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.

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.

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.

Predictors of persisting pain in children with Juvenile Idiopathic Arthritis: a case control study nested in the ReACCh-Out cohort.

BACKGROUND: To identify baseline predictors of persisting pain in children with Juvenile Idiopathic Arthritis (JIA), relative to patients with JIA who had similar baseline levels of pain but in whom the pain did not persist. METHODS: We used data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) inception cohort to compare cases of 'moderate persisting pain' with controls of 'moderate decreasing pain'. Moderate pain was defined as a Visual Analogue Scale (VAS) for pain measurement score of > 3.5 cm. Follow-up was minimum 3 years. Univariate and Multivariate logistic regression models ascertained baseline predictors of persisting pain. RESULTS: A total of 31 cases and 118 controls were included. Mean pain scores at baseline were 6.4 (SD 1.6) for cases and 5.9 (1.5) for controls. A greater proportion of cases than controls were females (77.4% vs 65.0%) with rheumatoid factor positive polyarthritis (12.9% vs 4.2%) or undifferentiated JIA (22.6% vs 8.5%). Oligoarthritis was less frequent in cases than controls (9.7% vs 33%). At baseline, cases had more active joints (mean of 11.4 vs 7.7) and more sites of enthesitis (4.6 vs 0.7) than controls. In the final multivariate regression model, enthesitis count at baseline (OR 1.40, CI 95% 1.19-1.76), female sex (4.14, 1.33-16.83), and the overall Quality of My Life (QoML) baseline score (0.82, 0.69-0.98) predicted development of persisting pain. CONCLUSIONS: Among newly diagnosed children with JIA with moderate pain, female sex, lower overall quality of life, and higher enthesitis counts at baseline predicted development of persisting pain. If our findings are confirmed, patients with these characteristics may be candidates for interventions to prevent development of chronic pain.

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

INTRODUCTION: The aim of this work is to evaluate treatment persistence and clinical 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: Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired t tests determined changes that were statistically significantly different from 0 (α = 0.05). RESULTS: Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6 years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was - 5.4 (- 8.5, - 2.3; p < 0.001) at 6 months. Significant mean improvements in PGA (- 19.0 [- 24.2, - 13.8]), patient-reported pain (- 9.1 [- 14.4, - 3.8]), and %BSA (- 5.1 [- 7.6, - 2.7]) were also observed (all p < 0.001). CONCLUSIONS: In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6 months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms. TRIAL REGISTRATION: clinicaltrials.gov: NCT02530268.

Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study.

INTRODUCTION: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial. METHODS: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression. RESULTS: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52. CONCLUSIONS: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02186873.

Ankylosing spondylitis (AS) is a type of arthritis that mostly affects the spine. Patients with AS also often have severe fatigue. Intravenous (IV)-golimumab, which blocks the inflammatory action of tumor necrosis factor, is approved to treat AS. We used information from a clinical trial (GO-ALIVE) to determine whether IV-golimumab reduced fatigue in patients with AS, and if fatigue improvement was associated with improvement in other AS symptoms, including spinal pain, ability to function, and inflammation. In the 1-year GO-ALIVE study, patients were assigned to receive either IV-golimumab or placebo. Patients assigned to placebo were switched to IV-golimumab starting at week 16. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue question and the 36-Item Short Form Health Survey (SF-36) vitality subscale were used to assess fatigue. Improvement in AS symptoms was measured using the Assessment of SpondyloArthritis international Society ≥ 20% and ≥ 40%  improvement criteria (ASAS20 and ASAS40). After 16 weeks of treatment, patients treated with IV-golimumab, on average, had statistically significantly greater improvement in both measures of fatigue than patients treated with placebo. At 1 year, after the placebo group had received IV-golimumab starting at week 16, improvement in fatigue was similar between groups. Improvement in fatigue at week 16 increased the likelihood that ASAS20 and ASAS40 would be achieved at week 16. Similar results were observed at 1 year. Additionally, improvement in fatigue at week 16 predicted the likelihood of achieving ASAS20 and ASAS40 at 1 year. Together, these results demonstrate that IV-golimumab provided important, long-term improvement in fatigue in patients with AS that was positively associated with improvement in AS symptoms.

Effectiveness and safety of intravenous golimumab with and without concomitant methotrexate in patients with rheumatoid arthritis in the prospective, noninterventional AWARE study.

