Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. METHODS: JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. RESULTS: Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. CONCLUSIONS: Five trajectories of JIA disease activity, and associated baseline variables, were identified.

Race, ethnicity and patient-reported outcomes in childhood-onset systemic lupus erythematosus.

OBJECTIVES: This study assesses the association of race/ethnicity with the Patient-Reported Outcomes Measurement Information System (PROMIS®) in childhood-onset systemic lupus erythematosus (cSLE) patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: cSLE patients enrolled in the CARRA Registry within two years of cSLE diagnosis who met ACR and/or SLICC classification criteria for lupus were included. Baseline demographics, laboratory, and disease features as well as patient-reported outcomes were obtained. Multivariable linear regression analysis was used to examine the association of race and ethnicity with PROMIS scores at registry enrolment. RESULTS: 425 cSLE patients met inclusion criteria: 83.8% were female, 30.6% non-Hispanic White, 29.7% Black, 22.1% Hispanic. The mean age at diagnosis was 13.9 years (SD 2.5). Household income and highest parental education varied by race/ethnic group, as did frequency of rash, leukopenia, and anti-Smith antibodies. The cohort had low-moderate baseline disease activity (SLEDAI mean: 6.0 [SD 6.7]). The overall PROMIS Global Health mean T-score was 38.6 (SD 6.5), more than one standard deviation below the general population mean of 50. There was no association between race/ethnicity and PROMIS scores in multivariable linear regression analysis. CONCLUSIONS: In this multiethnic paediatric lupus cohort, PROMIS global health was lower when compared with the general paediatric US population. Moreover, PROMIS global health, pain interference, and physical function mobility did not vary across races/ethnicities.

Efficacy and Safety of Intravenous Golimumab in Ankylosing Spondylitis Patients With Early and Late Disease Through One Year of the GO-ALIVE Study.

BACKGROUND/OBJECTIVE: This post hoc analysis assessed efficacy and safety of intravenous (IV) golimumab in ankylosing spondylitis (AS) patients with early disease (ED) versus late disease (LD). METHODS: The phase 3, double-blind, GO-ALIVE study randomized patients to IV golimumab 2 mg/kg at weeks 0 and 4 and then every 8 weeks through week 52, or placebo at weeks 0, 4, and 12 with crossover to IV golimumab at week 16. Clinical efficacy was assessed by ≥20% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS20), ≥50% improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), and Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 (inactive disease). Using self-reported duration of inflammatory back pain (IBP), patients were grouped into quartiles: first = ED and fourth = LD. Descriptive statistics summarized efficacy and safety findings through 1 year. RESULTS: Early disease patients (n = 60) were ~10 years younger and had shorter median AS (IBP) symptom duration (2-3 years) versus LD patients (n = 52; 21-24 years). At week 16, numerically higher proportions of golimumab- than placebo-treated patients achieved ASAS20 (ED: 71% vs. 32%; LD: 67% vs. 21%), BASDAI 50 (ED: 40% vs. 12%; LD: 33% vs. 7%), and ASDAS <1.3 (ED: 17% vs. 4%; LD 8% vs. 0%) regardless of IBP duration. Efficacy was durable through 1 year of treatment; however, response rates were numerically higher in patients with ED versus LD. Through week 60, adverse events and serious adverse events, respectively, were reported by 46% and 3% of ED patients and 61% and 2% of LD patients. CONCLUSION: Prompt diagnosis of AS and early treatment with IV golimumab may yield more robust improvements in disease activity.

Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. METHODS: Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3-9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. RESULTS: We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. CONCLUSION: Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.

A new Canadian inception cohort for juvenile idiopathic arthritis: The Canadian Alliance of Pediatric Rheumatology Investigators Registry.

OBJECTIVES: The aim was to describe the design, methods and initial findings of a new Canadian inception cohort of children with JIA, The Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry. METHODS: The CAPRI JIA Registry was started in 2017 to collect information prospectively on children enrolled within 3 months of JIA diagnosis across Canada. The registry has a non-traditional modular design, with no artificially set times for registry visits to occur, streamlined multi-method data collection that requires 2-4 min per visit, and reports cumulative incidence of treatments, outcomes and adverse events calculated by Kaplan-Meier survival methods. RESULTS: A total of 166 patients, enrolled a median of 6 weeks after JIA diagnosis at 10 centres, were included. The median age at diagnosis was 9 years [interquartile range (IQR) 3, 13], 61% were female and 51% had oligoarticular JIA. The median three-variable clinical Juvenile Arthritis Disease Activity Score was 6.5 (IQR 4, 10) at enrolment, and the median time to first attainment of clinically inactive disease (CID) was 24 weeks (by 1 year, 81%). Within 1 year of diagnosis, 70% of patients had started a DMARD and 35% a biologic agent. The rates of adverse events and serious adverse events were 60 and 5.8 per 100 patient-years, respectively. CONCLUSION: This streamlined and flexible registry minimizes the burden of data collection and interference with clinic operations. Initial findings suggest that treatments for newly diagnosed patients with JIA in Canada have intensified, and now 81% of patients attain CID within 1 year of diagnosis.

