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ZusammenfassungUnter dem Begriff der Spondyloarthritiden wird eine Vielzahl von klinisch unterschiedlichen Krankheitsbildern zusammengefasst. Neben der klassischen ankylosierenden Spondylitis geht es über die Psoriasis, Psoriasis-Arthritis, zu einer akuten anterioren Uveitis, reaktiven Arthritis oder einer Arthritis in Verbindung mit Colitis ulcerosa oder Colitis ulcerosa und Morbus Crohn.

Objectives To evaluate retention, efficacy, and safety of subcutaneous (SC) abatacept over 2 years in patients with moderate-to-severe RA in the Abatacept SubCutaneOus in Routine clinical practicE (ASCORE) study. Methods Patients with RA who initiated SC abatacept 125 mg once weekly were enrolled in the international, observational, prospective multicentre ASCORE study into biologic-naïve or ≥ 1 prior biologic failure cohorts. Primary endpoint: abatacept retention rate at 2 years. Secondary endpoints: proportion of patients with good/moderate EULAR response rates based on DAS28 (ESR), low disease activity and/or remission according to DAS28 (ESR; ≤ 3.2/ Results Overall, 47% of patients remained on abatacept for 2 years, irrespective of treatment line. Higher abatacept retention rates were associated with lower prior biologic exposure. Generally, clinical outcomes showed that the proportion of patients with low disease activity/remission was higher in biologic-naïve patients (vs biologic-failure) and similar in those with 1 and ≥ 2 prior biologic failures. In patients on treatment at 2 years, good/moderate EULAR response rates of ~ 80% were consistently noted irrespective of prior biologic exposure. Across treatment lines, retention was greater in patients with seropositive (vs seronegative) RA. Patients with rheumatoid factor/anti-citrullinated protein antibody single-positive RA who were bio-naïve had higher retention than patients who were bio-experienced. Conclusions In the ASCORE study, SC abatacept retention was 47% at 2 years with good clinical outcomes and was well-tolerated in the real-world setting. Abatacept retention and clinical response rates were higher in patients who received abatacept as an earlier- versus later-line biologic drug treatment and in those with seropositive RA. Trial registration ClinicalTrials.gov, NCT02090556.

Several international guidelines for treatment and prophylaxis of glucocorticoid-induced osteoporosis (GIO) have been published. Consistent with the development of new therapeutic agents, a different approach to treatment can be recognized depending on the year of publication. Also, new insights for the postmenopausal osteoporosis leave their marks on recent guidelines. The working committee on Osteology of the Austrian Society for Rheumatology and Rehabilitation (OGR) sifted through actual guidelines and recent literature on the topic to develop recommendations for the prophylaxis and treatment of the GIO.

Zusammenfassung Schwangerschaft und rheumatische Erkrankungen haben viele Beruhrungspunkte. Einige rheumatische Erkrankungen sind deutlich hormonabhangig und konnen wahrend und nach der Schwangerschaft erstmals auftreten. Auch die Zu- oder Abnahme der Krankheitsaktivitat wahrend der Schwangerschaft wird bei den einzelnen rheumatischen Erkrankungen regelmasig beobachtet. Generell stellen aber die rheumatischen Erkrankungen keine Kontraindikationen fur eine geplante Schwangerschaft dar. Bei den meisten der Medikamente sollte wahrend der Therapie keine Schwangerschaft eintreten und deshalb eine sichere Verhutung erfolgen. Nur wenige Medikamente konnen wahrend der Schwangerschaft problemlos eingenommen werden. Neben Kortison gibt es inzwischen gute Sicherheitsdaten fur Chloroquin und Sulfasalazin und einige Biologika, wobei die Einnahme immer interdisziplinar (Rheumatologie, Gynakologie und Patientin) abgewogen werden sollte.

The increasing rate of hip fractures is giving rise to a number of socioeconomic problems for the aging community. In addition to being unable to resume their previous living habits, many patients fail to achieve full functional recovery after the fractures. Total hip arthroplasty (THA) is a successful operation for the majority of patients with all forms of hip fractures. Dislocation and aseptic loosening are the major reasons for revisions. An additional problem post-THA is the rate of heterotopic soft tissue calcification after total hip arthroplasty, resulting in severely impaired function, pain, and a reduced range of hip motion. In an open study, 37 women who had undergone cementless total hip arthroplasty after accidental hip fractures were treated twice daily with 200 IU salmon calcitonin nasal spray for 12 months. Simultaneously, the patients received one bag of 1000 mg calcium plus 880 IU vitamin D daily throughout the treatment period of 1 year. A parallel group of 38 women with a similar clinical status in terms of hip fractures and cementless total hip arthroplasty were treated with only one bag of 1000 mg calcium plus 880 IU vitamin D daily through the treatment period. The results of this 12-month clinical trial show that 200 IU salmon calcitonin nasal spray per day promotes general independence from foreign assistance, mobility, and fear of further falls in postmenopausal elderly women following THA. Treatment with a salmon calcitonin nasal spray reduces bone turnover serum markers, loss of further bone density, and pain. Additionally, calcitonin promoted the repair of hip fractures and, as a coincidence finding, was associated with a significantly reduced rate of refractures as well as periprosthetic ossifications.

