vdH-S Score Research Articles

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment

ObjectiveAssess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA).MethodPost hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman’s coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100.ResultsBaseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [β] = 0.17–0.18, p < 0.03) and vdH-S score (β = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (β = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100).ConclusionsIn guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage.Key Points• Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA).• Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage.

Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3,...

The effect of guselkumab on inhibiting radiographic progression in patients with active psoriatic arthritis: study protocol for APEX, a Phase 3b, multicenter, randomized, double-blind, placebo-controlled trial

BackgroundGuselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.MethodsPatients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.DiscussionDISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.Trial registrationThis trial was registered at ClinicalTrials.gov, NCT04882098. Registered on 11 May 2021.

POS1027 EFFICACY AND SAFETY OF GUSELKUMAB, A MONOCLONAL ANTIBODY SPECIFIC TO THE p19-SUBUNIT OF INTERLEUKIN-23, THROUGH 2 YEARS: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

Background:Guselkumab (GUS), a selective IL-23 inhibitor dosed every 4 or 8 weeks (Q4W or Q8W), demonstrated efficacy for joint and skin symptoms, inhibition of structural damage progression (Q4W), and safety vs. placebo (PBO) through Week 24 (W24) of the Ph3, double-blind, PBO-controlled trial in biologic-naïve pts with PsA (DISCOVER-2).1 Favorable benefit-risk was also seen through 1 year.2Objectives:To assess GUS efficacy and safety through 2 years.Methods:Biologic-naïve adults with active PsA (≥5 swollen joint count [SJC] + ≥5 tender joint count [TJC]; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. Clinical efficacy (ACR/PASI/IGA/HAQ-DI) was assessed in the modified intention to treat (mITT) population through W100 with missing data imputation (nonresponse for categorical endpoints; no change/multiple imputation for continuous endpoints). Observed PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52, W100 (or at discontinuation [d/c]) and adverse events (AEs) through W112 were collected.Results:712/739 (96%) randomized pts continued study agent at W24; 687/739 (93%) continued at W52; 652/739 (88%) completed W100. ACR20 response rates in the mITT population continued to increase after W24, and at W100 were 76% for Q4W and 74% for Q8W (Figure 1). Similar response patterns were seen for ACR50/70, HAQ-DI and PASI90/100 (Table 1), and IGA0/1 and PASI75 response rates were consistent through W100 in pts randomized to Q4W and Q8W; W100 data for PBO→Q4W pts were consistent with pts treated with Q4W and Q8W (Table 1). GUS improvements in SF-36 PCS/MCS at W52 also persisted through W100 (data not shown). Low rates of radiographic progression (as measured by PsA-modified vdH-S scores) were observed during W52-100 for Q4W (n=227; 0.75) and Q8W (n=232; 0.46). In the PBO→Q4W group (n=228), radiographic progression was 1.12 during W0-24 (while on PBO), 0.51 during W24-100 (while on Q4W), and 0.13 during W52-100. Through W112, the incidences of AEs, serious AEs (SAEs), AEs leading to d/c, infections, serious infections, and injection site reactions were generally consistent with the PBO-controlled period and through 1 year. Of the pts in the Q4W (n=245), Q8W (n=248), and PBO→Q4W (n=238) groups, 9%, 9% and 7% had ≥1 SAE; 2%, 3% and 3% had ≥1 serious infection; 2 Q8W pts (fungal esophagitis, disseminated herpes zoster) and 1 PBO→Q4W pt (listeria meningitis) had opportunistic infections; 1 PBO→Q4W pt died (road traffic accident); 1 PBO-randomized pt had IBD; no pt had anaphylactic or serum sickness reaction, or active TB.Conclusion:In biologic-naïve PsA pts, GUS improvements in joint and skin symptoms, physical function, and low rates of radiographic progression persisted through 2 years. GUS safety in PsA through 2 years was comparable with safety at 6 months and 1 year, similar between Q4W and Q8W, and consistent with GUS safety in psoriasis.

Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis

ObjectiveThe efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA).MethodsA systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs).ResultsTwenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks.ConclusionsIn this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Efficacy and safety of sirukumab in Japanese patients with moderate to severe rheumatoid arthritis inadequately controlled by disease modifying anti-rheumatic drugs: Subgroup analysis of a phase 3 study

Objective: To evaluate the efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis (RA) uncontrolled by disease-modifying antirheumatic drugs.Methods: This subgroup analysis based on a double-blind, placebo-controlled, 52-week phase 3 study (SIRROUND-D) assessed American College of Rheumatology (ACR) 20 response at week 16 and van der Heijde-modified Sharp score (vdH-S) at week 52 (coprimary endpoints).Results: A total of 168 (Japanese)/1670 patients received sirukumab 50 mg/4 weeks (q4w, n = 58), 100 mg/every 2 weeks (q2w, n = 54), or placebo (n = 56) subcutaneously. Significantly more patients achieved ACR20 response at week 16 with sirukumab (50 mg q4w: 69.0%; 100mg q2w: 66.7%) vs. placebo (21.4%; p < .001). Median change from baseline in total vdH-S score at week 52 was significantly lower with sirukumab (50 mg q4w: 0.3, p = .024; 100 mg q2w: 0.0, p = .002) vs. placebo (1.3). Sirukumab consistently showed greater improvements in secondary endpoints at weeks 24 and 52. Nasopharyngitis, elevated liver enzymes, injection site erythema and upper respiratory tract infections were the common treatment-emergent adverse events (TEAEs). Incidences of TEAEs and serious AEs were consistent between sirukumab groups through week 52.Conclusion: Sirukumab showed clinically meaningful improvements consistent with significant improvements in the global study. No new safety signals were observed.

