Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.

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. METHODS: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. RESULTS: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). CONCLUSION: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Residual Disease Activity In Canadian Patients With Psoriatic Arthritis (PsA) Treated With Advanced Therapies: Results From A Multi-Registry 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 multi-region, observational, retrospective analysis of patient data extracted from the Rhumadata™ and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing de-identified 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: 1,596 patients were included. The proportion of patients who failed to achieve MDA within 6 months of an advanced therapy was 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Québec and 75.0% in the Atlantic/East region. Failure to achieve MDA was higher amongst patients receiving an IL-17i compared with a TNFi in all regions except Atlantic/East. Between 73.2 to 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24.0% in the West to 83.3% in the Atlantic/East. CONCLUSION: There is substantial burden and unmet need for improved therapies for Canadians living with PsA. There is a wide regional variation in outcomes that requires further assessment.

Work Productivity and General Health Through 2 Years of Guselkumab Treatment in a Phase 3 Randomized Trial of Patients With Active Psoriatic Arthritis.

INTRODUCTION: 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. METHODS: Adult patients with PsA were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W); at weeks 0, 4, then every 8 weeks (Q8W); or placebo (through week 24 with crossover to guselkumab Q4W). Work productivity and nonwork daily activity impairment were assessed using the Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) and patient-reported general health status using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and EQ-Visual Analog Scale (EQ-VAS). Least-squares (LS) mean changes from baseline in WPAI-PsA domains and EQ-5D-5L/EQ-VAS were assessed through week 100. Changes in employment status were utilized to estimate potential indirect savings from improved work productivity. RESULTS: Of 739 randomized patients, 738 had available baseline data for the analyses (Q4W 245; Q8W 248; placebo 245). At week 24, greater improvements in work productivity, nonwork daily activity, and EQ-5D-5L/EQ-VAS were observed in the Q4W and Q8W groups versus the placebo group. At week 100, LS mean reductions in work productivity impairment (- 23.8% to - 28.0%) and nonwork daily activity impairment (- 26.6% to - 29.2%) and improvements in EQ-5D-5L/EQ-VAS (0.14 to 0.15/21.2 to 25.0) were maintained in patients receiving guselkumab. Among patients employed at baseline, 12.1-16.4% were not employed at week 100, and 20.0-25.3% shifted from not employed at baseline to employed at week 100. Potential yearly indirect cost savings (USD) from improved work productivity at week 100 ranged from $16,529 to $19,409. CONCLUSION: Patients with active PsA treated with guselkumab demonstrated reduced impairment in work productivity and nonwork daily activity, together with improvement in general health status and substantial potential cost savings, over a 2-year period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03158285.

Use of Apremilast to Achieve Psoriatic Arthritis Treatment Goals and Satisfaction at 1 Year in the Canadian Real-World APPRAISE Study.

INTRODUCTION: 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. METHODS: APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per routine care between July 2018 and March 2020. Patients were followed for 12 months with visits suggested every 4 months. The primary outcome measure was achievement of remission (REM) or low disease activity (LDA), defined as a Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score ≤ 13. RESULTS: Of the 102 patients who enrolled, 45 (44.1%) discontinued the study by 12 months. Most patients (75.5%) had moderate or high disease activity, and 24.5% were in REM/LDA at baseline based on cDAPSA score. Achievement of cDAPSA REM/LDA was 63.7%, 67.2%, and 53.8% at months 4, 8, and 12, respectively. In those continuing in the study, significant improvements were seen in swollen and tender joint counts, pain visual analog scale, psoriasis body surface area, and complete dactylitis resolution. Enthesitis reduction was also observed. Improvements in treatment satisfaction and patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and the 36-item Short Form physical and mental component scores, were observed over 12 months. The proportion of patients achieving a Patient-Acceptable Symptom State (PASS) increased significantly from baseline at months 4, 8, and 12 (P < 0.001). Apremilast was well tolerated; the most frequent adverse events (AEs) leading to discontinuation were diarrhea (9/102 [8.8%]), nausea (4/102 [3.9%]), and migraine (4/102 [3.9%]). CONCLUSION: In this real-world study conducted in Canadian rheumatology clinics, apremilast demonstrated clinical effectiveness in patients with active PsA, along with patient satisfaction with treatment. Safety findings were consistent with previously reported clinical data. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03608657.

Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL.

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 VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52. RESULTS: A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to |52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52. CONCLUSIONS: Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.

Validity and score interpretation of the 12-item Psoriatic Arthritis Impact of Disease: an analysis of pooled data from two phase 3 trials of bimekizumab in patients with psoriatic arthritis.

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 with active PsA enrolled in two randomised controlled trials of bimekizumab (BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581)) were used to assess construct validity (correlations with other patient-reported outcomes), known-groups validity (based on Minimal Disease Activity index, Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score), reliability (Cronbach's alpha and intraclass correlation coefficients (ICCs)) and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor-based and distribution-based analyses, and symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses. RESULTS: The mean (SD) PsAID-12 total score at baseline was 4.19 (1.94). PsAID-12 scores demonstrated good convergent validity and good known-groups validity. Internal consistency reliability (Cronbach's alpha 0.95) and test-retest reliability (ICC ≥ 0.70) were also good. Responsiveness was acceptable (correlations ≥0.30 for most scores). Improvement thresholds were estimated at 1.5-2 points for the PsAID-12 total score and 2 or 3 points for item scores. Thresholds for different levels of symptom/impact severity could be derived for most PsAID-12 items. CONCLUSIONS: The PsAID-12 demonstrated robust psychometric properties in a large sample of patients with active PsA, supporting its use as a fit-for-purpose patient-reported outcome in this population. Furthermore, thresholds for score interpretation were derived.

Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis.

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 exploratory cohort to assess the association between NET remnant levels and the presence of active LN, and a separate LN cohort to determine the utility of NET remnants to predict renal outcomes over the subsequent 24 months. RESULTS: Ninety-two individuals were included in the exploratory cohort (49 active systemic lupus erythematosus (SLE), 23 inactive SLE and 20 healthy controls (HC)). NET remnants were significantly higher in patients with SLE patients compared with HC (p<0.0001 for both complexes) and those with active LN (36%) had significantly higher levels of NET remnants compared with active SLE without LN (Elastase-DNA: p=0.03; HMGB1-DNA: p=0.02). The LN cohort included 109 active LN patients. Patients with proliferative LN had significantly higher levels of NET remnants than non-proliferative LN (Elastase-DNA: p<0.0001; HMGB1-DNA: p=0.0003). Patients with higher baseline levels of NET remnants had higher odds of not achieving complete remission (Elastase-DNA: OR 2.34, p=0.007; HMGB1-DNA: OR 2.61, p=0.009) and of progressing to severe renal impairment (Elastase-DNA: OR 2.84, p=0.006; HMGB1-DNA: OR 2.04, p=0.02) at 24 months after the flare. CONCLUSIONS: Elastase-DNA and HMGB1-DNA complexes predict renal outcomes, suggesting they could be used to identify patients requiring more aggressive therapy at flare onset.

Comparative efficacy and safety of bimekizumab in psoriatic arthritis: a systematic literature review and network meta-analysis.

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 update conducted on 01 January 2023) identified randomised controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and tumour necrosis factor inhibitor (TNFi) -experienced (exp) patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. RESULTS: The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-exp patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th, and 3rd for American College of Rheumatology response (ACR)20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd, and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index [PASI]90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-exp patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. CONCLUSION: Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin, and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA.

Derivation and Internal Validation of a Disease-Specific Cardiovascular Risk Prediction Model for Patients With Psoriatic Arthritis and Psoriasis.

OBJECTIVE: To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-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 cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. RESULTS: Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9-89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0-89.1). CONCLUSION: Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration.

EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

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 predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

Different Immunologic Profiles Are Associated With Distinct Clinical Phenotypes in Longitudinally Observed Patients With Systemic Lupus Erythematosus.

