[Show abstract][Hide abstract] ABSTRACT: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis.
We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12.
A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%).
Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).
New England Journal of Medicine 03/2012; 366(13):1181-9. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiple trials demonstrate the tolerability and safety of etanercept. However, there are limited data on etanercept tolerability in large populations of patients with psoriasis or with extended therapy.
We sought to determine whether there is an increased safety risk associated with higher etanercept doses or with extended exposure in patients with psoriasis.
Integrated adverse event (AE) data from etanercept psoriasis trials were used to evaluate short-term (up to 12 weeks from controlled studies) and long-term (up to 144 weeks from uncontrolled extension studies) safety of etanercept (25 mg once weekly to 50 mg twice weekly). Long-term data were stratified by treatment regimens. Rates of noninfectious and infectious AE and standardized incidence ratios for malignancies were determined.
In short-term analyses, rates of noninfectious and infectious AE and serious noninfectious and infectious AE were comparable between placebo and etanercept groups. In both short- and long-term analyses, there were no dose-related increases in these events. Cumulative event rates for serious infections were not significantly different across dose groups and over time. The standardized incidence ratios for malignancies excluding nonmelanoma skin cancers did not achieve statistical significance. There was no increase in overall malignancies with etanercept therapy compared with the psoriasis population. Lymphoma (n = 2 patients), demyelination (n = 2), congestive heart failure (n = 7), and opportunistic infection (n = 1) were rare.
Study limitations include the rarity of some events and the resultant broad 95% confidence intervals.
In this integrated analysis, etanercept was well tolerated, and there were no signs of dose-related or cumulative toxicity over time.
Journal of the American Academy of Dermatology 10/2011; 67(2):245-56. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Health-related quality of life (HRQOL) is an important indicator of the burden of illness in moderate-to-severe plaque psoriasis. This study evaluated self-reported generic HRQOL among pediatric patients with moderate-to-severe plaque psoriasis based on pooled baseline clinical trial data and compared them to four common chronic diseases and to a healthy sample. The Pediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) Generic Core Scales was administered to 208 patients ages 4 to 17 years with stable, moderate-to-severe plaque psoriasis. Patients with moderate-to-severe plaque psoriasis were compared using one-sample t-tests to published PedsQL™ ( http://www.pedsql.org ) data on healthy children and pediatric patients with arthritis, psychiatric disorders, asthma, and diabetes. Pediatric patients with moderate-to-severe plaque psoriasis demonstrated significantly impaired physical, emotional, social, and school functioning in comparison to healthy children. The PedsQL™ Emotional and School Functioning Scales demonstrated the largest mean difference between the two groups (12.1, 11.1 points, respectively). In general, patients with plaque psoriasis demonstrated significantly more impaired generic HRQOL compared to patients with diabetes, comparable HRQOL to arthritis and asthma, and better HRQOL than psychiatric patients. In conclusion, the findings indicate that pediatric patients with moderate-to-severe plaque psoriasis have significantly impaired generic HRQOL in comparison to healthy children, and HRQOL generally comparable to other serious chronic diseases. These results demonstrate the significant negative impact of plaque psoriasis on the daily lives of these children from the patients' perspective.
European Journal of Pediatrics 09/2011; 171(3):485-92. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the threshold in disease activity associated with switching biologic treatment regimens in rheumatoid arthritis (RA) patients in real-world clinical practice.
Using data from a prospective observational North American cohort of RA patients through December 30, 2009, patients who initiated a new anti-tumor necrosis factor α (anti-TNFα) agent with ≥6 months of followup were identified. Patients were classified as switchers or maintainers depending on whether they continued their anti-TNF treatment or switched (including discontinuation) within 12 months. Level of disease activity measured by the Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints (DAS28) at the time of the switch (corresponding followup visit for maintainers) was examined and random-effect multivariable logistic regression was used to adjust for covariates.
