Dafna D Gladman

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Verified

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• MD, FRCPC
• Senior Researcher at University of Toronto

Objectives Lupus nephritis (LN) is associated with significant renal morbidity, although some patients may experience a responsive and monophasic course. We aimed to assess the proportion of LN patients with such a course and identify its associated baseline characteristics. Methods This retrospective study included SLE patients from an observatio...

Objective We aimed to assess whether high‐sensitivity C‐reactive protein (hsCRP) levels could predict the development of psoriatic arthritis (PsA) in patients with psoriasis. Methods We analyzed data from a prospective cohort of patients with psoriasis without PsA at enrollment. Participants were assessed annually by a rheumatologist for signs and...

Objective Metabolic syndrome (MetS) is a known comorbidity of psoriatic arthritis (PsA) and is associated with PsA disease activity. We aimed to explore the association between MetS and radiographic features (peripheral and axial) in PsA. Methods We included patients with PsA followed at our prospective observational cohort for the period between...

Background Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease with a greater surface area of skin involvement, co-morbidity burden and impact on quality of life. Prognostic biomarkers of psoriasis severity could improve allocation of clinical resources and enable earlier int...

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptib...

Objectives Genetics significantly impact systemic lupus erythematosus (SLE) risk, disease manifestations, and damage. Our aim was to identify genetic risk loci for disease activity burden over time. Methods We included participants from a tertiary care Lupus Clinic. Participants met ACR and/or SLICC classification criteria for SLE, were genotyped...

Objective We aimed to explore the prevalence of degenerative disc disease (DDD) in psoriatic arthritis (PsA) patients younger than 50 and describe the factors associated with its development. We also examined the association between radiographic axial imaging findings and inflammatory back pain (IBP) and mechanical back pain (MBP). Methods We incl...

Background Kidney function is not routinely assessed during pregnancy. Several studies have proposed antepartum kidney function, particularly 2 nd trimester kidney function, as a potential predictor of adverse pregnancy outcomes. It has been previously established that patients with Systemic Lupus Erythematosus are at increased risk for adverse pre...

Objective To identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq). Method Peripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, three patients with PsC and two HC were profil...

Objective To assess the longer-term impact of bimekizumab to 1 year on patient-reported symptoms, health-related quality of life (HRQoL), and work productivity in patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR) up to 1...

Objective To assess long-term tofacitinib efficacy and safety in patients with PsA with or without prior biologic (b)DMARD exposure. Methods Data were pooled post hoc from three Phase (P)3 and one long-term extension (LTE) PsA studies and stratified by TNF inhibitor-inadequate responder (TNFi-IR) or bDMARD-naïve patient status at P3 study baseline...

Objectives The primary objective of this study was to assess the impact of extramusculoskeletal manifestations (EMMs) and peripheral musculoskeletal features on first biologic drug survival in subjects with axial spondyloarthritis (axSpA). The secondary objective was to evaluate the impact of reasons for treatment discontinuation. Methods A total...

Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease with various joint and skin manifestations and multiple associated comorbidities. The management of PsA is important not only in controlling disease activity and preventing subsequent damage but also in improving the quality of life and reducing mortality. Over the years, numerous dr...

Background Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study...

Objective To determine if serum interferon (IFN)-α levels at the time of a lupus nephritis (LN) flare are associated with renal outcomes. Methods Patients with an LN flare who had a preflare estimated glomerular filtration rate (eGFR) ≥60 mL/min were included in the study. The following outcomes were ascertained: (1) Time to first and second LN fl...

Psoriatic arthritis is an inflammatory arthritis that affects around 30% of patients with psoriasis. The disease spectrum includes peripheral arthritis, enthesitis, tenosynovitis, dactylitis, axial involvement, and skin and nail psoriasis in most patients. In addition to the cutaneous and musculoskeletal manifestations, several comorbidities can co...

Objectives Chronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify risk factors for CKD development. Methods We included patients with PsA followed by our prospective observational cohort. We defined CKD as an est...

Objectives Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes. Methods We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate...

Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. Pooled data from phas...

