Dataset Information

Efficacy and Safety of Intravenous Golimumab Through One Year in Patients With Active Psoriatic Arthritis.

ABSTRACT:

Objective

The present study was undertaken to evaluate the safety and efficacy of intravenous (IV) golimumab in patients with active psoriatic arthritis (PsA) through 1 year.

Methods

GO-VIBRANT was a phase III, randomized, placebo-controlled trial of 480 adults with active PsA. Patients were randomized to receive IV placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, and every 8 weeks, with placebo crossover to golimumab at weeks 24, 28, and every 8 weeks thereafter. Efficacy through week 52 was assessed using the American College of Rheumatology (ACR) ≥20%, 50%, or 70% improvement criteria (ACR20/50/70), and the Psoriasis Area and Severity Index ≥75% improvement criteria (PASI75). Radiographic progression was measured using the PsA-modified Sharp/van der Heijde score (SHS). Adverse events (AEs) were monitored through week 60.

Results

The primary and major secondary end points through week 24 were achieved. At week 52, 76.8% of patients in the golimumab group and 77.0% in the placebo-crossover group achieved an ACR20 response, 58.1% and 53.6%, respectively, achieved an ACR50 response, and 38.6% and 33.9%, respectively, achieved an ACR70 response. Among patients with ≥3% body surface area affected, 71.9% in the golimumab group and 60.6% in the placebo-crossover group achieved a PASI75 response at week 52. Mean change from baseline in total SHS at week 52 was -0.5 in the golimumab group and 0.8 in the placebo-crossover group. Through week 60, 50.9% of all golimumab-treated patients had ≥1 AE, and 5.2% had ≥1 serious AE. There were no opportunistic infections, 2 malignancies, and 1 death in patients treated with golimumab.

Conclusion

Sustained improvements in joint and skin disease in patients with PsA were maintained through 1 year in the GO-VIBRANT study. No new safety signals for IV golimumab were identified.

SUBMITTER: Husni ME

PROVIDER: S-EPMC7318581 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Efficacy and Safety of Intravenous Golimumab Through One Year in Patients With Active Psoriatic Arthritis.

Husni M Elaine ME Kavanaugh Arthur A Murphy Frederick F Rekalov Dmytro D Harrison Diane D DD Kim Lilianne L Lo Kim Hung KH Leu Jocelyn H JH Hsia Elizabeth C EC

Arthritis care & research 20200515 6

<h4>Objective</h4>The present study was undertaken to evaluate the safety and efficacy of intravenous (IV) golimumab in patients with active psoriatic arthritis (PsA) through 1 year.<h4>Methods</h4>GO-VIBRANT was a phase III, randomized, placebo-controlled trial of 480 adults with active PsA. Patients were randomized to receive IV placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, and every 8 weeks, with placebo crossover to golimumab at weeks 24, 28, and every 8 weeks thereafter. E ...[more]

PMID: 30980514

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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:ObjectiveGuselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings.MethodsAdults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized.ResultsOf 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumab-randomized patients. No patient developed an opportunistic infection or died.ConclusionIn biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.

Project description:ObjectivesThe safety and efficacy of subcutaneous golimumab through 2 years of maintenance therapy was evaluated in patients with moderate-to-severe ulcerative colitis (UC).MethodsPatients completing treatment through week 52 (placebo, golimumab 50, 100, every-4-weeks (q4w)) and evaluations at week 54 were eligible for this long-term extension (LTE) trial. Patients receiving placebo or golimumab 50 mg with worsening disease during the LTE could receive golimumab 100 mg. Efficacy assessments included the Mayo physician's global assessment (PGA) subscore, inflammatory bowel disease questionnaire (IBDQ), and corticosteroid use. Patients who were randomized to golimumab at PURSUIT-Maintenance baseline and continued receiving golimumab during the LTE were analyzed for efficacy (using intention-to-treat and "as observed" analyses; N=195) and safety (N=200). Patients treated with golimumab at any time from induction baseline through week 104 (N=1240) constituted the overall safety population.ResultsBaseline demographics and disease characteristics of patients entering the LTE receiving golimumab were similar to those of all patients randomized to golimumab maintenance at baseline. At week 104, 80.5% (157/195) of patients had a PGA=0/1 (range weeks 56-104: 80.5-91.8%) and 56.4% (110/195) had a PGA=0 (weeks 56-104: range: 53.8-58.5%). Through week 104, 86% of patients maintained inactive or mild disease activity. Among 174 corticosteroid-free patients at week 54, 88.5% remained corticosteroid-free at week 104. At week 104, 62.2% (120/193) had an IBDQ score ≥170. Tuberculosis, opportunistic infection, and malignancy rates were low, and the overall safety profile was similar to that reported through week 54. Two non-melanoma skin cancers, one metastatic colon cancer, and two deaths (biventricular heart dysfunction, sepsis) occurred between weeks 54 and 104.ConclusionSubcutaneous golimumab q4w through 2 years maintained clinical benefit and reduced corticosteroid use among patients who did well in the maintenance study. No new safety signals were observed.

Project description:ObjectiveTo evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged < 65 years and those ≥ 65 years who were enrolled in the GO-FURTHER study.MethodsIn the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, patients with active RA were randomized to intravenous (IV) golimumab 2 mg/kg + MTX or placebo + MTX at weeks 0 and 4, then every 8 weeks thereafter (with crossover to golimumab at week 16 [early escape] or week 24 [per-protocol]). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology (ACR) 20/50/70 response criteria. Efficacy and adverse events (AEs) were monitored through 2 years. Efficacy and AEs were summarized for patients aged < 65 years or ≥ 65 years; AEs were also summarized for patients < or ≥ 70 years and patients < or ≥ 75 years.ResultsIn GO-FURTHER, 592 patients were randomized to receive placebo (n = 197) or golimumab (n = 395), 515 were aged < 65 years and 77 were ≥ 65 years. At week 24, ACR20 response rates were greater for golimumab + MTX patients compared with placebo + MTX for patients < 65 years (61.6% vs 31.3%, p < 0.001) and those ≥ 65 years (69.5% vs 33.3%; p < 0.01). Infections were the most common AE through week 112 (51.6% in patients < 65 years; 55.3% in patients ≥ 65 years); upper respiratory infections were the most common infection in patients < 65 years (13.2%) and those ≥ 65 years (11.8%). Serious AEs occurred in 17.7% in patients < 65 years and 25.0% of patients ≥ 65 years and included malignancies, pneumonia, fractures, acute pancreatitis, cellulitis, and bacterial arthritis.ConclusionsIn GO-FURTHER, ACR response rates were similar between patients < 65 years and patients ≥ 65 years within each treatment group. AEs in elderly patients were similar to the known safety profile of IV golimumab. Immunosenescence is known to increase the risk of infections in the elderly. Elderly patients had a numerically higher incidence of serious infections. Six malignancies occurred in golimumab-treated patients, all in patients < 65 years.Trial registrationclinicaltrials.gov: NCT00973479 . Registered September 9, 2009.

Project description:ObjectivesTo 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.MethodsPharmacokinetic, 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).ResultsIn 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.ConclusionsThese 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 registrationGO-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.

Dataset Information

Efficacy and Safety of Intravenous Golimumab Through One Year in Patients With Active Psoriatic Arthritis.

Objective

Methods

Results

Conclusion

Publications

Efficacy and Safety of Intravenous Golimumab Through One Year in Patients With Active Psoriatic Arthritis.

Similar Datasets

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