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 populations within the peripheral blood of 16 healthy controls, 25 patients with clinically quiescent SLE, and 46 patients with SLE experiencing a flare at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify patients with similar immune profiles and to track changes over time. Parametric or nonparametric statistics were used when appropriate to assess the association of cellular phenotypes with clinical and laboratory parameters. RESULTS: Five clusters of patients were identified that variably contained patients with active and quiescent SLE, and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper (Th ) cells in the absence of B cell changes, or who had increased Th 1 cells and innate immune populations, mostly developed quiescent SLE on follow-up. A significant proportion of patients with SLE had depletion of many immune populations at flare and only showed increases in these populations post-flare. CONCLUSION: Cellular phenotyping of patients with SLE reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

Patient clusters identified by machine learning from a pooled analysis of the clinical development programme of secukinumab in psoriatic arthritis, ankylosing spondylitis and psoriatic arthritis with axial manifestations.

OBJECTIVES: To identify patient clusters based on baseline demographics and clinical indicators. METHODS: Pooled baseline demographics and clinical data of secukinumab-treated patients from ten Phase III studies in psoriatic arthritis (PsA; FUTURE 1-5 and MAXIMISE), ankylosing spondylitis (AS; MEASURE 1-4), were analysed by machine learning (ML) algorithms. The longitudinal responses of secukinumab 300 mg versus 150 mg were investigated across the clusters and three clinical indicators of tender joints, swollen joints and enthesitis. RESULTS: 3907 patients were grouped into eight distinct clusters based on patient demographics and baseline clinical characteristics. Patients with PsA and axial manifestations (MAXIMISE) were overrepresented in clusters 6-8. Patients in cluster 6 (mean age 48 years; 46% male) were overweight with pronounced psoriasis, higher articular burden in knees, shoulders, elbows and wrists. Patients in cluster 7 (mean age 47 years; 53% male) were less overweight with lower polyarticular joint counts and tenderness of the joints of the feet, wrists and hands. Patients in cluster 8 were predominantly with AS (mean age 43 years; 64% male) with a mean body mass index of 27.3 kg/m2, oligoarthritis and high prevalence of spinal pain. Patients with PsA (FUTURE) were overrepresented in clusters 1-5. Longitudinal analysis showed improvements with secukinumab 300 mg versus 150 mg in clusters 6 and 8 for tender joint counts, and cluster 7 for swollen joint counts. CONCLUSIONS: PsA clusters obtained by ML in pooled dataset indicate phenotypical heterogeneity of patients with PsA and axial manifestations and overlapping features across the spondyloarthritis spectrum.

Incidence and predictors of demyelinating disease in spondyloarthritis: data from a longitudinal cohort study.

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 or absence of DD. Incidence rates (IR) of DD were obtained with competing risk analysis. Cox regression analysis with Fine and Grey's method was used to evaluate predictors of DD development. RESULTS: Among 2260 patients with follow-up data, we identified 18 DD events corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, p= 0.01). The risk factors retained in the best predictive model for DD development included ever- (versus never-) smoking (HR 2.918, 95% CI 1.037-8.214, p= 0.0426), axSpA (versus PsA) (HR 8.790, 95% CI 1.242-62.182, p= 0.0294), and presence (versus absence) of IBD (HR 5.698, 95% CI 2.083-15.589, p= 0.0007). History of TNFi therapy was not a predictor of DD. CONCLUSION: The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNFi use was not found to be a predictor of DD in this cohort.

Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study.

INTRODUCTION: 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-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. METHODS: DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. RESULTS: Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6-1.7 for ASDAS; 49-54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100. CONCLUSIONS: Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03158285.

Psoriatic Arthritis and COVID-19: Patient Perspectives in a Large Psoriatic Arthritis Cohort.

