With the increasing use of etanercept for juvenile idiopathic arthritis (JIA) new possible adverse events are reported including new autoimmune diseases. Our purpose was to examine if the incidence of inflammatory bowel disease (IBD) in patients with JIA using etanercept is higher than in the healthy age-matched population. We give the clinical characteristics of the IBD in patients with JIA using etanercept.
The national JIA registries for etanercept of The Netherlands, Germany, Finland, Denmark, and Italy were searched for patients with JIA and IBD. The total number of patient-years was used to calculate incidence. The physicians of the identified patients were asked to give clinical details.
Thirteen cases of IBD in JIA patients were identified in the registries between 1999 and 2008. The IBD incidence in JIA patients while using etanercept was 362 per 100,000 patient-years under etanercept, about 43 times higher than in the general pediatric population. Clinical presentation of IBD in JIA patients using etanercept was similar to that in non-JIA patients. The median time between onset of JIA and onset of IBD was 6 years and 10 months. The time between the start of etanercept and the first appearance of IBD symptoms was between 9 days and 4.5 years.
The incidence of IBD in JIA patients using etanercept seems to be markedly increased, analyzing data from European registries. This incidence of IBD in the etanercept registries cannot be compared to the incidence of IBD in JIA patients using other treatment without etanercept, because such registries do not exist yet in all European countries. These findings are in keeping with a report of 8 new IBD cases occurring in French children with JIA using etanercept. These findings illustrate the need for large international disease-specific registries focused on outcome and pharmacovigilance.
To describe the longterm effectiveness and safety of etanercept in Canadian patients with psoriatic arthritis (PsA), treated over 24 months in clinical practice.
Patients with active PsA (= 3 tender and = 3 swollen joints) were recruited from 22 centers. Etanercept was administered at 50 mg/week subcutaneously. In addition to clinical assessment of skin and joint disease, conducted at baseline and at Months 6, 12, 18, and 24, regular patient interviews were conducted by telephone. Patient responses related to health status, disability, and work productivity were scored using the patient global assessment tool, the Health Assessment Questionnaire (HAQ), the Health and Labour Questionnaire (HLQ), and the Fatigue Severity Scale.
Out of 110 patients, 71 (65%) maintained etanercept treatment through the end of our study. All clinical measures of disease severity, including joint tenderness/pain, joint swelling, and Psoriasis Area and Severity Index score, improved significantly between baseline and Month 6 of etanercept treatment and remained constant thereafter. By the end of our study, 79% of patients achieved a Psoriatic Arthritis Response Criteria response, and 56% of patients achieved a 0.5-point improvement on HAQ, indicating clinically significant improvement in disability; 14% of patients finished our study free of disability (HAQ = 0). Patients' work productivity and fatigue improved significantly in parallel with these clinical and functional improvements.
Continuous treatment with etanercept over 2 years in a clinical setting improved clinical symptoms of PsA while reducing fatigue, improving work productivity, and ameliorating or eliminating disability.
OBJECTIVE: To explore the feasibility of prospectively monitoring treatment efficacy and tolerability of infliximab, etanercept, and leflunomide over a two year period in patients with established rheumatoid arthritis (RA) in clinical practice using a structured protocol. METHODS: All patients with RA at seven centres in southern Sweden, for whom at least two disease modifying antirheumatic drugs, including methotrexate, had failed or not been tolerated, who started treatment with either infliximab, etanercept, or leflunomide were included. They were evaluated at predefined times using a standardised protocol including items required for evaluating response to the American College of Rheumatology (ACR) or EULAR criteria. All adverse events were recorded using World Health Organisation terminology. Concomitant treatment and survival while receiving a drug were recorded. RESULTS: During the study 166 patients were treated with etanercept, 135 with infliximab, and 103 with leflunomide. Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor (TNF) blockers. The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis. Thus 79% and 75% continued to receive etanercept or infliximab compared with 22% of patients who started leflunomide after 20 months. The spectrum of side effects did not differ from those previously reported in the clinical trials. The initial two year experience of a protocol for postmarketing surveillance of etanercept, infliximab, and leflunomide shows that a structured protocol with central data handling can be used in clinical practice for documenting the performance of newly introduced drugs. CONCLUSIONS: Efficacy data for the TNF blockers comply with results in clinical trials, whereas leflunomide appeared to perform worse than in clinical trials. Prolonged monitoring is required to identify possible rare side effects.
Although etanercept is well tolerated and effective in moderate-to-severe plaque psoriasis, data are limited in Canadian practice settings.