BACKGROUND: Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients. METHODS: AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year. RESULTS: Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (- 10.2 ± 14.2 and - 10.8 ± 13.8) and golimumab without MTX (- 9.6 ± 12.9 and - 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively. CONCLUSIONS: Mean change in CDAI score in the  golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. TRIAL REGISTRATION: clinicaltrials.gov NCT02728934 05/04/2016.

Response to Treatment with Intravenous Golimumab or Infliximab in Rheumatoid Arthritis Patients: PROMIS Results from the Real-World Observational Phase 4 AWARE Study.

INTRODUCTION: To assess changes in the Patient-Reported Outcomes Measurement Information System (PROMIS®) outcomes related to social, mental, and physical well-being after approximately 1 year of intravenous (IV) golimumab or infliximab treatment in patients with rheumatoid arthritis (RA) using real-world evidence from AWARE. METHODS: AWARE was a prospective, noninterventional, multicenter, observational, U.S.-based phase 4 study of 1270 RA patients who initiated treatment with IV golimumab or infliximab. PROMIS-29 and PROMIS short form (SF) Fatigue 7a and Pain Interference 6b questionnaires were administered at baseline and infusions 2, 5, and 8 (approximately weeks  4, 28, and 52 for IV golimumab and weeks  2, 22, and 46 for infliximab). Mean changes from baseline in all PROMIS-29 domains and respective SFs and response rates for achieving ≥ 3, ≥ 5, or ≥ 10-point improvements were determined. RESULTS: Among all patients, baseline mean ± SD PROMIS T-scores were consistent between treatment groups and indicated worse physical function (38.2 ± 6.8 IV golimumab, 38.0 ± 6.9 infliximab), more pain interference (63.0 ± 7.6 IV golimumab, 63.9 ± 7.8 infliximab), and greater fatigue (58.4 ± 9.9 IV golimumab, 59.4 ± 10.0 infliximab) in these patients vs the general U.S. population (T-score = 50). Through the 8th infusion of either treatment, IV golimumab- and infliximab-treated patients achieved meaningful improvements (≥ 3-point improvement in T-scores) in all PROMIS-29 domains and respective SFs, and the proportions of patients with ≥ 3, ≥ 5, or ≥ 10-point improvements in T-scores increased from infusion 2 through infusion 8. CONCLUSIONS: RA patients treated with IV golimumab or infliximab achieved comparable improvements across social, mental, and physical well-being PROMIS measures. Additionally, PROMIS detected meaningful clinical changes in patient-reported outcomes in both treatment groups. GOV REGISTRATION NUMBER: NCT02728934.

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.

Clinical Characteristics of Registry Participants with Psoriatic Arthritis Initiating Guselkumab: An Analysis from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

BACKGROUND: The monoclonal antibody guselkumab is the first selective inhibitor of the interleukin-23 p19 subunit approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). Given its recent approval for active PsA, data describing patients with PsA initiating guselkumab outside of clinical trials are limited. OBJECTIVE: This analysis describes characteristics of patients with rheumatologist-diagnosed PsA initiating guselkumab in the US-based, prospective, observational CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. METHODS: Demographics, lifestyle/disease characteristics, comorbidities, prior treatment, and disease activity were summarized for patients with PsA initiating guselkumab from registry inception through 30 September, 2021. RESULTS: Of 113 patients initiating guselkumab, the majority were female (63%), obese (67%), had psoriasis (89%), and initiated guselkumab as monotherapy (81%). Common comorbidities were hypertension (32%), depression (30%), and diabetes mellitus (26%). Mean tender (6.8) and swollen (2.0) joint counts, clinical Disease Activity Index for PsA score (19.1), and 57% of participants with ≥ 3% body surface area affected by psoriasis indicated moderate disease activity. Axial involvement was identified in 49% of patients. Median patient-reported pain and fatigue visual analog scale scores (0-100) were 60 and 59, respectively. Prior to guselkumab, 76% of patients had received two or more biologic disease-modifying antirheumatic drugs; the last therapy prior to guselkumab was a biologic disease-modifying antirheumatic drug in 81% of patients. CONCLUSIONS: Registry participants with PsA initiating guselkumab had active peripheral joint and skin disease, with substantial pain and fatigue; a considerable proportion had axial involvement. Future studies will evaluate the effectiveness of guselkumab in this population.

Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations.

