Initiation of vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A prospective 24-week study with imaging assessments.

BACKGROUND: A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested. AIMS: We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI). METHODS: A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn's disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24 weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24 weeks. RESULTS: Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2 years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48 years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response. CONCLUSION: Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24 weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.

Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Living Treatment Recommendations for the Management of Axial Spondyloarthritis.

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 panel composed of rheumatologists, researchers, allied health professionals, and a patient advocate. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach was used in which existing guidelines were adopted or adapted to a Canadian context. Recommendations were also placed in a health equity framework. RESULTS: 56 recommendations were made for patients with active axSpA, stable axSpA, active or stable axSpA, comorbidities, and for assessment, screening, and imaging. Recommendations were also made for principles of management, disease monitoring, and ethical considerations. CONCLUSION: These living treatment recommendations will provide up to date guidance for the management of axSpA for Canadian practice. As part of the living model, they will be updated regularly as changes occur in the treatment landscape.

Residual Disease Activity in Canadian Patients With Psoriatic Arthritis Treated With Advanced Therapies: Results From a Multiregistry Analysis (UNISON-PsA).

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 multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies. RESULTS: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East. CONCLUSION: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment.

The incidence and risk factors for venous thromboembolic events in patients with psoriasis and psoriatic arthritis.

OBJECTIVES: The risk of arterial vascular events is increased in patients with psoriatic disease (PsD), however, limited information exists about the risk of venous thromboembolism (VTE) in these patients. We assessed the incidence and risk factors for VTE in patients with PsD. METHODS: A multicentre cohort study was conducted involving patients with PsD followed prospectively from 1994 to 2020. Information about VTE, including pulmonary embolism (PE) and deep venous thrombosis (DVT), was obtained from provincial hospitalization databases. The incidence rate and cumulative probability of developing VTE were computed. Cox proportional hazards models were used to assess the association between risk factors, including comorbidities and disease-related factors, and the first VTE. RESULTS: A total 2,433 patients with PsD were analysed with 26 incident VTE (7 DVT alone, 12 PE alone, and 7 both PE and DVT). The incidence rates of the first VTE, DVT, and PE were 12, 6.5, and 8.8 events per 10,000 patient-years, respectively. The cumulative proportion of individuals developing VTE was 4.6% by 80 years of age. Independent predictors for VTE included older age, diabetes mellitus, and corticosteroid usage (all p<0.05). CONCLUSION: Older patients with PsD, those with diabetes, and those using corticosteroids are at a higher risk of developing VTE. Risk stratification of patients with these identified risk factors for VTE will allow for more individualized patient management and improved medication selection.

Pro- and anti-inflammatory eicosanoids in psoriatic arthritis.

INTRODUCTION: Eicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available. OBJECTIVE: Here, we intend to describe a detailed eicosanoid profiling in patients with psoriatic arthritis (PsA) and evaluate correlations with parameters of disease activity. METHODS: Forty-one patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum eicosanoids were determined by LC-MS, and the correlation between metabolite levels and disease scores was evaluated. RESULTS: Sixty-six eicosanoids were identified by reverse-phase LC/MS. Certain eicosanoids species including several pro-inflammatory eicosanoids such as PGE2, HXB3 or 6,15-dk,dh,PGF1a correlated with joint disease score. Several eicosapentaenoic acid (EPA)-derived eicosanoids, which associate with anti-inflammatory properties, such as 11-HEPE, 12-HEPE and 15-HEPE, correlated with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) as well. Of interest, resolvin D1, a DHA-derived anti-inflammatory eicosanoid, was down-regulated in patients with high disease activity. CONCLUSION: Both pro- and anti-inflammatory eicosanoids were associated with joint disease score, potentially representing pathways of harm as well as benefit. Further studies are needed to determine whether these eicosanoid species might also play a role in the pathogenesis of joint inflammation in PsA.