OBJECTIVE: To estimate the prevalence of coronavirus disease 2019 (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 2021 and September 2021 in patients with PsA who had consented to email contact. The survey was completed by 152/193 (79%) patients who had consented to the study. RESULTS: There were 86 (56.6%) men and 66 (43.4%) women with a mean age of 58 years and mean disease duration of 19 years. During the pandemic, the mean patient-reported symptom severity was 4.10, 3.24, and 3.72 for joint, skin, and overall symptom severity, respectively. Seventy-four percent of respondents would accept the effect of their PsA over the past month for the next few months. Of 79 patients who were tested for severe acute respiratory syndrome coronavirus 2, 4 tested positive. All 4 were admitted to hospital; 2 required oxygen. One hundred fifty-one patients (99%) had received at least 1 vaccine dose. Fifty-nine (38.8%) participants believed their PsA medications increased their COVID-19 infection risk. Of the 130 patients who had a telemedicine assessment, 83.1% were happy with their virtual consultations. Most were happy to continue with virtual consultations until the pandemic resolved. The average satisfaction level regarding pandemic care was 7.87 on a sliding 10-point scale. CONCLUSION: COVID-19 prevalence was low among our patients. Patients were satisfied with their care during the pandemic. Most patients would happily continue with virtual care for the duration of the pandemic.

Derivation of a Multivariable Psoriatic Arthritis Risk Estimation Tool (PRESTO): A Step Towards Prevention.

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 psoriasis patients without PsA at enrollment. Participants were assessed annually by a rheumatologist for the development of PsA. Information about their demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms was used to develop prediction models for PsA. Penalized binary regression models were used for variable selection while adjusting for psoriasis duration. Risks of developing PsA over 1- and 5-year time periods were estimated. Model performance was assessed by the area under the curve (AUC) and calibration plots. RESULTS: Among 635 psoriasis patients, 51 and 71 developed PsA during the 1-year and 5-year follow-up periods, respectively. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (AUC 72.3). The risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesion, psoriasis severity, fatigue, pain, and use of systemic nonbiologic medication or phototherapy (AUC 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities. CONCLUSIONS: The development of PsA within clinically meaningful time frames can be predicted with reasonable accuracy for psoriasis patients using readily available clinical variables.

Proceedings of the GRAPPA 2022 Executive Retreat.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) leadership congregated for a strategic planning meeting before the 2022 GRAPPA annual meeting in New York, USA. Meeting aims were to review GRAPPA's performance in relation to its 2016 goals and identify successes and areas for further improvement, identify key GRAPPA priorities and activities for the next 5 years, and explore committee structures to best support these aims.

Proceedings of the Collaborative Research Network Meeting at the GRAPPA 2022 Annual Meeting.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting, the Collaborative Research Network (CRN) met to present updates on several projects. These included the GRAPPA-Industry biomarker projects, Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Axial Involvement in Psoriatic Arthritis Cohort (AXIS) study, and the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES). The meeting concluded with a discussion on pathways to further academia-industry collaboration.

Prediction of Psoriatic Arthritis in Patients With Psoriasis Using DNA Methylation Profiles.

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 methylation can potentially trigger and maintain PsA pathophysiological processes. We aimed to identify DNA methylation markers that can predict which patients with psoriasis will develop PsA prior to the onset of musculoskeletal symptoms. METHODS: Genome-wide DNA methylation was assessed in blood samples from patients with psoriasis who went on to develop arthritis (converters) and patients with psoriasis who did not (biologic naive, matched for age, sex, psoriasis duration, and duration of follow-up). Methylation differences between converters and nonconverters were identified by a multivariate linear regression model including clinical covariates (age, sex, body mass index, smoking). Predictive performance of methylation markers was assessed by developing support vector machine classification models with and without the addition of clinical variables. RESULTS: We identified a set of 36 highly relevant methylation markers (false discovery rate: adjusted P < 0.05 and a minimum change in methylation of 0.05) across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the receiver operating characteristic curve of 0.9644. CONCLUSION: This study shows that DNA methylation patterns at an early stage of psoriatic disease can distinguish between patients who will develop PsA from those who will not during the same follow-up.

Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort.

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) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. RESULTS: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244-566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80-6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05-3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43-20.39). CONCLUSION: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality.