Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Deodhar A

PROVIDER: S-EPMC10326229 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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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.

Deodhar Atul A Shiff Natalie J NJ Gong Cinty C Chan Eric K H EKH Hsia Elizabeth C EC Lo Kim Hung KH Akawung Alianu A Kim Lilianne L Xu Stephen S Reveille John D JD

Rheumatology and therapy 20230615 4

<h4>Introduction</h4>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.<h4>Methods</h4>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 Spondy ...[more]

PMID: 37322274

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Project description:ObjectiveTo compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS).MethodsPropensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4-52.ResultsBefore matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28-44 (e.g., OR = 9.05 [95% CI 1.62-50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses.ConclusionsThis is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up. Key Points • Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial. • Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials. • Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP. • This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

Project description:BackgroundIntravenous (IV) golimumab, a TNFi, is approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We analyzed pooled safety results from three phase 3 IV golimumab trials in these rheumatologic diseases and hypothesized that the safety profile of IV golimumab would be similar to that established for other TNFi, including subcutaneous golimumab.MethodsData from three double-blind, randomized trials of IV golimumab in patients with RA, PsA, and AS, each with a placebo-controlled period and an extension of active treatment, were included. Golimumab 2 mg/kg was administered at weeks 0 and 4, then every 8 weeks through week 100 (RA) or week 52 (PsA, AS). Concomitant low-dose, oral corticosteroids were permitted. Concomitant methotrexate was required in the RA trial and permitted in the PsA and AS trials; placebo patients crossed over to golimumab at weeks 24 (RA, PsA) and 16 (AS), respectively. Adverse events (AEs), including infections, serious infections, malignancies, and major adverse cardiovascular events (MACE), were assessed through week 112 (RA) or week 60 (PsA, AS).ResultsIn total, 539 patients were randomized to placebo, and 740 patients were randomized to golimumab; 1248 patients received ≥ 1 golimumab administration. Among the placebo and golimumab patients, respectively, during the placebo-controlled periods, 40.6% and 50.3% had an AE, 2.4% and 3.8% had a serious AE, and 0.4% and 0.8% had a serious infection. Among all golimumab-treated patients, the numbers of events/100 patient-years (95% CI) were as follows: AEs, 175.2 (169.0, 181.6); serious AEs, 12.7 (11.0, 14.5); serious infections, 3.4 (2.5, 4.4); active tuberculosis, 0.4 (0.1, 0.8); opportunistic infection, 0.2 (0.1, 0.6); malignancies, 0.4 (0.2, 0.9), and MACE, 0.5 (0.2, 1.0). There were no cases of lymphoma. Three (0.6%) placebo-treated patients and 6 (0.5%) golimumab-treated patients died during the studies. Concomitant methotrexate was associated with increased occurrence of elevated alanine transaminase levels and lower incidence of antibodies to golimumab. During the placebo-controlled periods, serious infections in the placebo and golimumab groups were more common in patients receiving concomitant low-dose oral corticosteroids vs. those not receiving corticosteroids.ConclusionsIV golimumab demonstrated a safety profile that was broadly consistent across these rheumatologic indications and with other TNFi, including subcutaneous golimumab. Concomitant methotrexate or corticosteroids were associated with an increase in specific AEs.Trial registrationsClinicalTrials.gov , NCT00973479 . Registered on September 9, 2009.Clinicaltrialsgov , NCT02181673 . Registered on July 4, 2014.Clinicaltrialsgov , NCT02186873 . Registered on July 10, 2014.

