Standardized reporting for systematic global evaluation of axial spondyloarthritis: An evidence-based and consensus-driven initiative.

INTRODUCTION: National and international scientific societies advocate for a regular, systematic, and standardized global evaluation of axial spondyloarthritis (axSpA) patients. However, there are no recommendations specifying the content of this global evaluation. This initiative aimed to propose a standardized reporting framework, using evidence-based and consensus approaches, to collect data on all domains of axSpA. METHODS: A literature review and consensus process involved a steering committee and an expert panel of 37 rheumatologists and health professionals. The first steering committee took place in March 2022 and identified the main domains for inclusion in the standardized report. A hierarchical literature review was conducted to identify items within these domains and tools for assessment. The items and tools for assessment were discussed and consensus was reached through a vote session during an expert meeting that took place in March 2023. RESULTS: The steering committee identified four main domains to include in the standardized reporting framework: disease assessment, comorbidities, lifestyle, and quality of life. Items and tools for assessment were adopted after the expert meeting. Additionally, recommendations regarding digital tools (websites, apps, social media) were provided. CONCLUSION: This initiative led to a consensus, based on evidence and expertise, on a reporting framework for use during periodic systematic global evaluations of axSpa in daily practice.

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS).

OBJECTIVE: To assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings. METHODS: This nationwide cohort study used the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database to identify all adults with PsA who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib) from 1 January 2015 to 30 June 2021. The primary outcome was a serious infection (ie, requiring hospitalisation), in a time-to-event analysis using propensity score-weighted Cox models, with adalimumab as the comparator, estimating weighted HRs (wHRs) and their 95% CIs. RESULTS: A total of 12 071 patients were included (mean age 48.7±12.7 years; 6965 (57.7%) women). We identified 367 serious infections (3.0% of patients), with a crude incidence rate of 17.0 per 1000 person-years (95% CI, 15.2 to 18.7). After inverse propensity score weighting and adjustment for time-dependent covariates and calendar year, risk of serious infection was significantly lower for new users of etanercept (wHR 0.72; 95% CI, 0.53 to 0.97) or ustekinumab (wHR, 0.57; 95% CI, 0.35 to 0.93) than adalimumab new users. This risk was not statistically modified with the other targeted therapies. CONCLUSIONS: The incidence of serious infection was low for PsA patients who were new users of targeted therapies in real-world settings. Relative to adalimumab new users, this risk was lower among new users of etanercept and ustekinumab and unmodified for the other molecules.

Impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab in axial spondyloarthritis (axSpA): data from the French multicentre retrospective FORSYA study.

OBJECTIVE: To compare the 1-year retention rate of secukinumab in axial spondyloarthritis (axSpA) and its predisposing factors with regard to its time of initiation (eg, right after or remotely from its launch). METHODS: Study design: Retrospective multicentre French study of patients with axSpA. Study periods: Two cohorts were evaluated regarding the time of initiation of secukinumab: cohort 1 (C1)-between 16 August 2016 and 31 August 2018-and cohort 2 (C2)-between 1 September 2018 and 13 November 2020. STATISTICAL ANALYSIS: The 1-year retention rate of secukinumab was estimated using the Kaplan-Meier method, and the log-rank test was used to compare the retention curves of the two cohorts. Preselected factors (eg, disease characterristics, line and time of secukinumab initiation) of secukinumab retention at 1 year were analysed by univariate and multivariate Cox model regression. RESULTS: In total, 906 patients in C1 and 758 in C2 from 50 centres were included in the analysis. The 1-year retention rate was better in C2 (64% (61%-68%)) vs C1 (59% (55%-62%)) (HR=1.19 (1.02-1.39); p=0.0297). In the multivariate analysis, the line of biologic therapy was the single predictive factor of the 1-year retention rate of secukinumab picked up in both cohorts, with a better retention rate when prescribed as first-line biologic therapy. CONCLUSION: The better secukinumab retention rate remotely from its launch is explained by its use at an earlier stage of the disease, suggesting a change in the behaviour of prescribing physicians. Our results emphasise the relevance of iterative evaluations of routine care treatments.

Erosions on T1-Weighted Magnetic Resonance Imaging Versus Radiography of Sacroiliac Joints in Recent-Onset Axial Spondyloarthritis: 2-Year Data (EMBARK Trial and DESIR Cohort).

OBJECTIVE: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907].

Ten-year clinical outcome of recent-onset axial spondyloarthritis: Results from the DESIR inception Cohort.