Mean age and RA duration among 1,549 eligible patients were 56.1 and 9.6 years, respectively, 80% were women, 62% were initiating their first biologic, and 30% were initiating their second biologic. At the time of the switch, the median DAS28 and CDAI score were 3.1 and 8.4 among maintainers and 4.0 and 15.2 among switchers, respectively. Maintainers also experienced a greater amount of reduction in disease activity compared with switchers (CDAI: -7.7 versus -2.3, DAS28: -1.1 versus -0.3). The threshold to switch decreased over calendar time, with the greatest amount of reduction observed among patients with moderate disease activity.
On average, physicians and patients were willing to continue biologic treatment for patients who were at or near low disease activity. The threshold to switch decreased over time, especially among partial responders.
Arthritis care & research. 09/2011; 63(12):1672-9.
[Show abstract][Hide abstract] ABSTRACT: To evaluate persistence with anti-tumor necrosis factor (TNF) therapy and predictors of discontinuation in patients with rheumatoid arthritis (RA).
This retrospective analysis used data from RADIUS 1, a 5-year observational registry of patients with RA, to determine time to first- and second-course discontinuation of etanercept, infliximab, and adalimumab. First-course therapy was defined as first exposure to anti-TNF therapy, and second-course therapy was defined as exposure to anti-TNF therapy after the first discontinuation. Kaplan-Meier survival analysis was used to assess persistence, log-rank tests were used to compare therapies, and Cox proportional hazards models were used to assess potential predictors of treatment discontinuation.
This analysis included 2418 patients. Mean persistence rates were similar among treatments [first-course: etanercept, 51%; infliximab, 48%; adalimumab, 48% (followup was 54 weeks for etanercept and infliximab and 42 weeks for adalimumab); second-course: 56%, 50%, 46%, respectively (followup was 36 weeks for etanercept and infliximab and 30 weeks for adalimumab)]. Discontinuations of first-course therapy due to ineffectiveness were similar among treatments (etanercept, 19%; infliximab, 19%; adalimumab, 20%) and discontinuations due to adverse events were significantly (p = 0.0006) lower for etanercept than for infliximab (etanercept, 14%; infliximab, 22%; adalimumab, 17%). Predictors from univariable analysis of first- or second-course therapy discontinuation included increased comorbidities (etanercept), female sex (infliximab), Clinical Disease Activity Index > 22 (infliximab), and a Stanford Health Assessment Questionnaire score > 0.5 (adalimumab).
In this population, first- and second-course persistence was similar among anti-TNF therapies. First-course discontinuation due to adverse events was lower with etanercept compared with infliximab.
The Journal of Rheumatology 05/2011; 38(7):1273-81. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications.
Forty-nine U.S. and non-U.S. trials of etanercept, involving up to 13,977 patients for approved indications, with final trial reports as of May 2006, were selected from the Amgen Inc. clinical trials database. Exposure-adjusted rates of serious infections, opportunistic infections, malignancies, and deaths were reported by trial, indication, and dosage.
Rates of serious infections were generally similar between etanercept and controls. Overall rates of opportunistic infections and tuberculosis were low. The standardized incidence ratio (SIR) (95% CI) for malignancy was 1.00 (0.83-1.19) for all etanercept patients across all indications. The SIR for lymphoma for patients with rheumatoid arthritis was 3.45 (1.83-5.89); all other indications reported SIRs similar to those observed in the general population. The SIRs for cutaneous squamous cell carcinoma in patients with psoriasis relative to the general population with high or low sun exposure were 2.09 (1.27-3.22) and 4.96 (3.03-7.66), respectively. SIRs were less than 1.0 for all other indications regardless of sun exposure. Rates of melanoma and basal cell carcinoma were not significantly different from those in the general population. There was no increase in mortality associated with etanercept use relative to control populations.
These data support the overall tolerability of etanercept across approved indications.
Journal of drugs in dermatology: JDD 03/2011; 10(3):289-300. · 1.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of long-term etanercept treatment, with or without methotrexate, on growth in children with selected categories of juvenile idiopathic arthritis (JIA).
We conducted a 3-year, open-label, nonrandomized registry of 594 patients with polyarticular or systemic JIA treated with etanercept only, etanercept plus methotrexate, or methotrexate only. Height, weight, and body mass index (BMI) were assessed at baseline and at years 1, 2, and 3, using percentiles derived from US Centers for Disease Control and Prevention standardized growth charts.