Project description:BackgroundIn the present study, we evaluated relationships between serum biomarkers and clinical/magnetic resonance imaging (MRI) findings in golimumab-treated patients with ankylosing spondylitis.MethodsIn the GO-RAISE study, 356 patients with ankylosing spondylitis randomly received either placebo (n = 78) or golimumab 50 mg or 100 mg (n = 278) injections every 4 weeks through week 24 (placebo-controlled); patients continuing GO-RAISE received golimumab through week 252. Up to 139/125 patients had sera collected for biomarkers/serial spine MRI scans (sagittal plane, 1.5-T scanner). Two blinded readers employed modified ankylosing spondylitis spine magnetic resonance imaging score for activity (ASspiMRI-a) and ankylosing spondylitis spine magnetic resonance imaging score for chronicity. Spearman correlations (r s) were assessed between serum biomarkers (n = 73) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive-protein (CRP)-based Ankylosing Spondylitis Disease Activity Score (ASDAS), modified Stokes Ankylosing Spondylitis Spine Score (mSASSS), and ASspiMRI scores. Serum biomarkers predicting postbaseline spinal fatty lesion development and inflammation were analyzed by logistic regression.ResultsSignificant, moderately strong correlations were observed between baseline inflammatory markers interleukin (IL)-6, intracellular adhesion molecule-1, complement component 3 (C3), CRP, haptoglobin, and serum amyloid-P and baseline ASDAS (r s = 0.39-0.66, p ≤ 0.01). Only baseline leptin significantly correlated with ASDAS improvement at week 104 (r s = 0.55, p = 0.040), and only baseline IL-6 significantly predicted mSASSS week 104 change (β = 0.236, SE = 0.073, p = 0.002, model R 2 = 0.093). By logistic regression, baseline leptin, C3, and tissue inhibitor of metalloproteinase (TIMP)-1 correlated with new fatty lesions per spinal MRI at week 14 and week 104 (both p < 0.01). Changes in serum C3 levels at week 4 (r s = 0.55, p = 0.001) and week 14 (r s = 0.49, p = 0.040) significantly correlated with BASDAI improvement at week 14. Baseline IL-6 and TIMP-1 (r s = -0.63, -0.67; p < 0.05) and reductions at week 4 in IL-6 (r s = 0.61, p < 0.05) and C3 (r s = 0.72; p < 0.05) significantly correlated with week 14 ASspiMRI-a improvement.ConclusionsExtensive serum biomarker multiparametric analyses in golimumab-treated patients with ankylosing spondylitis demonstrated few correlations with disease activity or MRI changes; IL-6 weakly correlated with radiographic progression.Trial registrationClinicalTrials.gov identifier: NCT00265083 . Registered on 12 December 2005.

Project description:ObjectiveThe Non Interventional Evaluation with Golumimab (GO-NICE) study aimed to document patient and treatment characteristics as well as clinical effectiveness and safety in adult patients newly treated with the tumour necrosis factor inhibitor golimumab (GLM).DesignProspective non-interventional study with 24-month observation per patient.Setting158 office-based and clinical-based physicians in Germany.InterventionGLM administered in the 50 mg dose subcutaneously in monthly intervals under real-life conditions.ResultsOf the 1613 included patients, 1458 patients were eligible for final analysis: 474 patients with rheumatoid arthritis (RA, 54.9±13.4 years, 72.8% women, 64.7% biologic-naïve), 501 with psoriatic arthritis (PsA, 50.5±12.1 years, 54.1% women, 56.5% biologic-naïve) and 483 with ankylosing spondylitis (AS, 43.6±12.3 years, 66.5% men, 61.0% biologic-naïve). 664 patients completed follow-up (2-year retention rate 45.5%). Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28-ESR) decreased from 5.0 to 2.9 after 24 months (p<0.0001) in patients with RA, and Bath Ankylosing Spondylitis Disease Index score decreased from 5.1 to 2.4 (p<0.0001) in patients with AS. Response rate calculated in patients with PsA by modified Psoriatic Arthritis Response Criteria was 67.9% after 24 months. Most adverse events were of mild or moderate nature, and no new safety signals were detected. According to the physicians' clinical assessments, treatment with GLM was successful (no adverse drug reaction and a clear or moderate therapeutic effect in an individual patient) in 55.0%-56.6% of patients with RA, PsA and AS, respectively, at month 3, increasing from 74.5% to 76.1% at month 24.ConclusionsGLM subcutaneously once monthly led to substantial improvements in clinical effectiveness in patients with various inflammatory rheumatic diseases who could be followed up in a real-life setting in Germany. The treatment was well tolerated, and the safety profile of GLM was consistent with that observed in the previous randomised controlled trials.Trial registration numberNCT01313858.

Project description:Introduction/objectivesTo evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).MethodsPatients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.ResultsAt Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (-2.91 vs -0.71), and WLQ productivity loss score (-2.92 vs -0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: -2.89 and -3.31; WLQ productivity loss: -4.49 and -3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.ConclusionIV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability. Key Points • In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes • IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity.

Dataset Information

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

Methods

Results

Conclusions

Trial registration

Publications

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.

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