Teens Taking Charge: A Randomized Controlled Trial of a Web-Based Self-Management Program With Telephone Support for Adolescents With Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a serious and potentially debilitating pediatric illness. Improved disease self-management may help to improve health outcomes. OBJECTIVE: This study aimed to evaluate the effectiveness of the Teens Taking Charge Web-based self-management intervention in reducing symptoms and improving health-related quality of life (HRQL) in adolescents with JIA compared with a Web-based education control condition. METHODS: Adolescents with JIA aged 12 to 18 years were recruited from 11 Canadian pediatric rheumatology centers. Caregivers were invited to participate along with their child. In addition to standard medical care, participants were randomized to receive either (1) the Teens Taking Charge self-management intervention or (2) a Web-based education control condition for a period of 12 weeks. Adolescents in the intervention group completed website modules addressing cognitive behavioral coping skills, stress management, and other self-management topics, while also receiving monthly telephone calls from a trained health coach. Adolescents in the education control group were instructed to view a series of preselected public JIA educational websites and received monthly calls from a coach who asked about their own best efforts at managing JIA. Caregivers in the intervention group completed website modules related to promoting independence and disease self-management in their child. Caregivers in the education control group were instructed to view a series of preselected public JIA educational websites. Outcome assessment occurred at baseline, 12 weeks (posttreatment), and at 6 and 12 months postrandomization. The primary outcomes were pain intensity, pain interference, and HRQL. Secondary outcomes were emotional symptoms, adherence, coping, knowledge, and self-efficacy. RESULTS: In total, 333 adolescents and 306 caregivers were enrolled. Significant overall reductions in pain intensity (P=.02) and pain interference (P=.007) were observed for intervention group participants compared with those in the education control group, after adjusting for baseline levels. There was a significant overall improvement in HRQL related to problems with pain (P=.02) and problems with daily activities (P=.01). There was also a significant difference in the intervention group over time (P=.008) for HRQL related to treatment problems, with the intervention group participants demonstrating improved HRQL by 12 months compared with education control group participants. Both groups showed nonsignificant improvements compared with baseline in other primary outcomes. There were no significant differences between the groups in any secondary outcomes or caregiver-reported outcomes. CONCLUSIONS: The results of this randomized trial suggest that the Teens Taking Charge Web-based intervention is effective at reducing both pain intensity and pain interference, as well as improving HRQL in adolescents with JIA, compared with education control. These effects are sustained for up to 12 months following program completion. The Teens Taking Charge program is now publicly available at no cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT01572896; https://clinicaltrials.gov/ct2/show/NCT01572896.

Testing population-based performance measures identifies gaps in juvenile idiopathic arthritis (JIA) care.

BACKGROUND: The study evaluates Performance Measures (PMs) for Juvenile Idiopathic Arthritis (JIA): The percentage of patients with new onset JIA with at least one visit to a pediatric rheumatologist in the first year of diagnosis (PM1); and the percentage of patients with JIA under rheumatology care seen in follow-up at least once per year (PM2). METHODS: Validated JIA case ascertainment algorithms were used to identify cases from provincial health administrative databases in Manitoba, Canada in patients < 16 years between 01/04/2005 and 31/03/2015. PM1: Using a 3-year washout period, the percentage of incident JIA patients with ≥1 visit to a pediatric rheumatologist in the first year was calculated. For each fiscal year, the proportion of patients expected to be seen in follow-up who had a visit were calculated (PM2). The proportion of patients with gaps in care of > 12 and > 14 months between consecutive visits were also calculated. RESULTS: One hundred ninety-four incident JIA cases were diagnosed between 01/04/2008 and 03/31/2015. The median age at diagnosis was 9.1 years and 71% were female. PM1: Across the years, 51-81% of JIA cases saw a pediatric rheumatologist within 1 year. PM2: Between 58 and 78% of patients were seen in yearly follow-up. Gaps > 12, and > 14, months were observed once during follow-up in 52, and 34%, of cases, and ≥ twice in 11, and 5%, respectively. CONCLUSIONS: Suboptimal access to pediatric rheumatologist care was observed which could lead to diagnostic and treatment delays and lack of consistent follow-up, potentially negatively impacting patient outcomes.

Validation of administrative case ascertainment algorithms for chronic childhood arthritis in Manitoba, Canada.

