Intravenous Golimumab Research Articles

Comparative analysis of US real-world dosing patterns and direct infusion-related costs for matched cohorts of rheumatoid arthritis patients treated with infliximab or intravenous golimumab.

PurposeThe objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.MethodsAdult RA patients with a new episode of GLM-IV or IFX treatment between Janu-ary 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index methotrexate use. Paid amounts for drugs and associated administration costs were applied to treatment group dosing patterns.ResultsFinal matched treatment groups included 547 GLM-IV and 547 IFX patients (mean age = 55–56 years). Mean (SD) follow-up was 609 (161) days for GLM-IV and 613 (163) days for IFX. Treatment duration was 396 (240) days for GLM-IV and 397 (239) days for IFX. Overall, 80% of GLM-IV and 39% of IFX maintenance infusions were given approximately every 8 weeks; and 6% of GLM-IV and 53% of IFX maintenance infusions occurred more frequently than every 8 weeks (P<0.001). When weighting of the maintenance infusion interval was applied, the mean number of induction plus maintenance infusions during the first year of treatment was estimated at 7.03 for GLM-IV and 9.48 for IFX. From the commercial perspective, drug plus administration costs per infusion were $5,846 for GLM-IV and $5,444 for IFX with total annual cost of therapy for GLM-IV patients costing $10,507 less than that for IFX patients in the first year and $6,774 less than that for IFX patients in subsequent years.ConclusionAnnual GLM-IV drug plus administration costs for commercial health plans were significantly less than IFX in RA patients due to differences in real-world dosing and administration.

PMS78 - CHANGES IN THE PRICES OF INCUMBENT TNF-ALPHA INHIBITORS FOLLOWING THE MARKET ENTRY OF COMPETITORS

Before 2009, etanercept, infliximab and adalimumab were the only tumor necrosis factor alpha (TNF-alpha) inhibitors approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis (RA). Since then, three new therapies have been approved for this indication, including: subcutaneous golimumab in April 2009, certolizumab pegol in May 2009, and intravenous golimumab in July 2013. The objective of this study was to assess how prices of incumbent TNF-alpha inhibitors changed in response to the market entry of new agents. We obtained 2005-2017 monthly wholesale acquisition costs for all TNF-alpha inhibitors approved for RA from Analysource. For each month between January 2005 and January 2017, we calculated the annual cost of treating a standard 80kg/1.80m patient with each drug. We constructed an interrupted time-series analysis with a linear model to test how the entry of new agents affected trends in prices of incumbent products. The linear model regressed the annual cost of treatment against a continuous variable for month, two indicator variables for each period after new drug entry (one for April 2009-July 2013, another for July 2013-end of the study period), and the interactions between each indicator variable and the time variable. After the entry of subcutaneous golimumab and certolizumab pegol, the annual cost of treatment increased a 284% faster, from US$69 every month between January 2005 and April 2009 to US$196 every month between April 2009 and July 2013 (p-value for trend change<0.001). After the entry of intravenous golimumab, the annual cost of treatment increased by US$488 every month between July 2013 and January 2017 (p-value for trend change<0.001), a 249% faster than during the previous period. Although increased competition should theoretically drive prices down, we found that prices of incumbent TNF-alpha inhibitors significantly increased following the entry of new competitors.

The Effectiveness of Intravenous Golimumab Administered Directly After Infliximab in Rheumatoid Arthritis Patients.

PurposeFor patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF.MethodsPatient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy.FindingsSignificant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p < 0.05). Limited changes were observed through the RAPID3 and PtGA.ConclusionsFindings from this study indicate that intravenous golimumab is effective in managing RA in a population of patients switching directly from infliximab (mean last dose 7.4 mg/kg).

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab

Objectives: To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction.Methods: An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher’s exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction.Results: One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time.Limitations: Findings may not be representative of care delivery for all RA infusion practices or RA patients.Conclusions: Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Safety and Efficacy of Golimumab Administered Intravenously in Adults with Ankylosing Spondylitis: Results through Week 28 of the GO-ALIVE Study.