Statistically significant increases in the mean height percentiles from baseline were observed in etanercept-treated patients at year 3 (4.8 percentile points) and in patients treated with etanercept plus methotrexate at years 1, 2, and 3 (2.4, 3.3, and 5.6 percentile points, respectively). Statistically significant increases from baseline in the mean weight percentiles were observed at years 1, 2, and 3 in both the etanercept group (7.4, 10.0, and 13.0 percentile points) and the etanercept-plus-methotrexate group (2.9, 6.9, and 8.4 percentile points, respectively). Statistically significant increases from baseline in the mean BMI percentiles were observed in both the etanercept group (range 9.6-13.8 percentile points) and the etanercept-plus-methotrexate group (range 2.1-5.2 percentile points). The mean height, weight, and BMI percentiles did not change significantly in patients in the methotrexate-only group.
Etanercept treatment, with or without methotrexate, may contribute to the restoration of normal growth in children with JIA.
[Show abstract][Hide abstract] ABSTRACT: To identify factors associated with radiographic progression at 52 weeks in patients with rheumatoid arthritis (RA) after 12 weeks of methotrexate (MTX) therapy.
The study population consisted of patients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO). Logistic regression analysis was used to identify clinical and laboratory assessments performed at Week 12 of MTX therapy that might be associated with Week 52 radiographic outcome (modified total Sharp score). Classification and regression tree (CART) modeling of the Week 12 assessments was used to determine the subgroups of patients with the best and worst radiographic outcomes.
A total of 169 patients were analyzed: 116 patients in the best radiographic outcome group and 53 patients in the worst radiographic outcome group. Logistic regression analysis showed that Week 12 C-reactive protein (CRP) level, erythrocyte sedimentation rate, tender joint count, swollen joint count (SJC), and Health Assessment Questionnaire scores were significantly associated with radiographic progression at Week 52 (p < 0.05 for each assessment). CART modeling showed that patients with Week 12 CRP > 0.67 mg/dl and SJC > 1 and patients with Week 12 CRP ≤ 0.67 mg/dl and SJC > 10 were likely to show the worst radiographic progression at Week 52. The CART model had a sensitivity of 85%, specificity of 60%, and overall classification accuracy of 68%.
In patients with RA, measures of CRP and SJC after 12 weeks of MTX therapy emerged as the factors most associated with radiographic progression at Week 52.
The Journal of Rheumatology 11/2010; 38(2):242-6. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: to report the rates of serious adverse events (SAE), serious infectious events (SIE), and events of medical interest (EMI) in patients receiving etanercept; to identify the risk factors for SAE, SIE, and EMI; and to report time to switching from etanercept therapy, reasons for switching, and time to restarting treatment with etanercept in patients with rheumatoid arthritis (RA) in US clinical practice.
adults ≥ 18 years of age who fulfilled the 1987 American Rheumatism Association criteria for RA were eligible for enrollment in 2 prospective, 5-year, multicenter, observational registries. RADIUS 1 (Rheumatoid Arthritis DMARD Intervention and Utilization Study) enrolled patients with RA who required a change in treatment [either an addition or a switch of a biologic or nonbiologic disease-modifying antirheumatic drug (DMARD)]. In RADIUS 2, patients with RA were required to start etanercept therapy at entry. Patients were seen at a frequency determined by their rheumatologist. RADIUS 1 and RADIUS 2 were registered under the US National Institutes of Health ClinicalTrials.gov identifiers NCT00116714 and NCT00116727, respectively.
in these patients, SAE, SIE, and EMI occurred at rates comparable to those seen in clinical trials. No unexpected safety signals were observed. Rates for SAE, SIE, and EMI in etanercept-treated patients were comparable to rates observed in patients receiving methotrexate monotherapy and did not increase with greater exposure to etanercept therapy.
the RADIUS registries provide a better understanding of the safety of etanercept in patients with RA in the US practice setting.
