[Phase IV non-interventional studies in the treatment of rheumatoid arthritis with biologicals in Germany : real-life clinical practice data]. / Nichtinterventionelle Phase-IV-Studien zur Behandlung der rheumatoiden Arthritis mit Biologicals in Deutschland : Praxisbezogene klinische Daten.

BACKGROUND: In contrast to the restrictive nature of randomised controlled trials (RCT), non-interventional studies (NIS) investigate the features of a therapy in daily clinical practice. The observational plan of NIS does not dictate a treatment strategy, but is based on the product label. Unlike RCT, NIS therefore have no actual inclusion and exclusion criteria, allowing the study of broad heterogeneous patient populations. METHODS: NIS carried out in Germany with support from the pharmaceutical industry and investigating the use of biologics for the treatment of rheumatoid arthritis were identified and their findings were compared with those from the RCT of the respective biologic. RESULTS: Analysis of the identified NIS revealed the following: (1) populations in NIS were on average more than twice as large as in RCT, (2) patient characteristics in NIS and RCT were different, (3) the effectiveness of biologics in NIS was comparable to the efficacy observed in RCT, and (4) NIS collected supplementary data, e.g. on usage and dosing in clinical practice. CONCLUSION: NIS represent an important tool for the assessment of daily clinical practice. Despite methodological drawbacks, NIS provide valuable data that contribute to a more complete picture of the value of treatment with biologics. The English version of this article is available at SpringerLink (under "Supplemental").

Rapid alleviation of signs and symptoms of rheumatoid arthritis with intravenous or subcutaneous administration of adalimumab in combination with methotrexate.

OBJECTIVE: This randomized, placebo-controlled, double-blind, Phase 1 study assessed the magnitude, onset, and duration of response with intravenous (i.v.) and subcutaneous (s.c.) adalimumab (Humira, Abbott Laboratories) combined with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite previous MTX therapy. METHODS: Fifty-four patients were randomized to two injections of i.v. or s.c. adalimumab (1 mg/kg) or placebo while continuing on MTX (mean dose, 15.7 mg/week). Dosing intervals were determined by the European League Against Rheumatism (EULAR) response criteria, and were allowed to range from 1 to 3 months. Efficacy was mainly assessed using the EULAR response criteria and the American College of Rheumatology (ACR) response criteria. RESULTS: Moderate EULAR response was achieved at least once within 29 days after the first injection in 83% and 61% of patients receiving i.v. and s.c. adalimumab respectively, compared with 44% for placebo [probability (p) < or = 0.05 for i.v. adalimumab versus placebo]. A 20% improvement in disease activity according to the ACR criteria (ACR20 response) was achieved by 72% and 67% of patients receiving i.v. and s.c. adalimumab respectively, compared with 28% for placebo (p < or = 0.01 and p < or = 0.05, respectively, versus placebo). By Day 15 after the first and second injections, statistically significant moderate EULAR and ACR20 response rates were achieved with either i.v. or s.c. adalimumab compared with placebo (p < or = 0.05). The mean times to second injection for i.v. adalimumab, s.c. adalimumab, and placebo were 42.2 days (range: 27-84 days), 38.3 days (range: 26-85 days), and 28.4 days (range: 26-32 days), respectively (minimum time allowed by the protocol between the first and second injections was 4 weeks). Adalimumab in combination with MTX was well tolerated, with no patients being withdrawn because of adverse events. CONCLUSION: Either i.v. or s.c. adalimumab added to MTX significantly improved the signs and symptoms of RA compared with MTX alone. Subcutaneously administered adalimumab appeared to provide a response that was as great, as rapid, and as enduring as that with i.v. adalimumab.

[Concomitant manifestation of ochronosis and chronic polyarthritis in a patient]. / Gemeinsames Auftreten von Ochronose und chronischer Polyarthritis bei einer Patientin.

Ochronosis is rare disorder of tyrosin catabolism with an autosomal, recessive trait. Clinical signs predominantly affect the locomotor system. Inflammatory episodes in large joints can mimick Rheumatoid Arthritis (RA). Brownish discoloration of sclerae and cartilage is characteristic, diagnosis is confirmed by typical changes of spinal X-rays and the findings of homogentisic acid in urine samples. We describe a case of a 53 year old female patient with ochronosis and a second diagnosis of RA.

Impaired fibrinolytic capacity and tissue plasminogen activator release in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA).

To assess the role of the fibrinolytic system in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we determined the components of this system in a retrospective study, including 16 patients with restenosis (gr. A) and 19 patients with long-term success (gr. B). In both groups at baseline fibrinolytic activity (FA) is unchanged, whereas tissue plasminogen activator antigen (tPA-Ag) is significantly increased (gr. A: 147.0%; gr. B: 139.8%; p less than 0.01). Fibrinolytic capacity (FC) and tPA-Ag release are significantly reduced in the restenosis group (FC: 46.5%, p less than 0.05; tPA-Ag release: 48.3%, p less than 0.01) compared to normal controls as well as to gr. B (FC: 84.3%, p less than 0.05; tPA-Ag release: 79.0%, p less than 0.05). Relating to the contact activation system, F XII (79.5%, p less than 0.05) is significantly, and F XI (82.3%) is clearly reduced in gr. A. Protein C (PC) is significantly elevated in gr. B (117.5%, p less than 0.05). There is a negative correlation between plasminogen activator inhibitor (PAI 1) and HDL-cholesterol (r = 0.37, p less than 0.05). It appears, that there is a typical pattern of defective fibrinolysis in patients with restenosis after PTCA and that this might be a pathogenetic factor in the development of restenosis.