To evaluate the safety and efficacy of intravenous golimumab (GOL) in patients with active ankylosing spondylitis (AS). In a phase III, randomized, double-blind, placebo (PBO)-controlled trial, 208 patients were randomized (1:1) to intravenous (IV) infusions of GOL 2 mg/kg (n = 105) at weeks 0, 4, 12, and every 8 weeks, or PBO (n = 103) at weeks 0, 4, and 12, with crossover to GOL at Week 16. The primary endpoint was ≥ 20% improvement from baseline in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) at Week 16. Secondary endpoints included ASAS40, ≥ 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), and change in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16. Safety was monitored through Week 28. Significantly greater proportions of GOL-treated patients had ASAS20 response at Week 2 (37.1% vs 19.4%; p = 0.005) and at Week 16 (73.3% vs 26.2%; p < 0.001). At Week 16, 41.0% of those receiving GOL achieved BASDAI50 compared with 14.6% of those taking PBO (p < 0.001), and the GOL group had greater mean improvement in BASFI (-2.4 vs -0.5; p < 0.001). Through Week 16, 23.3% of patients in the PBO group and 32.4% of patients in the GOL group had ≥ 1 adverse event (AE); infections being the commonest type of AE. Through Week 28, two GOL-treated patients had a serious AE. GOL 2 mg/kg administered IV at weeks 0, 4, and every 8 weeks significantly reduced the signs and symptoms of AS in adults. AE were consistent with other antitumor necrosis factor therapies, with no new safety signals (Clinicaltrials.gov: NCT02186873).

Clinical trials: Intravenous golimumab effective for PsA.

Clinical trials: Intravenous golimumab effective for PsA.

Clinical response to golimumab in rheumatoid arthritis patients who were receiving etanercept or adalimumab: results of a multicenter active treatment study

Objective: Evaluate the efficacy and safety of subcutaneous (SC) golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite etanercept + MTX or adalimumab + MTX therapy and evaluate whether intravenous (IV) golimumab could rescue patients who were nonresponders to SC golimumab.Methods: In this multicenter, assessor-blinded, active-switch study of patients with RA (n = 433) with inadequate response to etanercept or adalimumab + MTX, patients continued MTX and received open-label SC golimumab 50 mg every 4 weeks through week 12. DAS28-ESR good responders at week 16 continued open-label SC golimumab through week 52 (Group 1); nonresponders were randomized to double-blind golimumab SC 50 mg (Group 2-SC) or IV 2 mg/kg (Group 2-IV). Week 14 ACR20 was the primary endpoint; assessments continued through week 52 and for patients in the voluntary long-term extension through week 76. A major secondary endpoint was the proportions of patients with ACR20 response at week 52 relative to week 16 in Group 2-SC and Group 2-IV.Results: At week 14, 34.9% (p < 0.001) achieved an ACR20. At week 52, patients in Group 1 (n = 75) achieved an ACR20 (62.7%). In Groups 2-SC (n = 91) and 2-IV (n = 184), 13.2% and 9.2% had an ACR20 at week 52 relative to week 16, with no significant difference between the randomized groups; 42.9% and 47.8% achieved DAS28-ESR response relative to week 0. Through week 16, 4.6% of patients had a serious adverse event. No differences in the rates or types of adverse events were observed between SC and IV golimumab from weeks 16 to 52. The trial limitations included a higher than expected discontinuation rate as a result of a programming error.Conclusion: SC golimumab + MTX significantly suppressed disease activity in RA patients with inadequate response to etanercept and/or adalimumab + MTX. Patients randomized to Groups 2-SC and 2-IV had lower response rates than Group 1, with no difference between SC or IV mode of administration. The safety profile with IV golimumab was comparable to that established with SC golimumab.Trial registration: NCT01004432, EudraCT 2009-010582-23.