The Journal of Rheumatology 10/2010; 38(1):21-8. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the long-term safety and efficacy of etanercept therapy in rheumatoid arthritis (RA) patients.
Adult patients with early RA or longstanding RA received etanercept in open-label extension studies following initial double-blind trials of etanercept.
Of 558 early RA patients and 714 longstanding RA patients who received at least 1 dose of etanercept, a total of 194 early RA patients and 217 longstanding RA patients were treated with 25 mg of etanercept twice weekly through 10 years. Five opportunistic infections were reported: in early RA, 1 Candida septicemia; in longstanding RA, 1 herpes zoster, 1 atypical mycobacterium infection, 1 meningoencephalitis (unspecified), and 1 fungal sepsis (unspecified). Twenty-nine cases of sepsis occurred (10 early RA, 19 longstanding RA). Occurrence of all malignancies was similar to that expected in the general population, but the occurrence of lymphomas was higher than expected in the general population. Fourteen lymphomas (7 early RA, 7 longstanding RA) and 2 cases of demyelinating disease (1 early RA, 1 longstanding RA) were reported. Deaths occurred in 18 early RA patients and 43 longstanding RA patients. Both patient groups showed sustained improvement in American College of Rheumatology responses, swollen joint counts, Health Assessment Questionnaire disability index scores, and C-reactive protein levels.
Etanercept maintained therapeutic benefits beyond 10 years of therapy in both early RA and longstanding RA patients, suggesting that etanercept is well tolerated and effective as a long-term, continuous therapy for the treatment of RA, with a favorable risk/benefit ratio.
[Show abstract][Hide abstract] ABSTRACT: Liver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007.
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >1x upper limit of normal (ULN) were considered elevations and ALT/AST levels >2x ULN were considered abnormalities. Treatments included TNF-Is, methotrexate (MTX), leflunomide and other disease-modifying antirheumatic agents (DMARDs). Patients were censored after their first LFT elevation. Three analytical models were evaluated: (1) individual TNF-I vs non-biological DMARDs (primary model); (2) individual TNF-I plus MTX vs MTX monotherapy; and (3) limited to new users of individual TNF-I vs non-biological DMARDs. ORs for LFT elevations were estimated using generalised estimating equation logistic regression.
6861 patients (ADA: 849; ETN: 1383; INF: 1449) with 22 522 determinations were analysed. LFT elevations >1x ULN with TNF-I use were seen in 5.9% of AST/ALT determinations and abnormalities >2x ULN in 0.77%. In the primary model the adjusted ORs for LFT elevations >1x ULN were ADA 1.35 (95% CI 1.09 to 1.66), ETN 1.00 (95% CI 0.83 to 1.21) and INF 1.58 (95% CI 1.35 to 1.86). For 2x ULN, adjusted ORs were ADA 1.72 (95% CI 0.99 to 3.01), ETN 1.10 (95% CI 0.64 to 1.88) and INF 2.40 (95% CI 1.53 to 3.76). Similar results were obtained in other models.
The overall incidence of LFT elevations >1x ULN with TNF-I use was uncommon and abnormalities >2x ULN were rarely observed. Significant differences were most consistently observed with INF, less commonly with ADA and were not observed with ETN compared with comparator DMARDs.
Annals of the rheumatic diseases 05/2010; 69(9):1612-7. · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA).
Patients ages 2-18 years with rheumatoid factor (RF)-positive or RF-negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (> or =10 mg/m(2)/week [ approximately 0.3 mg/kg/week], maximum dosage 1 mg/kg/week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open-label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician's global assessment of disease activity and the pediatric total joint assessment.
A total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure-adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient-years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient-years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician's global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study.
These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication.
[Show abstract][Hide abstract] ABSTRACT: To assess uveitis (including iritis and iridocyclitis) incidence from clinical trials of etanercept in patients with ankylosing spondylitis (AS).
Clinical trials of etanercept in AS (four placebo-controlled; one active-controlled; three open-label) were examined for reports of uveitis. Between-group differences with confidence intervals (CIs) in the uveitis rates were calculated for the double-blind, active-controlled and long-term studies.