Zusammenfassung Biologika sind in Europa seit etwa einem Jahrzehnt im Einsatz. Ursprunglich fur die Therapie von Blutvergiftungen entwickelt, bekampfen die molekularbiologisch hergestellten Medikamente heute erfolgreich zum Beispiel die rheumatoide Arthritis (RA): Sie blockieren gezielt die von der korpereigenen Abwehr gesteuerten entzundlich-rheumatischen Vorgange im Gelenk. Mittlerweile sind mehrere Wirkstoffe auf dem Markt und kontrollierte klinische Studien belegen eine hohe Wirksamkeit und ein gutes Sicherheitsprofil. Lungenentzundungen oder Gurtelrose gehoren zu den moglichen, wenn auch seltenen Folgen einer solchen Therapie. Biologika erfordern auch eine genaue Uberwachung bei Menschen, die unterschwellig mit Tuberkulose infiziert sind.

Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis–trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28–50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r = 0.91, P

Derivation of the 2-aminobenzylstatine containing HIV-1 proteinase (PR) inhibitor I led to a series of compounds with considerably improved antiviral activity, the most potent derivatives inhibiting HIV-1 with IC50 values below 25 nM. This was achieved by the combination of several structural modifications, most prominently by introduction of a benzimidazole heterocycle into the inhibitor. The mode of action of the 2-aminobenzylstatine PR inhibitors was demonstrated to be inhibition of gag precursor processing. The antiviral efficacy of the PR inhibitors was demonstrated in various cell lines, in primary T4 lymphocytes and in monocytes. The most potent compound (XI) inhibited replication of several HIV-1 clinical isolates in primary cells with IC50 values of 8 to 23 nM. The analysis of the pharmacokinetic behaviour of compounds I and VII revealed blood half-lives in rodents in the range of about 1.5 h. Compound I also showed appreciable oral uptake in mice (18%), but yielded no detectable blood levels in rats after oral administration. Benzimidazole containing compounds like VII were not orally bioavailable to a significant extent, neither in mice nor in rats. Thus, while introduction of a benzimidazole group into the PR inhibitors was a successful structural modification with regard to antiviral activity in cell culture, it completely abolished oral bioavailability.

Several international guidelines for treatment and prophylaxis of glucocorticoid-induced osteoporosis (GIO) have been published. Consistent with the development of new therapeutic agents, a different approach to treatment can be recognized depending on the year of publication. Also, new insights for the postmenopausal osteoporosis leave their marks on recent guidelines. The working committee on Osteology of the Austrian Society for Rheumatology and Rehabilitation (ÖGR) sifted through actual guidelines and recent literature on the topic to develop recommendations for the prophylaxis and treatment of the GIO.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p0.01) and QCT (5.7%, p0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p0.0001), total hip (10.8%, p0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p0.0001).Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

The identification of circulating autoantibodies contributes to the correct diagnosis as well as to the follow-up of rheumatic diseases. Some autoantibodies are even included in diagnostic and classification criteria for these types of autoimmune diseases. There are several relatively specific screening and identification methods for the measurement of autoantibodies available. The type of assay crucially influences the diagnostic value of the parameters. In general, routine laboratories should prefer enzyme immunoassays (ELISA) using well characterized antigens, although ELISA tests tend to produce more false-positive and true weakly positive results, which reduce their positive predictive value. Therefore one should be aware that laboratory results can only be properly interpreted when there is a correlation with the clinical situation and when the limitations of the technologies used for autoantibody identification have been taken into consideration. A diagnostic algorithm consisting of screening and identification steps should be established by each laboratory in order to create a rational, evidence-based and cost-effective basis for the diagnosis of rheumatic diseases.

Because of the importance of macrophages in the pathogenesis of the disease caused by HIV, we investigated the efficacy of various anti-HIV drugs in human primary macrophages acutely or chronically infected by this virus. The results obtained for acutely infected macrophages show that dideoxynucleosides (AZT, ddI, and ddC), interferon-α and -γ, mismatched double-stranded RNA, Tat inhibitor, phosphorothioate antisense, and inhibitors of HIV protease, all significantly inhibit virus replication at concentrations far below those toxic for the cells. However, in macrophages in which proviral DNA is already integrated (chronically infected macrophages), only the three inhibitors of HIV protease induced significant virus inhibition at concentrations 100 or more times higher than those effective in acutely infected macrophages. Treatment of macrophages with macrophage colony-stimulating factor does not affect the anti-HIV efficacy of protease inhibitors. These results suggest that therapeutic strategies with activity for macrophages, including inhibitors of HIV protease, are worth pursuing in patients with HIV infection. J. Leukoc. Biol. 56: 381–386; 1994.

Neutrophil activating peptide 1, or interleukin-8 (NAP-1, IL-8), was isolated almost simultaneously by several groups as a neutrophil chemotactic or activating peptide from supernatants of endotoxin stimulated monocytes (1–5). The major form with 72 amino acids, and an approximate molecular weight of 8.4 kD, has since been shown to have activities on a variety of different cell types. It is chemotactic for neutrophils (PMN) and lymphocytes both in vitro and in vivo (6,2,4,7), and has been shown to stimulate PMN in vitro to degranulate and to exhibit respiratory burst (8,9), and thus has the basic attributes of an inflammatory mediator. Further actions which could be of great importance in inflammatory processes are chemotactic attraction of basophils, the triggering of IL-3 primed basophils to release leukotrienes and histamine (10), spasmogenic activity on airway smooth muscle (11), and effects on PMN adherence to endothelial cells (12).