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Objectives: To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine). Methods: Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years. Results: Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p= 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively). Conclusion: Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Objective.To investigate sex differences in connection with the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).Methods.A total of 440 patients with AS (294 men; 146 women) initiating a first TNFi in the prospective Swiss Clinical Quality Management Cohort were included. We evaluated the proportion of patients achieving the 20% and 40% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued TNFi were considered nonresponders. Logistic regression analyses were performed to adjust for important predictors of response.Results.Compared to men, female patients had lower mean C-reactive protein levels, better spinal mobility, and more peripheral disease at the start. There was no sex disparity with regard to the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved an ASAS20 response (OR 0.63, 95% CI 0.37–1.07, p = 0.09). An inactive disease status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI 0.32–1.27, p = 0.22). These sex differences in response to TNFi were more pronounced in adjusted analyses (OR 0.34, 95% CI 0.16–0.71, p = 0.005 for ASAS20 and OR 0.10, 95% CI 0.03–0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all the other outcomes assessed.Conclusion.In AS, fewer women respond to TNFi and women show a reduced response in comparison to men.

Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA. Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months). Patients were categorized according to BMI: normal (BMI 18.5 to <25), overweight (BMI 25–30), and obese (BMI >30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued the TNFi were considered nonresponders. We controlled for age, sex, HLA-B27, axSpA type, BASDAI, BASMI, elevated C-reactive protein (CRP), current smoking, enthesitis, physical exercise, and co-medication with disease-modifying antirheumatic drugs, as well as with nonsteroidal anti-inflammatory drugs in multiple adjusted logistic regression analyses. A total of 624 axSpA patients starting a first TNFi were considered in the current study (332 patients of normal weight, 204 patients with overweight, and 88 obese patients). Obese individuals were older, had higher BASDAI levels, and had a more important impairment of physical function in comparison to patients of normal weight, while ASDAS and CRP levels were comparable between the three BMI groups. An ASAS40 response was reached by 44%, 34%, and 29% of patients of normal weight, overweight, and obesity, respectively (overall p= 0.02). Significantly lower odds ratios (ORs) for achieving ASAS40 response were found in adjusted analyses in obese patients versus patients with normal BMI (OR 0.27, 95% confidence interval (CI) 0.09–0.70). The respective adjusted ASAS40 OR in overweight versus normal weight patients was 0.62 (95% CI 0.24–1.14). Comparable results were found for the other outcomes assessed. Obesity is associated with significantly lower response rates to TNFi in patients with axSpA.

With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. Patients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment. Among 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p= 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p= 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n= 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p= 0.01). The effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR.

Objective.To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers.Methods.We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort.Results.All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0).Conclusion.With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

Dieser Artikel soll den aktuellen Stand des Wissens über Viskosupplementation bei der Behandlung der Arthrose zusammenfassen. Es wird die Wirkungsweise der Hyaluronsäure-Derivate auf mechanischer, biochemischer und zellulärer Ebene skizziert. Da die exogen eingeführten Hyaluronsäure-Derivate durchschnittlich nur 10 bis 20 Stunden in der Synovialflüssigkeit nachzuweisen sind, ihre Wirkung aber über Monate hinaus anhält, wird eine indirekte, multifaktorielle Wirkung postuliert: Modulation der Aktivität der verschiedenen, in der Entwicklung und Progression der Arthrose involvierten Zellen (Synovialzellen, Chondrozyten, entzündungsvermittelnden Zellen) wahrscheinlich durch direkte Wirkung an deren spezifischen Rezeptoren. Diese Rezeptoren spielen eine wichtige Rolle in der Migration, Adhäsion und Aktivierung von entzündungsvermittelnden Zellen sowie in der Reifung und Differenzierung der Chondrozyten zur Synthese der Knorpelmatrix. In verschiedenen experimentellen Studien in vitro und in vivo wurden eine schmerz- und entzündungshemmende Wirkung dieser Präparate nachgewiesen. Diese Resultate wurden teilweise in der Klinik bestätigt. Klinische Studien zeigten, dass eine Verbesserung der Symptome und möglicherweise eine Verzögerung der Progression der Krankheit erzielt werden kann. Wichtig ist auch zu betonen, dass diese Therapie gut toleriert wird und komplikationsarm ist. Es braucht noch weitere Studien, um die optimale Dosierung, das bestgeeignete Produkt (nieder- oder hochmolekulares Präparat) und die möglichen Kombinationen mit anderen Therapien festzulegen sowie die Wirkung in den verschiedenen Populations-Subtypen zu evaluieren.

In rats with adjuvant arthritis, an analysis was made of the metabolism of sulfated proteoglycans, with particular attention to the dorsal skin and the extremities. Alterations were demonstrated in all the tissues examined. In the uninflamed dorsal skin, the uptake of exogenous sulfate was diminished. By contrast, in both hind limbs, at the injected and the non-injected site, the turnover of sulfated mucopolysaccharides was increased, above all in ligament and cartilage; the calcium content of the bone tissue of both hind legs was, however, not affected by the disease.

Das Ausmaß der saluretischen Wirkung eines Präparates steht nicht in direktem Zusammenhang mit seinem in vitro gemessenen Hemmeffekt gegenüber der Carboanhydratase.

Diese Arbeit befaßt sich mit der chemischen Analyse von 9 Aponeurosen mit Dupuytrenscher Kontraktur. Diese Analysen betreffen die Glucuronsäure (saure Polysaccharide), die Aldosen (Aldopolysaccharide), das Tyrosin und das Arginin (Index des Eiweißgehaltes), das Oxyprolin (Kollagengehalt). Die Resultate werden mit Werten verglichen, welche durch chemische Analyse verschiedener Gewebe der Hand von Vergleichspersonen (Beugesehnen, Lederhaut, Aponeurosis palmaris) erhalten wurden. Außerdem werden auch Daten einer anderen Arbeit über die Gerontologie von Bindegewebe verschiedener Natur zum Vergleich herangezogen.

Background: Sex differences with regard to clinical manifestations and response to tumor necrosis factor inhibitors (TNFi) have been delineated for the radiographic form of axial spondyloarthritis (axSpA). More limited evidence for a differential effectiveness of treatment in genders exists for the nonradiographic disease state (nr-axSpA). The aim of the study was to compare demographics, clinical parameters, and response to TNFi in women versus men with nr-axSpA. Methods: We compared disease characteristics of 264 women and 231 men with nr-axSpA at inclusion in the prospective Swiss Clinical Quality Management Cohort. Response to a first TNFi was assessed in 85 women and 78 men without diagnosed co-morbid fibromyalgia. The primary outcome was the proportion of patients achieving the 40% improvement in the Assessment of SpondyloArthritis international Society criteria (ASAS40) at 1 year. Additional response outcomes were evaluated as secondary outcomes. Patients having discontinued TNFi were considered non-responders. Logistic regression analyses were adjusted for baseline differences, which might potentially mediate the effect of sex on treatment response. Results: Compared to men, women had a longer diagnostic delay, a higher level of perceived disease activity, and more enthesitis and were in a lower percentage HLA-B27 positive. An ASAS40 response was achieved by 17% of women and 38% of men (OR 0.34; 95% CI 0.12, 0.93; p= 0.02). A significantly lower response rate in women was confirmed in the adjusted analysis (OR 0.19; 95% CI 0.05, 0.62; p= 0.009) as well as for the other outcomes assessed. Conclusion: Despite only few sex differences in patient characteristics in nr-axSpA, response rates to TNFi are significantly lower in women than in men.