Developments in the scientific and clinical understanding of the spondyloarthritides

Major advances have been achieved over the last 10 years both in the clinical and scientific understanding of the spondyloarthritides (SpA), which can be separated in predominantly axial and predominantly peripheral SpA. The clinical progress includes the development of classification criteria, strategies for early diagnosis, definition of outcome criteria for clinical studies, and the conduction of a series of clinical studies with a focus on tumor necrosis factor (TNF) blockers. The proven high efficacy of TNF blocker treatment has meant a breakthrough for SpA patients, who until recently had only quite limited treatment options. More and more data have accumulated over recent years in regard to long-term efficacy and safety, prediction of response, and the relevance of extrarheumatic manifestations such as uveitis, psoriasis, and inflammatory bowel disease for treatment decisions with TNF blockers. A better understanding of the interaction of the immune system and inflammation with bone degradation/new bone formation is crucial for the development of optimal treatment strategies to prevent structural damage. Recent results from genetic studies could show that, besides HLA-B27, the interleukin-23 receptor and the ARTS1 enzyme are associated with ankylosing spondylitis. Only when the exact pathogenesis is clarified will a curative treatment be possible

Assessment of the microbial community in the cathode compartment of a plant microbial fuel cell

Introduction: In plant microbial fuel cells (plant-MFCs) living plants and microorganisms form an electrochemical unit able to produce clean and sustainable electricity from solar energy. It is reasonable to assume that besides the bacteria in the anode compartment also the cathode compartment plays a crucial role for a stable high current producing plant-MFC. In this study we aim to identify dominant bacterial species in the cathode compartment of the plant-MFC

Monopoly Distortions in Durability and Multi-Dimensional Quality

I show that Swan’s (1970) independence result requires a multiplicative interaction between durability and all other quality attributes. Because there is no compelling argument for a multiplicativity in quality, monopolists tend to distort durability, even with constant marginal costs. Distortions in durability and other quality aspects are aligned exactly when the marginal cost of quality do not increase too much with durability

Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis

Objective. To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). Methods. ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age 18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as 40% improvement from baseline (20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and 40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. Results. In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. Conclusion. Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases

Cost-effectiveness of etanercept in patients with severe ankylosing spondylitis in Germany

Objectives. To estimate the cost-effectiveness of etanercept (ETN) plus usual care (including NSAIDs) compared with usual care alone (including NSAIDs) in patients with severe AS in Germany. Methods. A mathematical model previously applied to the UK was adapted using resource use and cost data (for 2007) from the national database of the German Collaborative Arthritis Centres. Social health insurance (SHI) and societal perspectives were analysed. Assumptions on initial response and changes in health-related quality of life were based on Phase III randomized controlled trials. Initial treatment response according to British Society for Rheumatology guidelines were assumed as a conservative estimate in the German context. Long-term disease progression was based on the available literature. Incremental cost-effectiveness ratios (ICERs) were expressed as euros/quality-adjusted life year (QALY), for a cohort of 1000 patients over 25 years. Sensitivity analyses explored uncertainty in results. Results. In the base case, ETN plus usual care (including NSAIDs) yielded 1475 more QALYs at an additional cost of €80 827 668 (SHI) or €32 657 590 (societal) leading to an ICER of €54 815/QALY and €22 147/QALY, respectively. Over a shorter time horizon of 10 years, the ICERs were €59 006 and €29 815 for SHI and societal viewpoints, respectively. Assumptions having the largest impact on results included withdrawal rates from ETN, quality of life, disease costs and initial response. Conclusions. Cost-effectiveness for ETN in patients with severe AS in Germany differs according to the cost perspective. Study estimates were higher than in the UK but comparable with reported cost-effectiveness of anti-TNF treatments in patients with RA in German

Persistent clinical efficacy and safety of anti-tumour necrosis factor \textgreeka therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response

Background: There is insufficient evidence for the long-term efficacy and safety of anti-tumour necrosis factor therapy in patients with ankylosing spondylitis (AS). This is the first report on the treatment with infliximab over 5 years.Methods: As part of a multicentre randomised trial, 69 patients with active AS at baseline (BL) have been continuously treated with infliximab (5 mg/kg i.v. every 6 weeks)---except for a short discontinuation after 3 years (FU1). The primary outcome of this extension was remission according to the ASsessment in Ankylosing Spondylitis (ASAS) criteria at the end of year 5 of the study (FU2).Results: Of the 43 patients who completed year 3, 42 agreed to continue, 38 of which (90.5%) finished year 5 (55% of 69 initially). Partial clinical remission was achieved in 13 of 38 patients (34.2%) at FU1 and FU2. At FU2, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 2.5±1.9 (BL:6.4, FU1:2.5). BASDAI values <4 were seen in 79% of patients at both, FU1 and FU2. ASAS 20% and 40% responses were seen in 32 (84%) and 24 (63%) patients at FU2, respectively. Most patients classified as non-responders at FU2 were part-time responders, as all but one patient achieved an ASAS 20% response at least once within the last 2 years. Three types of responders were identified. No major side effects occurred during years 4 and 5 of infliximab therapy.Conclusions: Infliximab is safe and efficacious in AS patients over 5 years. The majority of the patients remained on treatment and had rather persistent levels of low disease activity. Different response types could be identified

results from the German Spondyloarthritis Inception Cohort

Background Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA. Methods In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0–4). The mean of two readers’ scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures. Results Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01–0.19) and the BASMI: b = 0.12 (95% CI 0.03–0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine. Conclusion Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity. Trial registration ClinicalTrials.gov, NCT01277419. Registered on 14 January 2011

Study protocol: Comparison of the effect of treatment with Nonsteroidal anti- inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti- tumour necrosis factor a therapy alone on progression of Structural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) – an open-label randomized controlled multicenter trial

Introduction There is some evidence that non-steroidal anti-inflammatory drugs (NSAIDs), in particular celecoxib, might possess not only a symptomatic efficacy but also disease-modifying properties in ankylosing spondylitis (AS), retarding the progression of structural damage in the spine if taken continuously. In contrast, this remains controversial for tumour necrosis factor alpha (TNF-α) inhibitors, despite their good clinical efficacy. The impact of a combined therapy (a TNF inhibitor plus an NSAID) on radiographic spinal progression in AS is unclear. Methods and analysis The aim of this study is to evaluate the impact of treatment with an NSAID (celecoxib) when added to a TNF inhibitor (golimumab) compared with TNF inhibitor (golimumab) alone on progression of structural damage in the spine over 2 years in patients with AS. The study consists of a 6-week screening period, a 12-week period (phase I: run-in phase) of treatment with golimumab for all subjects followed by a 96-week controlled treatment period (phase II: core phase) with golimumab plus celecoxib versus golimumab alone, and a safety follow-up period of 4 weeks. At week 108, the primary study endpoint radiographic spinal progression (as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score after 2 years) will be evaluated. Ethics and dissemination The study will be performed according to the principles of good clinical practice and the German drug law. The written approval of the independent ethics committee and of the German federal authority have been obtained. On study completion, results are expected to be published in a peer- reviewed journal. Trial registration number ClinicalTrials.gov register (NCT02758782) and European Union Clinical Trials Register (EudraCT No 2016-000615-33)