Etanercept is Effective and Halts Radiographic Progression in Rheumatoid Arthritis and Psoriatic Arthritis: Final Results from a German Non-interventional Study (PRERA).

INTRODUCTION: Etanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36 months in outpatient care in Germany (NCT01623752). METHODS: Patients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12-18 (Rx2), and/or months 30-36 (Rx3). Historic radiographs (Rx0) taken 12-48 months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated. RESULTS: Overall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed. CONCLUSIONS: This was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are diseases in which inflammation can lead to damage in the joints. X-ray images can show whether the disease gets worse; this is called radiographic progression. Etanercept is a drug that acts on the body's immune system and can reduce inflammation in the joints. In clinical studies, radiographic progression was slower in people with RA or PsA who received etanercept compared with people who received another drug called methotrexate. In this study, we wanted to know how radiographic progression changes in people in Germany who receive etanercept as part of their routine treatment. A total of 1378 people with RA and 440 people with PsA received etanercept for up to 36 months. We observed little to no radiographic progression for most people during the study. Radiographic progression was worse before people started taking etanercept. More people had no radiographic progression while taking etanercept compared with before they started treatment. The proportion of people who responded to treatment with etanercept as measured by the number of painful joints increased throughout the study. Overall, people felt that their health improved after they started taking etanercept.This was the first large study in which we investigated how radiographic progression changes when people with RA or PsA start taking etanercept as part of their routine treatment. We observed a slowing or halting of radiographic progression in most people and an improvement in their overall health.

Effectiveness of Etanercept in Rheumatoid Arthritis: Real-World Data from the German Non-interventional Study ADEQUATE with Focus on Treat-to-Target and Patient-Reported Outcomes.

BACKGROUND: For rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks. OBJECTIVES: This German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52). METHODS: A total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively. RESULTS: The proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected. CONCLUSIONS: A considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02486302.

Physicians measure response to treatment of rheumatoid arthritis using a disease activity score (DAS28). People with a DAS28 of less than 2.6 have very few to no symptoms (also called remission). People with a DAS28 of 3.2 or less, called low disease activity, may experience mild symptoms. When people do not respond to treatment after 12 weeks, it is usually recommended to prescribe a different treatment. Researchers do not know how many people who do not respond after 12 weeks would respond if treatment were continued. A total of 824 German people with rheumatoid arthritis who received a drug called etanercept for up to 52 weeks took part in this study. Researchers wanted to know how many people had remission or low disease activity after 12 weeks and 24 weeks of treatment.After 12 weeks, 24 in 100 people had remission; this increased to 31 in 100 people after 24 weeks. Thirty-nine in 100 people had low disease activity after 12 weeks; this increased to 45 in 100 people after 24 weeks. The number of people with remission or low disease activity increased with longer treatment (up to 52 weeks). People needed less additional treatment with a type of drug called glucocorticoids. The people in this study experienced side effects that were similar to those reported by people who took etanercept in previous studies.The researchers concluded that a considerable proportion of people responded to treatment with etanercept after 12 weeks. This proportion increased when treatment was continued for longer than 12 weeks.

Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.

OBJECTIVE: To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. METHODS: A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. RESULTS: Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. CONCLUSION: While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

Etanercept is effective as monotherapy or in combination with methotrexate in rheumatoid arthritis: subanalysis of an observational study.

Approximately 30% of patients with rheumatoid arthritis receiving biological disease-modifying antirheumatic drugs (bDMARDs) take them as monotherapy. Although etanercept (ETN) monotherapy has been evaluated in clinical trials, data in the real-world setting are sparse. We compared the efficacy and safety of ETN, given alone or in combination with methotrexate (MTX), in routine clinical practice. This was a subanalysis of patients who received either ETN alone or ETN + MTX during a 52-week prospective, observational study conducted at 329 German centers. The primary endpoint was "Funktionsfragebogen Hannover" (Hannover Functional Ability Questionnaire [FFbH]; low FFbH = worse function) functional remission at week 26 and week 52. Secondary endpoints included the 28-joint count Disease Activity Score (DAS28), DAS28 remission (DAS28 < 2.6), and adverse events (AEs). Participating centers applied ETN monotherapy in 43.1% of patients and ETN + MTX in 56.9%. A smaller proportion of patients achieved FFbH functional remission with ETN vs ETN + MTX (31.9%, 95% confidence interval [CI] 29.1-34.9% vs 39.8%, 37.2-42.5%, respectively; p < 0.001) at 26 weeks and at 52 weeks (38.4%, 35.1-41.7% vs 44.3%, 41.5-47.2%, respectively; p = 0.007). After 52 weeks, the mean DAS28 (±SD) decreased from 5.5 ± 1.3 to 3.4 ± 1.4 (ETN) vs 5.3 ± 1.3 to 3.2 ± 1.3 (ETN + MTX) and DAS28 remission was achieved by 32.5% (95% CI 29.0-36.1%) of patients with ETN vs 38.8% (35.8-41.9%; p = 0.007) with ETN + MTX. Overall, 20.6 (ETN) and 19.7% (ETN + MTX) of patients reported treatment-related AEs. Patients received ETN monotherapy almost as often as ETN + MTX. ETN + MTX appeared marginally more effective than ETN monotherapy in some, but not all, outcomes measured.

Therapy of 1,025 severely ill patients with complicated infections in a German multicenter study: safety profile and efficacy of tigecycline in different treatment modalities.

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum ß-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Antiparkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease.

N-methyl-D-aspartate (NMDA) receptor antagonists have antiakinetic and antidyskinetic effects in animals models of Parkinson's disease (PD). However, non-selective inhibition of NMDA receptors throughout the central nervous system may result in undesired effects such as ataxia and psychosis. We therefore studied Ro 25-6981, an activity-dependent antagonist of NMDA receptors containing the NR2B subunit which are predominantly expressed in the striatum. Ro 25-6981 induced contraversive rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats without stimulating locomotion in normal rats and reversed parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-treated common marmosets. Due to the small number of marmosets, there were no significant differences between Ro 25-6981 and vehicle though there was a significant trend toward differences, as shown by the Page test. Furthermore, Ro 25-6981 potentiated the action of levodopa in both species and attenuated the maximal levodopa response in 6-OHDA-lesioned rats chronically treated with levodopa without reducing the overall response. Ro 25-6981 also potentiated the action of the dopamine receptor agonists apomorphine, A68930 and quinpirole in 6-OHDA-lesioned rats. The present observations suggest a therapeutic potential of NR2B-selective NMDA receptor antagonists in the management of PD.