Choline metabolite, trimethylamine N-oxide (TMAO), is associated with inflammation in psoriatic arthritis.

OBJECTIVES: Dietary intake of choline has been linked to systemic inflammation through the microbial production of two metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO). Herein we explore the association between choline metabolites and inflammation in psoriatic arthritis (PsA) patients. METHODS: Thirty-eight patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum concentration of choline metabolites (choline, TMA, TMAO, betaine and carnitine) were determined by LC-MS, and metabolite levels associated with disease scores. RESULTS: Among the 38 PsA patients included, the mean DAS28PCR was 2.74±1.29. Twenty-seven patients had active skin disease, with an average BSA of 7.2±16.22. TMAO, but not TMA or choline, significantly correlated with measures of disease activity for both skin and peripheral joints. CONCLUSIONS: In our cohort, only TMAO, but not TMA, choline, betaine or carnitine, was associated with inflammation in PsA patients, establishing a mechanistic link between TMAO and PsA phenotypes. Future studies will explore the modulation of TMAO and disease severity in PsA.

Novel approaches to biological therapy for psoriatic arthritis.

INTRODUCTION: Improved understanding of the immunopathogenic mechanisms in psoriatic arthritis (PsA) has led to the development of targeted biological therapies, which demonstrate superior clinical efficacy to traditional disease-modifying antirheumatic drugs (DMARDs). There are currently 3 classes of biological agents that are approved for the treatment of psoriatic disease: tumor necrosis factor alpha inhibitors (TNFi), including etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol; ustekinumab, a monoclonal antibody (mAb) directed against interleukin (IL)-12 and IL-23; and secukinumab, a human anti-IL-17A mAb. Other agents are in development. Our growing experience with these medications has revolutionized the approach to disease management in PsA. AREAS COVERED: This article discusses the rationale for using biological therapies in PsA, highlighting clinical trial evidence that supports the use of these agents. We summarize novel treatment approaches using biological therapies in the management of PsA, including early intervention, targeted therapy, TNFi switching, combination therapy, and tapering or discontinuation of biological therapy. We conclude with a discussion of the importance comorbidities have on selection of therapy. EXPERT OPINION: The advent of highly effective biological therapies has revolutionized the management of patients with PsA. Growing experience with these agents has led to novel treatment approaches that may improve clinical outcomes for PsA patients.

Novel Treatment Concepts in Psoriatic Arthritis.

The introduction of highly effective therapies and clearly defined targets has altered the treatment paradigm in psoriatic arthritis (PsA). Validated classification criteria and outcome measures specific to PsA have helped standardize a therapeutic approach to this heterogeneous disease that affects multiple clinical domains. This article discusses the importance of early intervention using a treat-to-target strategy; emerging evidence for tight control based on minimal disease activity criteria; disease considerations specific to PsA (prognostic markers, biomarkers, subclinical disease, comorbidities); and new treatment strategies to deal with refractory disease (eg, tumor necrosis factor inhibitor switching and use of novel disease-modifying therapies) and controlled disease (eg, tapering or discontinuing biologic therapy).

Interleukin-17 inhibition in psoriatic arthritis.

Greater understanding of the underlying disease process has led to the development of targeted therapeutic agents and innovative strategies in the treatment of psoriatic arthritis (PsA). This report addresses novel medications targeting the T helper 17 cell pathway, specifically those inhibiting interleukin-17A and its receptor, and discusses their role as effective therapies in the management of PsA.

Trial design in psoriatic arthritis: what could be changed?

A greater understanding of the underlying disease process, combined with the development of novel therapeutic agents, has led to innovative strategies in the treatment of psoriatic arthritis (PsA). This report addresses unmet needs in clinical trial design in PsA, and proposes some amendments that may yield data that can potentially improve patient outcomes in the management of PsA.

Choosing wisely: the Canadian Rheumatology Association's list of 5 items physicians and patients should question.