OBJECTIVES: This study aimed to evaluate the 10-year clinical outcome of patients with recent-onset axial spondyloarthritis (axSpA). METHODS STUDY DESIGN: The DESIR cohort is an inception cohort of axSpA patients. METHODS DIAGNOSIS AND MANAGEMENT: The diagnosis and management of patients were based on the decision of the treating rheumatologist. METHODS STATISTICAL ANALYSIS: Both complete cases and imputed data analyses were conducted. RESULTS: Of the 708 enrolled patients, 45 were excluded due to a change in the baseline diagnosis, 3 patients died, and 300 were lost to follow-up over the 10years. In the completer population, one patient required bilateral total hip replacement, and 56 patients received a pension due to invalidity. The prevalence of main extra-musculoskeletal features increased from baseline to year 10: psoriasis from 18% to 30%, acute anterior uveitis from 10% to 18%, and inflammatory bowel disease from 5% to 10%. The most frequent comorbidity was hypertension, with an increase from 5% to 15% from baseline to year 10. In the imputed data analysis the estimated proportions of patients with an acceptable status at year 10 were 70% [95% CI: 63; 77] for acceptable PASS, 43% [95% CI: 37; 49] for BASDAI<3, and 48% [95% CI: 41; 56] for ASDAS<2.1. CONCLUSION: These findings suggest that despite a quite favorable 10-year outcome exists for severe outcomes, a large proportion of patients present with an important disease burden reflected by patient-reported outcomes. This information can be valuable for providing patients with information at the time of diagnosis.

Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: a cohort study of 14 778 patients from the French health insurance database (SNDS).

BACKGROUND: Sex differences in phenotype presentation, disease trajectory and treatment response in psoriatic arthritis (PsA) have been reported. Nevertheless, whether classes of targeted therapies differentially affect men and women with PsA remains unclear. OBJECTIVES: To assess the effect of sex on the long-term persistence of each class of targeted therapies in PsA. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. We included all adults with PsA who were new users of targeted therapies (not in the year before the index date) during 2015-2021 and studied all treatment lines during the study period. Persistence was defined as the time from treatment initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by sex involved multivariate frailty models with conventional synthetic disease-modifying antirheumatic drugs and prednisone as time-dependant variables. RESULTS: We included 14 778 patients with PsA who were new users of targeted therapies: 8475 (57%) women (mean age 50±13 years; 15 831 lines), 6303 (43%) men (mean age 51±13 years; 10 488 lines). Overall, 1-year persistence was 52% for women and 62% for men and at 3 years it was 27% and 39%, respectively. After adjustments, persistence was lower for women than men for inhibitors of tumour necrosis factor (TNFi) (adjusted HR (HRa) 1.4, 99% CI 1.3 to 1.5) and interleukin 17 inhibitor (IL17i) (HRa 1.2, 99% CI 1.1 to 1.3) but not IL12/23i (HRa 1.1, 99% CI 0.9 to 1.3), IL23i (HRa 1.1, 99% CI 0.7 to 1.5) or Janus kinase inhibitor (JAKi) (HRa 1.2, 99% CI 0.9 to 1.6). CONCLUSION: The treatment persistence was lower for women than men for TNFi and IL17i but not for IL12/23i, IL23i or JAKi.

Bone marrow edema in the sacroiliac joints is associated with the development of structural lesions at the same anatomical location over time in patients with axial spondyloarthritis.

OBJECTIVE: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). METHODS: Patients with axSpA from the DESIR cohort with ≥2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evolution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: ≥5 erosions and/or fatty lesions on MRI-SIJ) was tested. RESULTS: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. CONCLUSIONS: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent structural damage, suggesting a cumulative effect.

Factors associated with the retention of secukinumab in patients with axial spondyloarthritis in real-world practice: results from a retrospective study (FORSYA).