Objectives To assess impact of bimekizumab treatment on patient-reported outcomes and health-related quality of life (HRQoL) in patients with active psoriatic arthritis (PsA), using 16-week data from two phase 3 studies. Methods BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug (bDMARD)-naïve) and BE COMPLETE (NCT03896581; tum...

Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). Post hoc analyses evaluated 1120 patients with PsA rec...

Objective To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. Methods We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), metho...

Objectives Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA. Methods FOREMOST (NCT03747939) was a phase 4 multicentre, randomised, double-blind, placebo-controlled trial. Patients had early (symptom duration ≤5 years) oligoarticular PsA (>1 b...

Objectives Membranous lupus nephritis (MLN) is thought to have a more benign course than proliferative lupus nephritis (PLN). We aimed to determine the differences in short and long-term outcomes between patients with MLN and PLN. Methods We included patients with first biopsy-proven MLN and PLN. Short-term outcomes included complete proteinuria r...

Introduction: There are several treatment controversies that have emerged in spondyloarthritis and psoriatic arthritis. These are related to the nature of the conditions as well as to the use of medications. Areas covered: This review, which included a search of PubMed database as well as the references within the articles provides an overview o...

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)–Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group provided updates at the GRAPPA 2023 annual meeting on its work to evaluate composite outcome measures for PsA. An ongoing systematic literature review is in progress to evaluate psych...

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) started in August 2003 with 40 initial participants and celebrated its 20th anniversary with 1036 members, many of whom attended the annual meeting in Dublin, Ireland, on July 15 to 17, 2023. GRAPPA arose from a need experienced by psoriatic arthritis (PsA) and psor...

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN)/research committee met during the GRAPPA 2023 annual meeting. Updates were provided on GRAPPA research projects, including the Axial Involvement in Psoriatic Arthritis (AXIS), Axial Psoriatic Arthritis Molecular and Clinical Char...

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Character...

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting was held on July 13 to 15, 2023, in Dublin, Ireland, and was attended by 285 rheumatologists, dermatologists, trainees, patient research partners (PRPs), representatives of patient organizations, and industry partners. The 20th anniversary of GRA...

Objective Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. Methods The phase 2 trial (ClinicalTrials.gov identifier: NCT0388105...

Objective To provide a set of living treatment recommendations that will provide contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada. Methods The Spondyloarthritis Research Consortium of Canada (SPARCC), in conjunction with the Canadian Rheumatology Association, organized a treatment recommendations p...

Background Lupus nephritis (LN) occurs in approximately 50% of patients with systemic lupus erythematosus (SLE). Class V, membranous LN (MLN), is thought to have a more benign course than proliferative disease. Objectives We aimed to determine the differences in short and long-term outcomes between patients with MLN and Proliferative LN (PLN). Me...

Background Patients (pts) with psoriatic arthritis (PsA) can potentially develop axial inflammation in the sacroiliac joints (SIJs) and/or spine. Although validated classification criteria exist for axial spondyloarthritis, established criteria for classifying axial PsA are lacking. STAR (NCT04929210), a Phase 4, multicenter, randomized, controlled...

Background Oligoarticular psoriatic arthritis (PsA, ≤4 joints affected), although common, is understudied, as most clinical trials require patients (pts) to have ≥3 swollen and tender joints. The FOREMOST study (NCT03747939) is the first large, phase 4, multicenter, randomized, placebo (PBO)-controlled trial to demonstrate efficacy of apremilast (A...

Background Most clinical trials of PsA exclude patients (pts) with early oligoarticular (oligo) disease and there is limited evidence to drive treatment decisions in this setting. Objectives We report 48-week (wk) efficacy and safety of apremilast (APR) vs placebo (PBO) in pts with early oligo PsA. Methods FOREMOST (NCT03747939), a multicenter, r...

Background Dietary Interventions in psoriatic arthritis (DIPSA) is a randomized controlled trial (RCT) assessing the efficacy of dietary modifications in patients with psoriatic arthritis (PsA). Ideally, the design of an adjunct therapy trial and the intervention itself should engage patients in a positive experience. Objectives To describe patien...