OBJECTIVES: To describe the extrapolation approaches used to support intravenous (IV) golimumab for polyarticular juvenile idiopathic arthritis (pJIA) and juvenile psoriatic arthritis (jPsA) and subcutaneous (SC) ustekinumab for jPsA. METHODS: Pharmacokinetic, clinical response, and safety data from trials of IV golimumab and SC ustekinumab in polyarticular-course JIA (pc-JIA) (GO-VIVA) or pediatric psoriasis (PsO) (CADMUS and CADMUS Jr) and data from pivotal, phase 3 trials of these agents in adults with similar diseases were used to support extrapolation in pJIA and jPsA. In the phase 3 GO-VIVA trial, patients with pc-JIA aged 2 to < 18 years received IV golimumab 80 mg/m2 at weeks 0, 4, then every 8 weeks (Q8W). In the phase 3, randomized, placebo-controlled CADMUS trial, patients with PsO aged ≥ 12 to < 18 years received ustekinumab at weeks 0, 4, then Q12W. In the phase 3 CADMUS Jr trial, patients with PsO aged ≥ 6 to < 12 years received ustekinumab at weeks 0, 4, then Q12W. The ustekinumab analyses used data only from patients who received the standard ustekinumab dosing regimen (≤ 60 kg: 0.75 mg/kg; > 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg). RESULTS: In the 127 patients with pc-JIA treated with IV golimumab (GO-VIVA), pharmacokinetic and exposure-response results were similar to those in adults with rheumatoid arthritis treated with IV golimumab. Additionally, pharmacokinetic and clinical response data from five patients with jPsA in GO-VIVA were comparable to those in adults with PsA treated with IV golimumab. No new safety signals were observed in GO-VIVA. Pharmacokinetic and clinical response data observed in the four pediatric patients with PsO and jPsA treated with ustekinumab in CADMUS and CADMUS Jr were similar to those in the 91 pediatric patients with PsO without jPsA in these trials and to those in adults with PsA treated with ustekinumab. Safety was extrapolated from CADMUS or CADMUS Jr; no new signals were observed. CONCLUSIONS: These three sets of analyses corroborate similar exposure and efficacy of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in patients with jPsA to support extrapolation of established adult efficacy. The overall safety profiles of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in pediatric patients with PsO with or without jPsA were consistent with the safety profiles of these agents in the context of their clinical programs and cumulative use. Based on these analyses, the US Food and Drug Administration approved IV golimumab for polyarticular JIA and active PsA in patients 2 years and older and SC ustekinumab for pediatric PsA in patients 6 years and older, highlighting how use of an extrapolation approach can help streamline drug development for pediatric patient populations in whom larger clinical trials are not feasible. CLINICAL TRIAL REGISTRATION: GO-VIVA (NCT02277444) was registered at clinicaltrials.gov on 29 October 2014; CADMUS (NCT01090427) was registered on 22 March 2010; and CADMUS Jr (NCT02698475) was registered on 3 March 2016.

The Effect of Guselkumab on General Health State in Biologic-Naïve Patients with Active Psoriatic Arthritis Through Week 52 of the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Trial.

INTRODUCTION: In DISCOVER-2, guselkumab, an interleukin-23 p19 subunit inhibitor, was efficacious in biologic-naïve psoriatic arthritis (PsA) patients. We report the effect of guselkumab on health-related quality of life (HRQoL) using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and Visual Analog Scale (EQ-VAS) through Week 52. METHODS: Adults with active PsA were randomized to guselkumab 100 mg every 4 weeks (Q4W) or Weeks 0, 4, then every 8 weeks (Q8W), or placebo (crossover to guselkumab Q4W at Week 24). Least squares (LS) mean changes in EQ-5D-5L Index (0-1, US-based value set) and EQ-VAS (0-100) from baseline through Week 52 were assessed. Proportions of patients achieving minimally important differences (MIDs) were assessed through Week 52. Associations between patient clinical features and EQ-5D-5L Index and EQ-VAS scores were examined cross-sectionally with pooled data through Week 24. RESULTS: The analysis included 738 patients (Q4W n = 245; Q8W n = 248; placebo n = 245). At Week 24, LS mean changes from baseline in the Q4W, Q8W, and placebo groups were 0.12, 0.12, and 0.05, respectively, for EQ-5D-5L Index, and 18.2, 18.4, and 6.8, respectively, for EQ-VAS. At Week 52, improvement was maintained in the guselkumab groups and increased in the placebo crossover group. EQ-5D-5L Index MID was achieved by 56.0% in each guselkumab group at Week 24 and 66.2% in Q4W, 68.5% in Q8W, and 66.1% in placebo crossover group at Week 52. Higher C-reactive protein level, Psoriasis Area and Severity Index score, fatigue, and pain were correlated with worse EQ-5D-5L Index and EQ-VAS, based on pooled data through Week 24. Higher tender joint count was correlated with worse EQ-5D-5L, while higher swollen joint count was correlated with worse EQ-VAS. CONCLUSIONS: Guselkumab improved HRQoL through 52 weeks in patients with active PsA. Impairment in HRQoL was correlated with increased inflammation, fatigue, pain, and measures of skin and joint symptom severity. CLINICALTRIALS: GOV: NCT03158285.

