extracellular traps (NETs) that expose citrullinated nuclear proteins leading to the development of ACPA auto-antibodies. We previou...

Objectives Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA. Methods Biologic naïve participants from a national axSpA register completed the Hosp...

Objectives This study aimed to test the performance of the “new” American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, that include anti-nuclear antibodies (ANA) positivity as entry criterion, in juvenile-onset systemic lupus erythematosus (jSLE). Methods Performance of the ACR/EULAR-2019 criteria were com...

Objectives: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). Methods: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society...

Background Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells—the target for rituximab—in the main disease tiss...

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms,...

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analyzed paired blood and S...

Objective Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and: 1) change in disease indices over time; 2) binary response definitions; 3) time-to-treatment-discontinuation....

Introduction Le syndrome de Sjögren primaire (SSp) est une maladie auto-immune multi-organe touchant principalement les glandes exocrines et caractérisée par une hyperactivité des lymphocytes B (LB). Aucun traitement systémique approuvé n’est disponible. Le ianalumab (VAY736) est un anticorps monoclonal IgG1 entièrement humanisé anti- BAFF récepteu...

Primary systemic vasculitides (PSV) are multisystem diseases associated with high morbidity and mortality, particularly if not treated in a timely manner. In recent decades, clinical trials have delivered considerable evidence to underpin optimal diagnostic and therapeutic approaches. This article provides a brief overview of PSV in adults, focusin...

Objective Whether comorbidities influence disease activity assessment in axial SpA (axSpA) is unclear. Comorbidities inflate DAS28 in rheumatoid arthritis through the patient global score. We examined whether axSpA disease activity measures are differentially affected, and whether comorbidities inflate the AS disease activity score (ASDAS) through...

Objectives. Comorbidities are common in people with axial spondyloarthritis (axSpA). In this systematic review and meta-analysis, we aimed to: (i) describe the prevalence of commonly reported comorbidities, (ii) compare comorbidities between axSpA and control populations, and (iii) examine the impact of comorbidity burden on axSpA outcomes. Method...

Neutrophils are key players in the pathophysiological process underlying inflammatory conditions not only by release of tissue-damaging cytotoxic enzymes, reactive oxygen species (ROS) but also by secretion of important immunomodulatory chemokines and cytokines. Here, we report the effects of the novel agent APPA, undergoing formal clinical develop...

Interferons (IFNs) are key regulators of a number of inflammatory conditions in which neutrophils play an important role in pathology, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), where Type I IFNs are implicated in disease pathology. However, IFNs are usually generated in vivo together with other cytokines that also ha...

Introduction: Tumour necrosis factor inhibitors (TNFi), have revolutionised the treatment of rheumatic diseases. Whilst extremely efficacious, the original TNFi also carried a high acquisition cost that limited their use. “Biosimilar” TNFi’s, developed on expiry of the patents for the biooriginators, have comparable efficacy and safety, are less ex...

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and S...

Interferons (IFNs) are key regulators of a number of inflammatory conditions in which neutrophils play an important role in pathology, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), where Type I IFNs are implicated in disease pathology. However, IFNs are usually generated in vivo together with other cytokines that also ha...

Background: Rheumatoid arthritis (RA) is associated with increased body mass index (BMI)- 60% of patients are either overweight or obese. Obesity in RA has been shown to predict reduced response to biologic therapy including tumour-necrosis-factor inhibitors (TNFi) [1]. However, it is not clear whether increased BMI influences response to all TNFi...

Background Comorbidities are common among patients with axial spondyloarthritis (axSpA). The majority of axSpA patients have at least one comorbid medical condition in addition to any extra-articular manifestations [1]. Comorbidity ‘burden’ is associate with poorer function, quality of life and work-related outcomes [2]. They also influence treatme...

Background Biologic therapies have revolutionised therapy in inflammatory diseases such as psoriatic arthritis (PsA), driving major improvements in outcomes. Th17 cells appear to play a key role in the pathogenesis of PsA, and IL-17 can trigger the release of chemoattractants such as CXCL8 and CCL20, leading to the further infiltration of other imm...