We validated case ascertainment algorithms for juvenile idiopathic arthritis (JIA) in the provincial health administrative databases of Manitoba, Canada. A population-based pediatric rheumatology clinical database from April 1st 1980 to March 31st 2012 was used to test case definitions in individuals diagnosed at ≤15 years of age. The case definitions varied the number of diagnosis codes (1, 2, or 3), time frame (1, 2 or 3 years), time between diagnoses (ever, >1 day, or ≥8 weeks), and physician specialty. Positive predictive value (PPV), sensitivity, and specificity with 95% confidence intervals (CIs) are reported. A case definition of 1 hospitalization or ≥2 diagnoses in 2 years by any provider ≥8 weeks apart using diagnosis codes for rheumatoid arthritis and ankylosing spondylitis produced a sensitivity of 89.2% (95% CI 86.8, 91.6), specificity of 86.3% (95% CI 83.0, 89.6), and PPV of 90.6% (95% CI 88.3, 92.9) when seronegative enthesopathy and arthropathy (SEA) was excluded as JIA; and sensitivity of 88.2% (95% CI 85.7, 90.7), specificity of 90.4% (95% CI 87.5, 93.3), and PPV of 93.9% (95% CI 92.0, 95.8) when SEA was included as JIA. This study validates case ascertainment algorithms for JIA in Canadian administrative health data using diagnosis codes for both rheumatoid arthritis (RA) and ankylosing spondylitis, to better reflect current JIA classification than codes for RA alone. Researchers will be able to use these results to define cohorts for population-based studies.

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. METHODS: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. RESULTS: 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. CONCLUSIONS: In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort.

OBJECTIVE: To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. METHODS: Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan-Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. RESULTS: In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46-57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. CONCLUSIONS: Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

The prevalence of systemic autoimmune rheumatic diseases in Canadian pediatric populations: administrative database estimates.

To estimate systemic autoimmune rheumatic disease (SARD) prevalence using administrative data for pediatric populations in four Canadian provinces. Physician billing claims and inpatient hospitalizations from Alberta, Manitoba, Quebec, and Saskatchewan were used to define cases aged ≤18 years with a SARD diagnosis code in: one or more hospitalization, two or more physician visits within 2 years and at least 2 months apart, or one or more physician visit to a rheumatologist. Estimates ranged from 15.9/100,000 in Quebec [95% confidence interval (95% CI) 14.1, 18.0] to 23.0/100,000 in Manitoba (95% CI 17.9, 29.2). SARDs were more common in females than in males across all provinces. There was a slightly higher prevalence among those living in urban compared to rural areas of Alberta (rate difference 14.4, 95% CI 8.6, 20.1) and Saskatchewan (rate difference 13.8, 95% CI 1.0, 26.6). Our results provide population-based prevalence estimates of pediatric SARDs in four Canadian provinces.

Chronic inflammatory arthritis prevalence estimates for children and adolescents in three Canadian provinces.

There is a paucity of published population-based estimates of the prevalence of chronic inflammatory arthritis in the pediatric population. We used administrative health data to estimate the prevalence of chronic inflammatory arthritis in individuals ≤18 years in three Canadian provinces: Quebec, Manitoba, and Saskatchewan. Cases aged ≤18 years were identified by meeting any one of the following criteria: (a) ≥1 hospital discharge abstract with an ICD-9 code of 714 or ICD-10-CA codes of M05, M06 or M08, or (b) ≥2 ICD-9 714 billing codes ≥8 weeks apart, but within 2 years, or (c) ≥1 ICD-9 714 billing code by a rheumatologist. Crude prevalence estimates per 10,000 population were estimated with 95 % confidence intervals (CIs). Prevalence estimates were 11.7 per 10,000 individuals ≤18 years of age in Manitoba, 9.8 per 10,000 in Saskatchewan, and 8.0 per 10,000 in Quebec. In pairwise comparisons of rate differences, Manitoba and Saskatchewan had higher estimates than Quebec. Prevalence estimates were higher for females than males, with a difference of 5.9 cases per 10,000 residents (95 % CI 5.1, 6.7). Saskatchewan was the only province with a higher estimate in urban compared to rural residents (5.2, 95 % CI 2.5, 8.0). Variations in provincial estimates may be due to differences in underlying population characteristics. Although these estimates have face validity and are in keeping with the range of previously published pediatric prevalence estimates, studies to establish the empiric validity of case-finding algorithms are needed to advance research in pediatric chronic disease epidemiology.

Validation of administrative health data for the pediatric population: a scoping review.