Background Fatigue is commonly reported by patients (pts) with psoriatic arthritis (PsA) and contributes to disease burden. The fully human interleukin (IL)-23p19-subunit inhibitor guselkumab (GUS) induces clinically meaningful and sustained fatigue improvements through 1 year (y), with GUS exhibiting a substantial direct effect on fatigue, indepen...

Background The incidence of degenerative disc disease (DDD) increases with age, but it may also occur in younger adults. No previous large-scale study investigated the prevalence and clinical significance of DDD in psoriatic arthritis (PsA). Objectives We aimed to define the prevalence of DDD in patients with PsA younger than 50 and describe the f...

Background Late-onset psoriatic arthritis (PsA) may be associated with elevated acute phase reactants, higher joint count, and erosive disease at diagnosis.[1,2] Given potential phenotype differences and increasing prevalence with aging populations, it is important to establish the efficacy of current treatments in late-onset PsA. Previous analyses...

Background Tuft resorption (TR) is an important radiographic feature of psoriatic arthritis (PsA). No previous large-scale study has investigated the prevalence and clinical significance of TR in PsA. Objectives We aimed to define the prevalence of TR in patients with PsA, the clinical and radiographic features associated with it, and the predicto...

Background Simple and accessible biomarkers that predict the development of psoriatic arthritis (PsA) among psoriasis patients are critically needed to improve early detection of high-risk individuals. High-sensitivity C-Reactive Protein (hs-CRP) is a biomarker of systemic inflammation. Objectives We aimed to assess whether higher levels of hs-CRP...

Background Chronic kidney disease (CKD) is a recognized comorbidity of psoriatic arthritis (PsA). Long-term renal outcomes and CKD risk factors in PsA have not been adequately studied. Objectives We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes, and identify risk factors for CKD development. M...

Objectives To evaluate 1-year bimekizumab efficacy in PsA from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. Methods BE OPTIMAL (NCT03895203; biologic DMARD [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to TNF inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extens...

Objectives This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. Methods Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity sta...

Background Elevated levels of interferons (IFN) are a hallmark of Systemic Lupus Erythematosus (SLE) and have been linked to disease flares, but the precise mechanisms by which this occurs remain unclear. To address this question, we examined the association between IFN-induced proteins (IIPs) and the immune changes in flaring and quiescent SLE pat...

In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of saf...

Objective In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Methods Patients with active PsA in DISCOVER-1 and DISCOVER-2 (Clinica...

Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. Met...

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST – a Phase 4 Randomized Controlled Trial Laure Gossec1, Dafna Gladman2, Laura C. Coates3, Jacob Aelion4, Jitendra Vasandani5, Jyotsna Reddy6, Rebecca Wang6, Michele Brunori6, Stephen Colgan6, Philip Mease7 1Sorbonne Université and Pitié Salp...

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic d...

The APPRAISE study was conducted to better understand the 12-month effectiveness, tolerability, and patient satisfaction with apremilast treatment for patients with psoriatic arthritis (PsA) in real-world settings. APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per rout...

Objective The aim of this study was to determine the immunologic profile associated with disease flares in patients with systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following a flare. Methods Multiparameter flow cytometry was used to examine 47 immune popul...

To evaluate the effect of guselkumab on work productivity and nonwork daily activity impairment and general health status through 2 years in patients who were biologic-naïve with active psoriatic arthritis (PsA) in the phase 3 DISCOVER-2 clinical trial. Adult patients with PsA were randomized to subcutaneous injections of guselkumab 100 mg every 4...

Objective Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA. Methods This was a multi-region,...

Objectives To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors. Methods Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VIT...

Objectives To investigate psychometric performance of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) total and individual item scores in patients with psoriatic arthritis (PsA) and to estimate score change thresholds and scores corresponding to different levels of symptom/impact severity. Methods Data up to week 16 from 1252 patients...

Objective Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte...

Objectives To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of interleukin-17F in addition to IL-17A, vs other biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for psoriatic arthritis (PsA) using network meta-analysis (NMA). Methods A systematic literature review (most recent up...