Clinical efficacy, radiographic, and safety results of golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior therapy with disease-modifying antirheumatic drugs: Final results of the GO-MONO trial through week 120

Objective: Evaluate the safety and efficacy of golimumab through week 120 in Japanese patients with active rheumatoid arthritis (RA) previously treated with DMARDs.Methods: Japanese patients with active RA despite prior DMARDs were randomized to placebo (Group 1, n = 105), golimumab 50 mg (Group 2, n = 101), or golimumab 100 mg (Group 3, n = 102). At week 16, Group 1 patients crossed over to golimumab 50mg; after week 52, a one-time golimumab dose reduction from 100 to 50 mg was permitted. Assessments included ACR20/50/70 responses and good/moderate DAS28-ESR responses. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Safety and efficacy were assessed through week 120.Results: ACR20 response rates at week 52 in Group 1, Group 2, and Group 3 were 70.6%, 71.4%, and 81.9%, respectively, and maintained through week 104 (87.2%, 85.1%, 88.9%, respectively) and week 120 (86.1%, 87.0%, 89.5%, respectively). Similar trends were observed for ACR50, ACR 70, and DAS28-ESR. Median change in total vdH-S at weeks 52, 104, and 120 ranged from 0.0 to 1.5 across treatment groups. Through week 120, 93.8%/97.1% had an AE with golimumab 50 mg/100 mg, respectively, and 19.7%/11.8% had an SAE. Infections were the most common AE.Conclusion: Clinical response to golimumab 50 mg and 100 mg was maintained over 2 years in Japanese patients with active RA despite prior DMARDs.

Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis

ObjectiveTo evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials.MethodsIn...

Predictive factors related to the efficacy of golimumab in patients with rheumatoid arthritis.

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metallo-proteinase (MMP)-3, TNF-α, and IL−6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

Greater body mass independently predicts less radiographic progression on X-ray and MRI over 1–2 years

IntroductionGreater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray...

AB0400 Intravenous Golimumab Inhibits Radiographic Progression and Maintains Clinical Efficacy and Safety in Patients with Active Rheumatoid Arthritis despite Methotrexate Therapy: 2-Year Results of A Phase 3 TRIAL of Intravenous Golimumab

ObjectivesTo evaluate long-term clinical/radiographic efficacy of IV GLM 2mg/kg+MTX in active RA despite MTX through wk112.Methods592 pts with active RA (≥6/66 SJC, ≥6/68 TJC, CRP≥1.0mg/dL, RF and/or anti-CCP positive) despite...

SP0065 What is the Target for Ra? “The Imaging Target”

The best imaging target for remission is demonstration that no progression of structural damage has occurred. Radiographs are able only to show inhibition of structural damage over a 6 to...

OP0080 Impact of Persistent Minimal Disease Activity on Long-Term Outcomes in Psoriatic Arthritis: Results from 5 Years of the Long Term Extension of A Randomized, Placebo-Controlled, Study

BackgroundAlthough criteria for Minimal Disease Activity (MDA) in psoriatic arthritis (PsA) have been developed and validated, a paucity of data concerning the impact of reaching MDA on long-term outcomes remains.ObjectivesWe...

OP0079 Ustekinumab is Effective in Inhibiting Radiographic Progression in Patients with Active Psoriatic Arthritis: Integrated Data Analysis of Two Phase 3, Randomized, Placebo-Controlled Studies

ObjectivesTo evaluate the effect of ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibition of progression of structural damage in patients with active psoriatic arthritis (PsA) at wk24 and wk52 in...

Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials

ObjectiveEvaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA).MethodsWe conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3,...

Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy: results up to 1 year of the phase 3, randomised, multicentre, double blind, placebo controlled GO-FURTHER trial

ObjectiveReport on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA).MethodsPatients (n=592) with active RA...

Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial

ObjectiveTo determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort.DesignThis study included 256 methotrexate (MTX)-naïve RA patients from a randomised...

AB0267 Five-year safety and efficacy of golimumab in patients with active rheumatoid arthritis despite prior treatment with methotrexate: final study results of the phase 3, randomized placebo-controlled go-forward trial

ObjectivesFinal 5yr safety and efficacy results of subcutaneous golimumab (GLM)+/-MTX in a phase 3 trial (GO-FORWARD) of pts with active rheumatoid arthritis (RA) despite MTX therapy are reported.MethodsPts were randomized...

FRI0176 Golimumab, a human anti-TNF monoclonal antibody, administered subcutaneously every four weeks as monotherapy in patients with active rheumatoid arthritis despite dmard therapy: 52-week results of clinical, radiographic and pharmacokinetic assessments

ObjectivesTo assess the efficacy and safety of golimumab (GLM) as monotherapy in Japanese patients (pts) with active rheumatoid arthritis (RA) despite DMARD therapy.MethodsGO-MONO is a multicenter, randomized, double-blind, placebo (PBO)-controlled...

SAT0486 Early MRI Measures Independently Predict 1- and 2- Year X-Ray Progression: Results from a Large Clinical Trial

ObjectivesEarly predictors of progression in structural joint damage in RA are lacking. We evaluated if early MRI measures of inflammation & erosion at baseline (BL), 12 & 24wks could predict...