The Effect of Guselkumab on Work Productivity in Biologic-Naïve Patients with Active Psoriatic Arthritis Through Week 52 of the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Trial.

INTRODUCTION: The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA). METHODS: Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains. RESULTS: In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W -20.1%, Q8W -19.6%, placebo -10.5%), work productivity (Q4W -20.1%, Q8W -19.2%, placebo -10.6%), and nonwork activity (Q4W -20.5%, Q8W -21.2%, placebo -9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1-25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism. CONCLUSION: Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03158285.

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.

Improvement in disease activity among patients with rheumatoid arthritis who switched from intravenous infliximab to intravenous golimumab in the ACR RISE registry.

Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR's Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6-9- and 9-12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6-9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9-12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI. Key Points • This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity. • Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch. • On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index. • These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab.

Effectiveness and Safety of High-Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance.

OBJECTIVE: To describe high-dose biologic use when treating juvenile idiopathic arthritis (JIA). METHODS: Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high-dose biologic use and characteristics of patients receiving high-dose biologics. We used regression modeling to compare 6-month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high-dose group) to those who initiated and remained on standard dosing (no-change group), and to those who switched biologic agents (biologic-switch group). We also compared serious adverse events (SAEs) between groups. RESULTS: A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high-dose biologic. There were no significant differences in outcomes between the high-dose group and the biologic-switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (-3.53 and -3.95, respectively; P = 0.68). Although the SAE rates in the high-dose group and the biologic-switch group were numerically higher than the no-change group, the event rates were similar, and neither rate was significantly higher than in the no-change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7-8.5] and 1.8 [95% CI 0.7-4.6], respectively). CONCLUSION: Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed.

Parent-Reported Medication Side Effects and Their Impact on Health-Related Quality of Life in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: To describe the frequency and severity of parent-reported medication side effects (SEs) in children with juvenile idiopathic arthritis (JIA) relative to physician-reported actionable adverse events (AEs), and to assess their impact on health-related quality of life (HRQoL). METHODS: Newly diagnosed JIA patients recruited between 2017 and 2019 to the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry were included. Parents reported presence and severity (0 = no problem, 10 = very severe) of medication SEs at every clinic visit. Physicians were asked to report any actionable AE. HRQoL was assessed using the Quality of My Life (QoML) questionnaire (0 = the worst, 10 = the best) and parent's global assessment (0 = very well, 10 = very poor). Analyses included proportion of visits with SEs or actionable AEs, cumulative incidence by Kaplan-Meier methods, and HRQoL impact measured with longitudinal mixed-effects models. RESULTS: SEs were reported at 371 of 884 (42%) visits (95% confidence interval [95% CI] 39, 45%) in 249 patients, with a median of 2 SEs per visit (interquartile range [IQR] 1-3), and median severity of 3 (IQR 1.5-5). Most SEs were gastrointestinal (32.5% of visits) or behavioral/psychiatric (22.4%). SE frequency was lowest with nonsteroidal antiinflammatory drugs alone (34.7%) and highest with prednisone and methotrexate combinations (66%). SE cumulative incidence was 67% (95% CI 59, 75) within 1 year of diagnosis, and 36% (95% CI 28, 44) for actionable AEs. Parent global and QoML scores were worse with SEs present; the impact persisted after adjusting for pain and number of active joints. CONCLUSION: Parents report that two-thirds of children with JIA experience SEs impacting their HRQoL within 1 year of diagnosis. SE mitigation strategies are needed in managing JIA.

Pharmacosurveillance in Juvenile Idiopathic Arthritis.

The advent of biologic disease-modifying antirheumatic drugs targeting specific cytokines or cell-cell interactions has dramatically changed the outlook of patients with juvenile idiopathic arthritis. However, safety concerns remain around the use of therapeutic agents for children with juvenile idiopathic arthritis. Foremost among these are the risks of serious infections and malignancy. This article provides an overview of methodologies for pharmacosurveillance in juvenile idiopathic arthritis, including spontaneous reporting systems and the use of diverse data sources, such as electronic health records, administrative claims, and clinical registries. The risks of infections and malignancies are then briefly reviewed.