BACKGROUND: Secukinumab efficacy and retention data are emerging in patients with axial spondyloarthritis (axSpA) in real-world settings. However, limited data are available on the predictive factors that affect the retention rate. The key objective was to determine whether objective signs of inflammation (OSI) were predictive of secukinumab retention at 1 year. METHODS: FORSYA is a French, multicentric, non-interventional, retrospective study in adult axSpA patients who received secukinumab treatment between its launch (11 August 2016) and 31 August 2018. The time to secukinumab discontinuation and retention were analysed using a Kaplan-Meier (KM) analysis. OSI was predefined by at least one of the criteria: C reactive protein ≥5 mg/L or erythrocyte sedimentation rate ≥28 mm/hour at secukinumab initiation or MRI inflammation at the sacroiliac or spine level. RESULTS: In total, 906 patients from 48 centres were included in the analysis, 42.2% of whom were men, with a mean age of 46.2±11.7 years and a mean disease duration of 9.3±9.1 years. The 1-year KM retention rate (95% CI) for secukinumab was 59% (55%-62%), whereas for patients with and without OSI, it was 58% (54%-62%) and 63% (53%-73%), respectively. In multivariate analysis, lack of prior exposure to tumour necrosis factor inhibitor (TNFi), absence of OSI and inflammatory bowel disease (IBD) were associated with a better retention of secukinumab at 1 year. CONCLUSION: Following its approval in France, ~59% of axSpA patients retained secukinumab in daily practice, at 1 year. Prior exposure to TNFi, OSI and IBD were identified as risk factors for secukinumab discontinuation.

Development and Validation of a Self-Administered Questionnaire Measuring Essential Knowledge in Patients With Axial Spondyloarthritis.

OBJECTIVE: To develop and validate a patient knowledge questionnaire regarding axial spondyloarthritis (axSpA). METHODS: Knowledge considered essential for patients with axSpA was identified through Delphi rounds among rheumatologists, healthcare professionals (HCPs), and patients, then reformulated to develop the knowledge questionnaire. Cross-sectional validation was performed in 14 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin concordance correlation coefficient), and sensitivity to change (knowledge score before vs after patient education sessions and effect size). RESULTS: The Spondyloarthritis Knowledge Questionnaire (SPAKE) is a self-administered 42-item questionnaire with a 32-item short form, both scored 0 to 100, assessing knowledge of disease, comorbidities, pharmacological treatments, nonpharmacological treatments, self-care, and adaptive skills. In the validation study (130 patients; 67 [51.5%] male, mean age 43.5 [SD 12.9] yrs), the mean (SD) score of the long-form questionnaire was 71.6 (15.4), with higher scores (better knowledge) in nonpharmacological treatments and adaptive skills and lower scores in cardiovascular comorbidity and pharmacological treatments. Acceptability was good, with no missing data; the internal validity coefficient was 0.85. Reproducibility was good (0.81, 95% CI 0.72-0.89). SPAKE showed good sensitivity to change; scores were 69.2 (15.3) then 82.7 (14.0) after patient education sessions (Hedges effect size = 0.92, 95% CI 0.52-1.31). CONCLUSION: SPAKE is a knowledge questionnaire for patients with axSpA, developed with the involvement of HCPs and patients and reflecting current recommendations for the management of axSpA. SPAKE will be useful in assessing knowledge acquisition and self-management strategies in routine care and research.

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients.

BACKGROUND: Paradoxical reactions (PRs) are defined as the occurrence during biologic therapy of a pathological condition that usually responds to these drugs. OBJECTIVES: To estimate the incidence of PRs and identify risk factors. METHODS: Multicentre study of the database for the Greater Paris University Hospitals, including biologic-naive patients receiving anti-tumour necrosis factor-α, anti-interleukin-12/23, anti-interleukin-17 or anti-α4ß7-integrin agents for psoriasis, inflammatory rheumatism or inflammatory bowel disease (IBD). We used natural language processing algorithms to extract data. A cohort and a case-control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors. RESULTS: Most of the 9303 included patients (median age 43·0, 53·8% women) presented an IBD (3773, 40·6%) or a chronic inflammatory rheumatic disease (3708, 39·9%), and 8489 (91·3%) received anti-TNF-α agents. A total of 297 (3·2%) had a PR. The global incidence rate was 7·6 per 1000 person-years [95% confidence interval (CI) 6·8-8·5]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1·9, 95% CI 1·1-3·2, P = 0·021] and a combination of at least two inflammatory diseases (aOR 6·1, 95% CI 3·6-10·6, P < 0·001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0·6, 95% CI 0·4-0·8, P = 0·002; and OR 0·4, 95% CI 0·2-0·6, P = 0·002, respectively). CONCLUSIONS: The likelihood of PRs was associated with IBD or a combination of a least two inflammatory diseases. More studies are needed to assess the benefit of systematically adding csDMARDs for such high-risk patients. What is already known about this topic? Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-α agents. Few data are available for other paradoxical reactions and the most recent biologics. What does this study add? Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases. Risk of paradoxical reactions was reduced with conventional synthetic disease-modifying antirheumatic drugs or corticosteroid therapy, which could be added for high-risk patients.

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database.