Prescribing Patterns of Intravenous Golimumab for Rheumatoid Arthritis

PurposeThe use of intravenous golimumab (GLM-IV), in combination with methotrexate, was approved by the US Food and Drug Administration in July 2013 for the treatment of moderate to severe, active rheumatoid arthritis (RA). GLM-IV is available in 50-mg vials, and the prescribing information specifies a dosing regimen of 2 mg/kg at 0 and 4 weeks and then every 8 weeks thereafter. The purpose of this study was to examine the patterns of prescribing and administration of GLM-IV, including the demographic, clinical, and utilization characteristics of patients with RA newly treated with GLM-IV. MethodsRheumatology practices across the continental United States were solicited for a chart-review study. Inclusion criteria were: (1) diagnosis of RA; (2) current treatment with GLM-IV; (3) age ≥18 years; and (4) lack of pregnancy (in female patients). Physicians were offered a monetary incentive for each eligible chart provided. An electronic case-report form was developed to aid in the chart data extraction and included fields for demographic characteristics, available comorbid diagnoses, prior RA treatments, and doses and dates of GLM-IV administration. FindingsA total of 117 eligible patient charts from 15 rheumatologist practices were reviewed. The patient sample was predominantly female (81.2%), with a mean (SD) age of 55.4 (14.5) years. A total of 55.6% of patients had evidence of biologic treatment before receiving GLM-IV, and 53% had at least 1 comorbid condition. In total, 300 individual GLM-IV infusions from this sample were reviewed. Due to the relatively recent approval of GLM-IV use by the US Food and Drug Administration, the majority of patients in this sample (69.2%) had received only between 2 and 4 infusions at the time of the review. For infusion records with valid dose data, the mean number of administered vials was 3.6 (0.8) (total dose, 180 mg); the majority of patients received a dose consistent with the prescribed dose of 2 mg/kg. Combination therapy with methotrexate was observed in the charts of a minority of patients (27.4%). The mean interval between induction and the first follow-up infusion was 32.9 (11.4) days, with a mean maintenance interval of 56.5 (13.3) days. ImplicationsThis analysis provides an early glimpse of the patterns of prescribing GLM-IV. Overall, patients appeared to have been receiving GLM-IV in accordance with Food and Drug Administration labeling; although the rate of prescribing methotrexate was low, dosages and administration intervals were within the expected ranges.

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...

FRI0266 Health-Related Quality of Life of Patients with Rheumatoid Arthritis Achieving DAS28 Remission, Improvement in Physical Function and NO Radiographic Progression after Treatment with Intravenous Golimumab

ObjectivesTo evaluate “comprehensive remission” in patients with rheumatoid arthritis (RA) treated with intravenously administered golimumab (GLM) and the association with normalized health related quality of life (HRQOL).MethodsGO-FURTHER was a multicenter,...

FRI0038 Pharmacodynamic Effect of Intravenous Golimumab by Messenger RNA Expression Profiling

BackgroundRheumatoid Arthritis (RA) is a chronic systemic autoimmune disease resulting in joint inflammation and damage. Despite the current therapies available, only a small percentage of RA pts achieve remission. To...

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...

Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs: results of the GO-MORE study

ObjectivesTo evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus...

AB0269 Importance of steady-state trough concentrations after intravenous golimumab with concomitant methotrexate in patients with active rheumatoid arthritis

ObjectivesTo determine an optimized dosing regimen for IV golimumab in patients with active RA using population pharmacokinetic (PK) modeling and simulation.MethodsTwo Phase 3 trials were performed for IV golimumab. In...

THU0218 Intravenous Golimumab Inhibits Radiographic Progression and Maintains Clinical Efficacy and Safety in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: 1-Year Results of a Phase 3 Trial

ObjectivesEvaluate long-term efficacy of IV GLM 2mg/kg+MTX in active RAdespite MTX thru wk52.MethodsPts(n=592)with active RA(≥6/66 SJ,≥6/68TJ, CRP≥1.0mg/dL, RF&/or anti-CCP+at screen)despite ≥3mo of MTX(15-25mg/wk)participated. Pts rand to IV GLM2mg/kgorPBO at wks0&4...