Objective To determine if the serum levels of neutrophil extracellular trap (NET) remnants (Elastase-DNA and HMGB1-DNA complexes) at the time of a lupus nephritis (LN) flare predict renal outcomes in the following 24 months. Methods This was a retrospective study performed in prospectively followed cohorts. The study included two cohorts: an explo...

Objective The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Ince...

Objective Psoriatic arthritis (PsA) is an immune‐mediated inflammatory arthritis, associated with psoriasis, that significantly increases morbidity and mortality risk. We currently lack the means of predicting which patients with psoriasis will develop PsA, and a large number of patients remain undiagnosed. Regulation of gene expression through DNA...

Objectives The goal of this study was to identify protein and transcriptional biomarkers and pathways associated with baseline disease state, the effect of filgotinib (FIL) treatment on these biomarkers, and to investigate the mechanism of action of FIL on clinical improvement in patients with active psoriatic arthritis (PsA). Methods The phase II...

Objectives To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. Methods An international Task Force formed the questions for the systematic literature reviews (January 2018–December 2022), followed by formulation and finalisation of the statements after a series of meetings. A...

Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER...

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis su...

Objectives: To investigate the incidence of demyelinating disease (DD) among spondyloarthritis (SpA) patients and identify risk factors that predict DD in this patient population. Methods: Axial SpA (axSpA) and psoriatic arthritis (PsA) patients were identified from a longitudinal cohort database. Each group was analysed according to the presence...

Objective: To address sub-optimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a 5-year disease-specific cardiovascular risk prediction model. Methods: We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardi...

Objective To estimate the prevalence of COVID-19 infection among patients with psoriatic arthritis (PsA), understand patients' perspectives regarding their risk of COVID-19 infection, and evaluate the standard of virtual care offered during the early phases of the pandemic. Methods An online survey was conducted between June and September 2021 in...

Background Psoriatic arthritis (PsA) is a chronic inflammatory condition predominantly affecting the peripheral joints. However, some patients with PsA can experience axial involvement which is manifested with back pain and associated with increased burden of illness. Objectives The aim of this post hoc analysis was to determine the efficacy of ix...

Objective: A simple, scalable tool that identifies psoriasis patients at high risk for developing psoriatic arthritis (PsA) could improve early diagnosis. We aimed to develop a risk prediction model for the development of PsA and to assess its performance among patients with psoriasis. Methods: We analyzed data from a prospective cohort of psori...

Background Hydroxychloroquine is one of the major treatment of SLE, but its effectiveness is impaired by non-adherence, reported to range from 3% to 85% in SLE patients. Our objective was to assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years o...

Background Mesangial lupus nephritis is considered benign with minimal potential for developing advanced chronic kidney disease (CKD). However, some patients still develop advanced CKD and end-stage renal disease (ESRD). Our objective was to describe the factors associated with the development of CKD stage IV or worse in patients with LN II. Metho...

Background Many SLE patients develop lupus nephritis (LN) and receive mycophenolate mofetil (MMF), a teratogenic drug. Guidelines recommend azathioprine (AZA) in SLE pregnancy without providing guidance on pharmacogenetic testing and therapeutic monitoring although these may help personalize therapy (e.g., identifying ‘shunters’, non-adherence). We...

Background Lupus nephritis (LN) leads to end stage kidney disease (ESKD) in 17–33% after 10 years. The prevalence of chronic kidney disease stage IV (eGFR=15–29ml/min/1.73m2) is not known. Our objective was to determine the impact of time to remission and number of flares on the development of advanced CKD in LN. Methods Patients with LN were retr...

Background Time to complete remission, subsequent flares and time on immunosuppressives after remission are major determinants of the progression to advanced chronic kidney disease (CKD) in lupus nephritis (LN). However, the impact of these factors on the rate of glomerular filtration rate (GFR) deterioration is not known. Our objective was to dete...

Background Early complete remission (within 12 months) is considered an important protective factor against development of chronic kidney disease (CKD) in lupus nephritis (LN). However, a certain proportion of such patients still develop advanced CKD. Our objective was to describe the factors associated with the development of CKD stage IV or worse...