Background Primary Sjogren’s syndrome (pSS) is a multi-organ autoimmune disease mainly affecting excretory glands and characterised by B-cell hyperactivity. No approved systemic treatment is available. Ianalumab (VAY736) is an anti-B-cell activating factor (BAFF) receptor fully human monoclonal antibody, engineered for direct ADCC-mediated B-cell d...

Background Worldwide, >60% patients with rheumatoid arthritis (RA) are overweight/obese (body mass index, BMI≥25kg/m2). Studies demonstrate poorer disease outcomes and health-related quality of life in these patients. However, little is known about the effect of increased BMI on drug choice, dosing, or treatment response. Objective: To explore the...

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 1% of the Caucasian population worldwide causing significant morbidity. The genetics of disease pathogenesis remains poorly understood despite recent advances in high throughput genotyping and sequencing. Biological agents (e.g. TNF inhibitors, TNFi) have s...

Background POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) is a rare, disabling, auto-inflammatory condition that may present to multiple specialties including rheumatology. We describe a case fulfilling all diagnostic criteria. Methods Please refer to the results section. Results A 52 year old lady of Ve...

Background Biologic therapies have transformed the outlook for RA but the significant health economic impact of these therapies has highlighted the need to define predictive markers of response. Rituximab (RTX) is licensed for use following failure of csDMARDs and TNF inhibitor (TNFi) therapy. However, in this increasing therapeutically resistant c...

Background Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals...

Objective Observational data facilitate examination of treatment‐effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). Methods We used lo...

Background Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rar...

BACKGROUND Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rar...

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease with symptoms including dryness, fatigue, and pain. The previous work by our group has suggested that certain proinflammatory cytokines are inversely related to patient-reported levels of fatigue. To date, these findings have not been validated. This study aims to validate t...

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response.

Objective To provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR). Methods ORAL Strategy ( NCT02187055 ), a phase IIIB/...

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster ana...

Background: Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. / Methods: We did hierarchical cluster...

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren’s syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster...

Background: The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA). Methods: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients f...

Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors o...

Background There is a pressing need to understand more about the psychological experience in patients with Behçet’s Disease (BD). The presence of poor wellbeing, low mood and anxiety may affect the ability to both manage and cope with this complex disorder and also impact upon the perception and experience of disease activity1,2,3. Objectives Our...

Background Behçet’s Disease(BD) is a rare chronic autoinflammatory condition that can lead to irreversible organ damage. The potential for multi-organ involvement and fluctuating activity highlights the need to perform a careful and systematic assessment of disease activity that is sensitive to change. Several disease activity tools have been used...

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. Greater improvements in efficacy outcomes have been reported with tofacitinib 5 mg BID ± csDMARDs in patients (pts) with early vs established RA.¹,² Objectives This post hoc analysis of ORAL Strategy data evaluated the efficacy and safety of tofacitinib monotherapy, tofacitin...

Objectives: This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States. Methods: We performed a cross-sectional study using electronic medical records from two academic hospitals in th...

Objectives. To compare comorbidities and biologic DMARD (bDMARD) use between ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States (US). Methods. We performed a cross-sectional study using electronic medical records from two...

Objectives: To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. Methods: We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of...

Objectives To report on fatigue in patients from the United Kingdom Primary Sjögren’s Syndrome Registry identifying factors associated with fatigue and robust to assignable causes such as comorbidities and medications associated with drowsiness. Methods From our cohort (n=608) we identified those with comorbidities associated with fatigue, and tho...

Background Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients...

Neutrophil Extracellular Traps (NETs) are implicated in the development of auto-immunity in diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) through the externalization of intracellular neoepitopes e.g., dsDNA and nuclear proteins in SLE and citrullinated peptides in RA. The aim of this work was to use quantitative...