To assess the effectiveness and safety of etanercept in Canadian patients with moderate-to-severe plaque psoriasis (Physician Global Assessment [PGA] = 3) in routine practice.
A 1-year, multicenter, open-label trial of 246 patients enrolled from March 2006 to July 2009 was conducted. Patients received etanercept 50 mg subcutaneously twice weekly for 3 months and then 50 mg once weekly for 9 months. The primary end point was the proportion of patients achieving a PGA score = 2 at month 12. Secondary end points included the proportion of patients achieving PGA score = 2 at months 3, 6, and 9 and change from baseline at month 12 for Patient Global Assessment (PtGA), body surface area, and Dermatology Life Quality Index (DLQI). Adverse events were reported.
At month 12, 73.5% (95% CI 67.2-79.1) achieved a PGA score = 2. The response was similar regardless of the previous response to systemic or phototherapy. The proportion of patients achieving this score improved from 2.2% (95% CI 0.3-4.2) at baseline to 73.5% (95% CI 67.2-79.1) at 12 months. At 12 months, patients with a DLQI score of 0 or = 5-point improvement was 28.8% (95% CI 22.9-34.7) and 47.3% (95% CI 40.8-53.9), respectively. No new safety signals were reported.
The majority of this Canadian population demonstrated a meaningful improvement in PGA and DLQI scores over 1 year.
To study (i) the drug utilization pattern of anti-rheumatic drugs in pregnant women and expectant fathers and (ii) the association between the use of anti-rheumatic drugs during pregnancy and the risk of congenital malformations.
Pregnancies registered in the Medical Birth Registry of Norway (MBRN) were linked to the Norwegian Prescription Database (NorPD) in the period 2004-2007. Prescriptions for anti-rheumatic drugs issued to women 3 months prior to and during pregnancy and to men 3 months prior to conception were identified. Congenital malformations were recorded according to the European Surveillance of Congenital Anomalies (EUROCAT) guidelines.
In 154,976 singleton pregnancies, 1461 of the women (0.9%) and 1198 (0.8%) of the known fathers (150,530) were dispensed anti-rheumatic drugs at least once during the study period: 723 had non-steroidal anti-inflammatory drugs (NSAIDs), 633 prednisolone (CS), 119 sulfasalazine (SASP), 101 azathioprine (AZA), 58 hydroxychloroquine (HQC), 37 etanercept (ETAN), eight methotrexate (MTX), two leflunomide (LEF), and three adalumimab (ADA). Odds ratios (ORs) for malformations in children born of women (w) or men (m) who had received the drugs were OR(w) = 1.06 [95% confidence interval (CI) 0.85-1.32] and OR(m) = 1.19 (95% CI 0.93-1.51), respectively, and for major malformation OR(w) = 1.05 (95% CI 0.79-1.40) and OR(m) = 1.26 (95% CI 0.93-1.71), respectively. None of the children whose mother had received MTX, LEF, ETAN, or ADA were reported to be born with major malformations.
This study revealed no major malformations of the alert drugs MTX, LEF, ETAN, or ADA. Although the numbers are limited, this provides important population-based information to both expectant parents and prescribers.
OBJECTIVES: To describe a nationwide system for postmarketing follow up of new antirheumatic drugs in Sweden, and to analyse safety and effectiveness in an etanercept treated patient cohort. METHODS: Etanercept became available in Sweden for prescribing on a named patient basis in 1999. All patients treated were included in a follow up of intensified adverse event reporting and recording of clinical outcome during 24 months, according to the EULAR core set. RESULTS: The mean (SD) disease activity score (DAS 28) value at inclusion among 820 patients recruited on a named patient basis during year 1 was 5.99 (1.19). After two years, 21% (n = 172) of these patients had discontinued the treatment. Of the remaining 648 patients, 68% (n = 442) responded to the treatment. However, in 55% of the responders, the disease activity was intermediate or high (mean DAS 28, 3.37 (1.20)). In all, 540 adverse events were reported in 421 adverse drug reaction (ADR) reports, in 294 patients. The events in 80 reports (19%) were serious. Twenty two per cent of the events were infections, of which 24% (n = 29) were serious. The incidence of serious adverse events remained constant over time. CONCLUSIONS: At start of etanercept treatment, patients had high disease activity. Activity remained high in a large proportion of the responding patients. Although serious ADRs occurred during late phases of treatment, no unexpected safety problems arose. No specific indicators of ADR risk were found. The monitoring system that was established may be useful in future postmarketing surveillance.