FRI0169 Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with results observed by 2 weeks: Results of the phase 3, multicenter, double-blind, placebo-controlled trial

ObjectivesTo evaluate the efficacy of IV GLM 2mg/kg+MTX in pts with active RA despite MTX.MethodsPts (n=592) with active RA (≥6/66 swollen joints, ≥6/68 tender joints, CRP≥1.0mg/dL, rheumatoid factor and/or anti-CCP...

Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial

To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.v. infusion, on markers of inflammation in patients with RA. In this phase 1, open-label study, patients with active RA were randomized to receive s.c. golimumab 100 mg at baseline and every 4 weeks through week 20 (n = 33; group 1) or i.v. golimumab 2 mg/kg at baseline and week 12 (n = 16; group 2). Serum levels of CRP, IL-6, serum amyloid A (SAA), TNF receptor II (TNFRII), MMP-3, hyaluronic acid, haptoglobin, ferritin and haemoglobin and serum/urine hepcidin were measured at various time points. Associations between the biomarkers were assessed with Spearman's correlations. In both groups 1 and 2, decreases in mean serum levels of CRP, IL-6, SAA, TNFRII, MMP-3, haptoglobin, ferritin and hepcidin, and mean urine levels of hepcidin occurred within 1 week and were sustained through week 8. Decreases in concentrations of serum CRP, IL-6, SAA, MMP-3, hepcidin, ferritin and haptoglobin and urine hepcidin were maintained through week 24 in group 1, but began to reverse after week 8 in group 2. Among all patients, decreases in serum hepcidin correlated significantly with decreases in serum CRP and ferritin. Decreases in serum and urine concentrations of markers of inflammation occurred as early as 24 h after treatment with golimumab, and most of these improvements were sustained through week 24 in group 1.

GO-FURTHER with intravenous golimumab for active RA

GO-FURTHER with intravenous golimumab for active RA

Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial

ObjectivesEvaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate (MTX) in patients with active rheumatoid arthritis (RA) receiving MTX.MethodsPatients (n=592) with active disease (≥6/66 swollen, ≥6/68 tender joints, C-reactive protein ≥1.0...

Maintenance of Efficacy and Safety with Subcutaneous Golimumab Among Patients with Active Rheumatoid Arthritis Who Previously Received Intravenous Golimumab

To evaluate the efficacy/safety of subcutaneous (SC) golimumab in patients with rheumatoid arthritis (RA) who previously received intravenous (IV) golimumab with or without methotrexate (MTX). Adult patients with RA (n = 643) with persistent disease despite MTX (≥ 15 mg/wk for ≥ 3 months) were randomized to IV placebo + MTX (n = 129) or IV golimumab 2-4 mg/kg (± MTX) every 12 weeks (n = 514). Patients who completed the study through Week 48 could participate in the longterm extension (LTE), comprising open-label golimumab 50 mg SC every 4 weeks (± MTX) for 24 weeks (LTE-0 to LTE-24) followed by 16 weeks of safety followup (LTE-24 to LTE-40; MTX could be adjusted). At Week 48, 28% (nominal p < 0.001 vs placebo), 11%, and 8% of patients who received IV golimumab + MTX, golimumab alone, and placebo + MTX, respectively, achieved ≥ 50% improvement in the American College of Rheumatology response criteria (ACR50). Among the 505 patients who entered the LTE and were still participating, the proportion of patients treated with golimumab 50 mg SC (± MTX) achieving an ACR50 response increased to 44% at both LTE-14 and LTE-24. ACR20, ACR70, and 28-joint Disease Activity Score using C-reactive protein exhibited similar response patterns as ACR50. Infections were the most commonly reported adverse events through the end of IV golimumab dosing (37% placebo + MTX, 45% golimumab, 51% golimumab + MTX) and with SC golimumab from LTE-0 through LTE-40 (35% golimumab, 36% golimumab + MTX). Concomitant MTX use yielded lower incidences of antibodies to SC golimumab and injection-related reactions. Clinical improvements observed in golimumab-treated patients were sustained or improved in patients switched from IV (2-4 mg/kg ± MTX) to open-label SC (50 mg ± MTX) golimumab. Both IV and SC golimumab demonstrated acceptable safety profiles (Clinicaltrials.gov NCT00361335).