Increasing number of Janus kinase (JAK) inhibitors have been approved for chronic haematopoietic neoplasms and inflammatory/autoimmune diseases. We aimed to assess safety of the first three approved JAK inhibitors: ruxolitinib, tofacitinib and baricitinib. In this retrospective observational study, pharmacovigilance data were extracted from the World Health Organization database. Adverse events are classified according to Medical Dictionary for Regulatory Activities hierarchy. Until February 28, 2021, all Individual Case Safety Reports [ICSRs] with the suspected drug ruxolitinib, tofacitinib or baricitinib were included. Disproportionality analysis was performed and the information component (IC) was estimated. Adverse events were considered a significant signal if the lower end of the 95% credibility interval of the IC (IC025) was positive. We identified 126,815 ICSRs involving JAK inhibitors. Ruxolitinib, tofacitinib and baricitinib were associated with infectious adverse events (IC025 1.7, especially with viral [herpes and influenza], fungal, and mycobacterial infectious disorders); musculoskeletal and connective tissue disorders (IC025 1.1); embolism and thrombosis (IC025 0.4); and neoplasms (IC025 0.8, especially malignant skin neoplasms). Tofacitinib was associated with gastrointestinal perforation events (IC025 1.5). We did not find a significant increase in the reporting of major cardiovascular events. We identified significant association between adverse events and ruxolitinib, tofacinitib and baricitinib in international pharmacovigilance database.

Long-term Persistence of First-line Biologics for Patients With Psoriasis and Psoriatic Arthritis in the French Health Insurance Database.

Importance: Treatment options for psoriasis (PsO) and psoriatic arthritis (PsA) have evolved significantly throughout the era of biologics. Clinical trials are inadequate to assess the relative long-term efficacy of biologics and are often insufficient regarding safety. Objectives: To assess the long-term persistence of different biologic classes to treat PsO and PsA. Design, Setting, and Participants: This nationwide cohort study involved the administrative health care database of the French health insurance scheme linked to the hospital discharge database. All adults with PsO and PsA who were new users of biologics (not in the year before the index date) from January 1, 2015, to May 31, 2019, were included and followed up through December 31, 2019. Patients hospitalized for PsA in the PsO cohort and for PsO in the PsA cohort in the year before the index date were excluded. Data were analyzed from June 1 to October 31, 2021. Main Outcomes and Measures: Persistence was defined as the time from biologic therapy initiation to discontinuation and was estimated using the Kaplan-Meier method. Comparison of persistence by biologic class involved using propensity score-weighted Cox proportional hazards regression models and adjustment on specific systemic nonbiologics (time-dependent variables). Results: A total of 16 892 patients with PsO were included in the analysis (mean [SD] age, 48.5 [13.8] years; 9152 men [54.2%] men). Of these, 10 199 patients (60.4%) started therapy with a tumor necrosis factor (TNF) inhibitor; 3982 (23.6%), with an interleukin 12 and interleukin 23 (IL-12/23) inhibitor; and 2711 (16.0%), with an interleukin 17 (IL-17) inhibitor. An additional 6531 patients with PsA (mean [SD] age, 49.1 [12.8] years; 3565 [54.6%] women) were included; of these, 4974 (76.2%) started therapy with a TNF inhibitor; 803 (12.3%), with an IL-12/23 inhibitor; and 754 (11.5%), with an IL-17 inhibitor. Overall 3-year persistence rates were 40.9% and 36.2% for PsO and PsA, respectively. After inverse probability of treatment weighting and adjustment, the IL-17 inhibitor was associated with higher persistence compared with the TNF inhibitor for PsO (weighted hazard ratio [HR], 0.78 [95% CI, 0.73-0.83]) and PsA (weighted HR, 0.70 [95% CI, 0.58-0.85]) and compared with the IL-12/23 inhibitor for PsA (weighted HR, 0.69 [95% CI, 0.55-0.87]). No difference between the IL-17 inhibitor and IL-12/23 inhibitor for PsO was noted. The IL-12/23 inhibitor was associated with higher persistence than the TNF inhibitor for PsO (weighted HR, 0.76 [95% CI, 0.72-0.80]), with no difference observed for PsA. Conclusions and Relevance: The findings of this cohort study suggest that IL-17 inhibitors are associated with higher treatment persistence than the TNF inhibitor for PsO and PsA. Interleukin 17 inhibitors were also associated with higher persistence than the IL-12/23 inhibitor for PsA, with no difference for PsO. However, the persistence rates of all biologics remained globally low at 3 years.