OBJECTIVE: To develop a list of 5 tests or treatments used in rheumatology that have evidence indicating that they may be unnecessary and thus should be reevaluated by rheumatology healthcare providers and patients. METHODS: Using the Delphi method, a committee of 16 rheumatologists from across Canada and an allied health professional generated a list of tests, procedures, or treatments in rheumatology that may be unnecessary, nonspecific, or insensitive. Items with high content agreement and perceived relevance advanced to a survey of Canadian Rheumatology Association (CRA) members. CRA members ranked these top items based on content agreement, effect, and item ranking. A methodology subcommittee discussed the items in light of their relevance to rheumatology, potential effect on patients, and the member survey results. Five candidate items selected were then subjected to a literature review. A group of patient collaborators with rheumatic diseases also reviewed these items. RESULTS: Sixty-four unique items were proposed and after 3 Delphi rounds, this list was narrowed down to 13 items. In the member-wide survey, 172 rheumatologists responded (36% of those contacted). The respondent characteristics were similar to the membership at large in terms of sex and geographical distribution. Five topics (antinuclear antibodies testing, HLA-B27 testing, bone density testing, bone scans, and bisphosphonate use) with high ratings on agreement and effect were chosen for literature review. CONCLUSION: The list of 5 items has identified starting points to promote discussion about practices that should be questioned to assist rheumatology healthcare providers in delivering high-quality care.

The Relationship Between Function and Disease Activity as Measured by the HAQ and DAS28 Varies Over Time and by Rheumatoid Factor Status in Early Inflammatory Arthritis (EIA). Results from the CATCH Cohort.

OBJECTIVE: To investigate the relationship between function and disease activity in early inflammatory arthritis (EIA). METHODS: Canadian Early Arthritis Cohort (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3 months for the first year and then at 18 and 24 months. We also investigated the relationship between HAQ and DAS28 by age (<65 versus ≥65) and RF (positive vs negative). RESULTS: Mean HAQ and DAS28 scores were highest at the initial visit with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28 scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were significant at all time points (p<0.01). The correlations between HAQ and DAS28 were variable over time. The strongest correlation between HAQ and DAS28 occurred at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and 24 months (r=0.59, n=214). The baseline correlation between HAQ and DAS28 was significantly different than correlations obtained at 3, 6, and 12 months (p=0.02, 0.01, and 0.01, respectively). Age did not change the association between HAQ and DAS28 {<65 years old (r=0.50, n=868) versus ≥65 (r=0.48, n=254), p=0.49}. The correlation between HAQ and DAS28 was stronger with RF+ patients (r=0.63, n=636) vs RF negative (r=0.47, n=477), p=0.0043. CONCLUSION: Over 2 years in EIA, HAQ and DAS both improved; correlations at time points were different over 2 years and RF status affected the correlations.

Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumatoid arthritis at enrollment into a multi-site registry: results from the catch cohort.

We determined the prevalence of work disability in early rheumatoid arthritis (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR criteria versus those not meeting criteria, to determine the impact of meeting new criteria on work disability status. Data at first visit into the cohort were analyzed. Descriptive statistics and logistic regression analyses were performed to investigate the association of other variables in our database with work disability. 1,487 patients were enrolled in the CATCH study, a multi-site observational, prospective cohort of patients with EIA. 934 patients were excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP was absent, and 429 were not working for other reasons). Of the 553 patients included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %) were employed while 29 (5.2 %) reported work disability at first visit. There were no differences between those meeting 2010 ACR criteria versus those who did not. Baseline characteristics associated with work disability were male gender, age, education, income, HAQ, and positive RF status. The mean HAQ score in work disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001). Disease activity score (DAS28) was not associated with work disability (p = 0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global assessment, or SF-12v2. In the regression model, work disability was associated with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001), but not significantly associated with male gender (p = 0.08), older age (>50 years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found rates of work disability to be low at entry into this EIA cohort compared to previous studies. There may be potential for intervention in ERA to prevent the development of work disability.