In placebo-controlled trials, the uveitis rate per 100 subject years (95% CI) for etanercept (8.6 (4.5 to 14.2)) was lower than that for placebo (19.3 (11.0 to 29.8), p = 0.03). In the active comparator trial, rates for etanercept and sulfasalazine were similar (10.7 (5.5 to 17.6) and 14.7 (6.4 to 26.5), respectively; p = 0.49). The long-term rate for etanercept, estimated from both placebo-controlled and open-label extension studies was 12.0 (10.0 to 14.1).
In subjects with AS, rates of uveitis events with etanercept were lower than with placebo in placebo-controlled trials and similar to sulfasalazine in an active comparator trial.
Annals of the rheumatic diseases 06/2009; 69(1):226-9. · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor (TNF) antagonists, including etanercept (a soluble TNF receptor) and infliximab (an anti-TNF monoclonal antibody) are used in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to evaluate the effectiveness and safety of 50 mg etanercept weekly in subjects with RA who have failed infliximab therapy.
This phase 4, multicenter, open-label, single-arm, 16-week observational study enrolled subjects who had experienced primary (failure to achieve an initial response) or secondary (failure to maintain an initial response) infliximab failures. Effectiveness was measured using European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria and laboratory assessments were used to evaluate levels of inflammation, lymphotoxin alpha, drug concentrations, and antibodies to infliximab. Safety endpoints included incidence of serious adverse events. Clinical trial registration: This trial was registered under U.S. National Institutes of Health ClinicalTrials.gov identifier NCT00099554.
At week 16, over half (62%; 95% CI = 55, 69) of all subjects in the trial achieved a good or moderate EULAR response (DAS28) with etanercept. Using ACR criteria, after 16 weeks of etanercept therapy, 45% (95% CI = 38, 52) of all subjects had achieved an ACR20 response. Benefits were noted in tender and swollen joint counts, subject and physician global assessments, joint pain, and the Health Assessment Questionnaire. Outcomes were similar between subjects with primary and secondary infliximab failures. Levels of lymphotoxin alpha did not appear to affect response to etanercept. Potential limitations included the lack of a washout period, short duration of the trial, and the number of subjects who did not receive all doses of etanercept.
In this open-label, uncontrolled study, subjects with moderate to severe RA who failed to respond or who lost their initial response to infliximab safely benefited from receiving etanercept.
Current Medical Research and Opinion 04/2009; 25(5):1131-42. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA).
Patients with JRA who previously participated in a randomized controlled trial (RCT) of etanercept were eligible to receive etanercept in a long-term open-label extension (OLE) trial. Safety end points included the incidences of serious adverse events (SAEs), medically important infections (MIIs), and death. Efficacy end points included the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement.
Of the 69 patients originally enrolled in the RCT, 58 (84%) participated in the OLE, for a total of 318 patient-years of etanercept exposure. A total of 42 of the 58 patients (72%) entered the fourth year of continuous etanercept treatment, and 26 patients (45%) entered the eighth year. Sixteen patients (23% of those entering the RCT) reported 39 SAEs. The overall rate of SAEs (0.12 per patient-year) did not increase with long-term exposure to etanercept. The rate of MIIs (0.03 per patient-year) remained low; 1 new MII was reported in patients with > or =5 years of etanercept exposure. No cases of tuberculosis, opportunistic infections, malignancies, lymphomas, lupus, demyelinating disorders, or deaths were reported. An ACR Pedi 70 response or higher was achieved by 100% of patients with 8 years of data (11 of 11) and by 61% of patients according to the last observation carried forward data (28 of 46).
These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients. Improvements in the signs and symptoms of JRA were also maintained for up to 8 years.
[Show abstract][Hide abstract] ABSTRACT: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years.
Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated.
The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age.
Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.
Annals of the Rheumatic Diseases 04/2006; 65(3):379-84. · 9.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare etanercept-induced improvement in disability of patients with recent onset of rheumatoid arthritis (RA) to that of patients with established RA.