BACKGROUND: The purpose of this research was to perform a scoping review of published literature on the validity of administrative health data for ascertaining health conditions in the pediatric population (≤20 years). METHODS: A comprehensive search of OVID Medline (1946 - present), CINAHL (1937 - present) and EMBASE (1947 - present) was conducted. Characteristics of validation studies that were abstracted included the study population, health condition, topic of the validation (e.g., single diagnosis code versus case-finding algorithm), administrative and validation data sources. Inter-rater agreement was measured using Cohen's κ. Extracted data were analyzed using descriptive statistics. RESULTS: A total of 37 articles met the study inclusion criteria. Cohen's κ for study inclusion/exclusion and data abstraction was 0.88 and 0.97, respectively. Most studies validated administrative data from the USA (43.2%) and Canada (24.3%), and focused on inpatient records (67.6%). Case-finding algorithms (56.7%) were more frequently validated than diagnoses codes alone (37.8%). Five conditions were validated in more than one study: diabetes mellitus, inflammatory bowel disease, asthma, rotavirus infection, and tuberculosis. CONCLUSIONS: This scoping review identified a number of gaps in the validation of administrative health data for pediatric populations, including limited investigation of outpatient populations and older pediatric age groups.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

INTRODUCTION: 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). METHODS: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. RESULTS: Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). CONCLUSIONS: In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. TRIAL REGISTRATION: DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

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.

Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA). METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data. RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported. CONCLUSION: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Persistent Patient-Level Effect of Guselkumab at Consecutive 8-Week Dosing Visits and Over Time in Patients With Active Psoriatic Arthritis: Post Hoc Analysis of a 2-Year, Phase 3, Randomized, Controlled Study.

OBJECTIVE: Group-level analyses from the phase 3 DISCOVER-2 trial of guselkumab demonstrated robust and durable improvements across psoriatic arthritis (PsA) domains. To specifically evaluate continuous disease control in individual patients, persistence of clinically relevant improvements was assessed, both at consecutive guselkumab dosing visits and over time. METHODS: Post hoc analyses included biologic-naïve patients randomized to 100 mg of guselkumab at week 0, week 4, and then every 8 weeks (Q8W). Improvements in joint (minimal clinically important improvement [MCII] in Disease Activity Index for PsA [DAPSA; ≥7.25], clinical DAPSA [cDAPSA; ≥5.7]), skin (Investigator's Global Assessment [IGA] 0/1), and overall disease activity (patient global assessment of arthritis and psoriasis [PtGA Arthritis+Psoriasis; MCII ≥ 15 mm], PsA Disease Activity Score [PASDAS; MCII ≥ 0.8]) were assessed. Proportions of patients with maintenance of DAPSA and cDAPSA MCII at consecutive Q8W guselkumab dosing visits (ie, at weeks 4 and 12, weeks 12 and 20, etc through week 52) and patient-level durability of response through week 100 (Kaplan-Meier) were determined. RESULTS: Among 248 patients randomized to guselkumab Q8W, 93% to 99% maintained clinical improvement in joint disease at consecutive Q8W dosing visits through week 52 across time periods. Among guselkumab patients achieving MCII by week 24, estimated probabilities of maintenance of clinical improvement 100 weeks post achievement ranged from 68% (IGA 0/1) to 89% (PASDAS MCII). Median times to loss of improvement were not reached; estimated mean weeks of maintenance of improvement were 58.6, 52.4, 75.7, 83.6, and 76.7, respectively, for DAPSA, cDAPSA, IGA, PtGA Arthritis+Psoriasis, and PASDAS. CONCLUSION: Guselkumab provided highly durable patient-level improvements, both at consecutive Q8W dosing visits for joint disease activity and over time across PsA domains according to physician- and patient-driven assessments.

Improvements in Patient-Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real-World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Evaluate patient-reported outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: This analysis includes registry participants who initiated and persisted with on-label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (On-Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient-reported outcomes, including patient-reported pain (0-100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0-100 visual analog scale), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3). Unadjusted, nominal P values were calculated via single-proportion, one-sided test (H0 = 0%; α = 0.05). RESULTS: Of 90 On-Label Persisters, most had treatment-resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease-modifying antirheumatic drugs, respectively), with mean (SD) baseline patient-reported pain, PtGA, and HAQ-DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9 (0.6), respectively. Among those with patient-reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15-mm reductions at 6 months; among those with HAQ-DI scores of at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P < 0.001). CONCLUSION: Pain and physical function are important contributors to health-related quality of life. In this real-world population of patients with treatment-resistant PsA and 6 months of persistent guselkumab treatment, clinically meaningful improvements in pain and physical function were achieved by approximately 40% and 30% of patients, respectively.

Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors.

BACKGROUND: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). METHODS: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. RESULTS: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. CONCLUSION: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.