BACKGROUND:

Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial.

OBJECTIVES:

To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities.

DATA SOURCES:

Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals.

REVIEW METHODS:

A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model.

RESULTS:

Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained.

LIMITATIONS:

The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review.

CONCLUSIONS:

Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC.

STUDY REGISTRATION:

This study is registered as PROSPERO CRD42013006883.

FUNDING:

The National Institute for Health Research Health Technology Assessment programme.

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OBJECTIVE:

</b>The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.<b>

METHODS:

</b>Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.<b>

RESULTS:

</b>The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.<b>

CONCLUSION:

</b>The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.

Objective. To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA). Methods. MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). Results. An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. Conclusion. Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns. © 2009, American College of Rheumatology.

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Background: Golimumab (GOL) is a tumor necrosis factor inhibitor that is used for various types of inflammatory arthritis such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This article is a systematic review of the evidence for the efficacy and safety of golimumab in inflammatory arthritides, specifically RA, PsA and AS. Methods: We conducted a search of randomized controlled trails in MEDLINE [PubMed], CENTRAL, Embase, and Current Controlled Trials databases (ClinicalTrials.gov) through 2017 for studies that evaluated golimumab in inflammatory arthritides. We focused on pivotal, phase III trials for this review of the safety and efficacy of the drug. However, as some important information is not available in detail in publications from the phase III studies, additional individual studies pertaining to antidrug antibodies were also included. Results: A total of 12, randomized, double-blind, placebo-controlled studies were included in this review of literature. Two trials focused on the GOL response in the PsA population, four trials focused on the GOL response in the AS population, and five trials focused on the GOL response in the RA population. Additional studies that evaluated autodrug antibodies produced in patients using GOL were also included. Conclusion: Golimumab was found to be clinically effective and also have a good safety profile in the treatment of RA, PsA, and AS based on data available from large studies.

BACKGROUND:

Golimumab (GOL) is a tumor necrosis factor inhibitor that is used for various types of inflammatory arthritis such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This article is a systematic review of the evidence for the efficacy and safety of golimumab in inflammatory arthritides, specifically RA, PsA and AS.

METHODS:

We conducted a search of randomized controlled trails in MEDLINE [PubMed], CENTRAL, Embase, and Current Controlled Trials databases (ClinicalTrials.gov) through 2017 for studies that evaluated golimumab in inflammatory arthritides. We focused on pivotal, phase III trials for this review of the safety and efficacy of the drug. However, as some important information is not available in detail in publications from the phase III studies, additional individual studies pertaining to antidrug antibodies were also included.

RESULTS:

A total of 12, randomized, double-blind, placebo-controlled studies were included in this review of literature. Two trials focused on the GOL response in the PsA population, four trials focused on the GOL response in the AS population, and five trials focused on the GOL response in the RA population. Additional studies that evaluated autodrug antibodies produced in patients using GOL were also included.

CONCLUSION:

Golimumab was found to be clinically effective and also have a good safety profile in the treatment of RA, PsA, and AS based on data available from large studies.

Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned to receive a single infusion of placebo or golimumab (0.1, 0.3, 1, 3, 6, or 10 mg/kg). Serum concentrations of golimumab were determined using a validated enzyme-linked immunosorbent assay method. In addition to the noncompartmental analysis and compartmental modeling, a population pharmacokinetics analysis using NONMEM was also conducted. Both the maximum serum concentration and the area under the serum concentrationtime curve appeared to increase in a dose-proportional manner. The median half-life ranged from 7 to 20 days. A 2-compartment population pharmacokinetic model adequately described the pharmacokinetics of golimumab. The following pharmacokinetic parameters (typical value [% coefficient of variation]) were estimated from the population pharmacokinetic model: clearance (CL= 0.40 [10.1%] L/d), volume of distribution in the central compartment (V(c): 3.07 [6.4%] L), intercompartmental clearance (Q: 0.42 [15.5%] L/d), and volume of distribution in the peripheral compartment (V(p): 3.68 [11.8%] L). Interindividual variability of the pharmacokinetic parameters was quantified for CL (44.3%), V(c) (25.5%), Q (44.6%), and V(p) (44.6%). Residual variability was estimated to be 15.0%. Body weight was found to be an important covariate on V(c). Golimumab was generally well tolerated. The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study.

Intravenous golimumab in a dosage of 2 mg/kg, initially given every 4 weeks but then every 8 weeks, in addition to methotrexate, is effective in the treatment of patients with rheumatoid arthritis. This weight-based infusion is administered over thirty minutes with an acceptable safety profile. Since it is a relatively new formulation, more time will be required to assess its specific role in the rheumatologists' armamentarium and to appreciate more fully its long-term safety.

Objectives: Immune-mediated rheumatic disease (IMRD) including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are severe and disabling chronic diseases in rheumatology. Bioogics such as subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) have transformed the management of the diseases. The study objective was to describe treatment persistence in a real-world setting, among patients diagnosed with IMRD, initiating treatment with golimumab (GLM) in France. Methods: The Système National d'Information Inter-régime [French national health insurance scheme information-sharing system] database lists all outpatient and inpatient healthcare consumption for individuals covered by the general health insurance scheme. Patients with RA, PsA or AS were included through Long Term Disease (LTD) status and hospital admission, based on ICD-10 codes. Then, patients were then identified through filled prescription of GLM between 06/01/2012 and 12/31/2013. A sensitivity analysis was conducted on patients with no subcutaneous or intravenous biotherapy before initiating GLM. Persistence was estimated using Kaplan Meier analysis at 12 and 24 months. Results: A total of 1,315 patients initiating GLM with RA were identified, 2,656 with AS and 514 with PsA. For all IMRD patients (bionaïves or not) 12 months persistence rate was 54.7%. 12 month persistence rate was 56.6% for RA, 54.5% for AS and 50.8% for PsA. 24 month persistence rates were 40.1%, 41.0% and 35.0% for RA, AS and PsA, respectively. For all IMRD patients GLM persistence rates was 60.2% at 12 months and 47 % at 24 months. Persistence rate at 12 months was 63.8% in RA, 58.9% in AS and 55.9% in PsA; and 48.5% at 24 months in RA, and 44.1% in AS, and 57.1% in PsA. Conclusions: GLM persistence rates at 12 months are between 55% (bionaïve and bioswitch patients) and 60% (bionaïve patients only). Those results confirm persistence rates published in the literature at 12 months for naïve patients.