Health Assessment Questionnaire (HAQ) scores were collected over 3 years in 2 groups of patients with RA who were treated with etanercept. The first group consisted of 207 patients with recent onset RA (mean duration of 1 year) who had not previously received methotrexate, and the second group consisted of 464 patients with established RA (mean duration of 12 years) who had failed one or more disease-modifying antirheumatic drugs.
Baseline demographics and disease characteristics were similar in the 2 groups, except for HAQ scores and C-reactive protein levels, which were higher in the established RA group. Patients in both groups showed rapid and sustained clinical responses with etanercept therapy, but patients with recent onset RA showed significantly greater improvement in HAQ scores compared with patients with established RA. The difference in magnitude of HAQ score improvement between groups was observed as early as week 2 after initiation of etanercept and persisted throughout the 3-year time frame. At year 3, significantly more patients with recent onset RA had a HAQ score of zero (26%) versus those with established RA (14%, p = 0.0095).
Although etanercept therapy significantly improved disability scores in both groups, patients with recent onset of RA showed greater benefit in HAQ scores than patients with established RA. These results support prompt treatment of RA at an early stage of disease to minimize patient disability.
The Journal of Rheumatology 09/2004; 31(8):1532-7. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutics used to treat inflammatory diseases, including psoriatic arthritis (PsA), may potentially interfere with normal immune system function. Immune system function can be assessed by evaluating response to vaccination. We assessed the ability of patients with PsA treated with etanercept to produce antibodies in response to pneumococcal antigen challenge.
Patients with PsA (n = 205) were stratified by methotrexate (MTX) use and randomly assigned to receive either placebo or etanercept 25 mg twice weekly by subcutaneous injection. After 4 weeks of treatment with study drug, a 23-valent pneumococcal vaccination was administered. Antibody levels to 5 antigens (9V, 14, 18C, 19F, and 23F) were measured by ELISA before and 4 weeks after vaccination in 184 patients. The proportion (%) of patients with 2- and 4-fold increases in antibody titers was analyzed.
Patients treated with etanercept or placebo had similar responses to the vaccine. A 2-fold increase in titer to at least 2 antigens was achieved by 67% of patients, and a 4-fold increase to at least 2 antigens was achieved by 47% of patients. Approximately 20% of patients in each group failed to show a 2-fold response to any antigens. Logistic regression analysis showed MTX use and age were predictors of a poor response.
Patients with PsA treated with etanercept were able to produce antibodies in response to pneumococcal vaccination. Patients receiving MTX had lower mean antibody levels in response to the vaccine. There was no increased risk of poor response with etanercept treatment given alone or with MTX.
The Journal of Rheumatology 08/2004; 31(7):1356-61. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 3% of the US population over the age of 65 years has rheumatoid arthritis (RA). We compared the safety and efficacy of etanercept (Enbrel) in patients with RA who were > or = 65 years to those < 65 years in open-label and double-blind, randomized clinical trials.
Patients from 4 double-blind, randomized controlled trials and 5 open-label trials were included in this retrospective analysis. Patients were grouped by age (< 65 or > or = 65 yrs) at time of study entry. All patients received etanercept subcutaneously twice weekly. Improvement in signs and symptoms was assessed by the proportion of patients who achieved the American College of Rheumatology definition of improvement (ACR 20). The ACR 50 and ACR 70 responses were calculated in an analogous fashion. Safety was assessed at regularly scheduled visits.
Of 1128 patients enrolled in etanercept trials, 197 (17%) were > or = 65 years of age. Clinical response was rapid and sustained and did not differ between age groups. At one year, 69% of patients < 65 years and 66% of patients > or = 65 years met the ACR 20. Forty percent of the patients > or = 65 years met the ACR 50 and 17% met the ACR 70. Etanercept was well tolerated. Although injection site reactions, headache, and rhinitis occurred somewhat more frequently in younger patients, the overall rates and types of other adverse events were comparable in both groups.
Etanercept is a new treatment option for older patients with RA and has substantial benefit and comparable safety regardless of patient age.
The Journal of Rheumatology 04/2003; 30(4):691-6. · 3.26 Impact Factor