Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis

Aim: Physiotherapy is an integral part of the management of ankylosing spondylitis (AS) and there is a need for recommendations which focus on the rehabilitation of patients with AS. We aimed to develop recommendations for the physical therapy and rehabilitation of patients with AS based on the evidence and expertise. Methods: The Anatolian Group for the Assessment in Rheumatic Diseases (ANGARD) is a scientific group of Turkish academicians (physiatrists and rheumatologists) who are experts in the rehabilitation of patients with AS. A systematic literature search summarizing the current available physiotherapy and rehabilitation trials in AS were presented to the experts before a special 2‐day meeting. Experts attending this meeting first defined a framework based on the main principles and thereafter collectively constructed six major recommendations on physiotherapy and rehabilitation in AS. After the meeting an email survey was conducted to rate the strength of the recommendations. Results: Six key recommendations which cover the general principles of rehabilitation in AS in terms of early intervention, initial and follow‐up assessments and monitoring, contraindications and precautions, key advice for physiotherapy methods and exercise were constructed. Conclusion: These recommendations were developed using evidence‐based data and expert opinion. The implementation of these recommendations should encourage a more comprehensive and methodical approach in the rehabilitation of patients with AS. Regular lifelong exercise is the mainstay of rehabilitation and there is a considerable need for well‐designed studies which will enlighten the role of physical therapy in the management of AS.     

A survey of European and Canadian rheumatologists regarding the treatment of patients with ankylosing spondylitis and extra-articular manifestations

Ankylosing spondylitis (AS) is a disabling inflammatory disease accompanied by a variety of extra-articular manifestations in a significant number of patients. These manifestations, including Crohn’s disease, ulcerative colitis, psoriasis, and uveitis, share a similar inflammatory mechanism with one another and with AS. Extra-articular manifestations are observed in a larger percentage of patients with AS and spondyloarthritides (SpAs) than the normal population; therefore, it is important to identify these and other inflammatory-mediated conditions and consider them when treating SpAs. How rheumatologists approach patients with both AS and extra-articular manifestations may lead to a better understanding of what treatment approaches could be taken to optimize patient outcomes. Rheumatologists (N = 453) from five European countries and Canada who treat AS were surveyed to determine treatment practices and management of both AS and its associated extra-articular manifestations. Most rheumatologists (93%) believe AS could be diagnosed earlier as the average time between symptom onset and diagnosis was approximately 4 years. In total, 60% routinely screen patients with AS for extra-articular manifestations, although this varied considerably across countries. The majority (97%) agrees that controlling inflammation is critical during treatment, and patients with extra-articular manifestations tend to have poorer prognoses than those patients with only axial AS. Treatment considerations varied depending on whether patients presented with only axial AS or had extra-articular manifestations, where use of biologics became more common. Rheumatologists agree that patients with both AS and extra-articular manifestations require a different treatment strategy than patients with AS alone. Results of this survey highlight areas where rheumatologists differ in their clinical management of patients with AS including tools used for disease assessment and the routine screening, or lack thereof, for other inflammatory diseases. This evidence may suggest aspects within clinical practice where modifications may be made in order to optimize patient outcomes.     

Core set of recommendations for patients with ankylosing spondylitis concerning behaviour and environmental adaptations

Advice concerning behaviour and adaptations of living and working environment is considered an unmet need by patients with ankylosing spondylitis (AS). The aim of this study was to develop a core set of recommendations to be given to patients by their rheumatologists. A systematic literature research of scientific and patient-oriented literature revealed 70 raw recommendations. These recommendations were evaluated and ranked at a meeting of the Ankylosing Spondylitis International Federation (ASIF, 26 participants including 19 patients with AS, 5 rheumatologists and 2 physiotherapists from 13 countries) in November 2011. Thereafter, the 59 remaining recommendations were extensively discussed, supplemented, reworded, condensed and voted on during a meeting of local branch leaders of the AS patient organisation in Germany (Deutsche Vereinigung Morbus Bechterew, DVMB) with 80 participants (95 % of whom with AS), 2 rheumatologists and 1 occupational therapist in March 2012. The core set of final recommendations comprises (1) a general statement regarding living with AS which was considered highly important by patients and (2) the following domains: sitting position, walking, sleeping, at work, exercises, sports and recreational activities, diet and lifestyle, sexuality and pregnancy, fall prevention, car driving and advantages of membership in an AS-specific patient organisation. Most recommendations are relevant already in early disease, others concern advanced AS (e.g. fall prevention and car driving). The selected recommendations received high agreements (80–100 %). A first core set of recommendations for the behaviour and environmental adaptations of patients with AS was established under participation of many patients.     

Empfehlungen für die Behandlung der ankylosierenden Spondylitis gemäß ASAS/EULAR

The ASAS/EULAR recommendations for the management of ankylosing spondylitis have been updated in 2010. The recommendations have been extended from 10 to 11 recommendations and 4 superior principles have been introduced based on the level of evidence and expert knowledge. The recommendations have been translated into German and have been evaluated by 25 experts from Germany, Austria and Switzerland. The experts scored the strength of the recommendations (SOR) on an 11 point numerical rating scale (from 0?=?no agreement to 10?=?total agreement). With a mean score of 9.6?±?1.05 the SOR was generally very good.     

Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications

Ankylosing spondylitis (AS) is the most frequent and most severe subtype of spondyloarthritis and can be an outcome of any of the other spondyloarthritis subtypes. It primarily affects the axial joints, most notably the sacroiliac joints. Other sites of involvement include the spine, peripheral joints, and entheses (capsules, ligaments, and tendons). Inflammatory enthesopathy progressing to ossification and ankylosis is the pathologic basis for the disease. Extra-articular manifestations vary widely in terms of both frequency and severity. The most common extra-articular manifestations are represented by uveitis, bowel disease, heart, lung, skin, bone and kidney involvement. This review focuses on prevalence and clinical characteristics of the most common extra-articular manifestations in AS, and discuss the diagnosis and therapeutic difficulties that rheumatologists faces when dealing with such manifestations. The advantages of treatment with non-steroidal anti-inflammatory drugs (NSAIDs), especially if continuous use is envisaged, should be weighted against possible gastrointestinal and cardiovascular disadvantages. In the presence of history of gastrointestinal complaints or a high cardiovascular risk, NSAIDs should be used with caution. TNF inhibition has demonstrated effectiveness in the treatment of AS symptoms and all currently available anti-TNF agents appear to have similar efficacy. However, the efficacy of anti-TNF agents varies in the presence of extra-articular manifestations. Etanercept appears to have very little effect on inflammatory bowel disease and limited efficacy on the course of uveitis probably inferior to the monoclonal antibodies infliximab and adalimumab.     

Executive summary and recommendations from the WHO/UNAIDS/IAVI expert group consultation on 'Phase IIB-TOC trials as a novel strategy for evaluation of preventive HIV vaccines', 31 January-2 February 2006, IAVI, New York, USA

This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process.     

Atherosclerosis and endothelial dysfunction in patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease characterized primarily by axial joint involvement, sacroiliitis and various extra-articular manifestations. High cardiovascular mortality in AS has led many researchers to investigate possible risk factors involved with cardiovascular disease in these patients. This review summarizes published data concerning endothelial dysfunction and atherosclerosis in patients with AS. The author discusses current limitations and problems related to a better assessment of these two possible changes in AS.     

EULAR-Empfehlungen für die Schulung von Patienten mit entzündlich-rheumatischen Gelenkerkrankungen

In 2015 EULAR published recommendations for patient education of people with inflammatory arthritis. The recommendations included two superior principles and eight recommendations based on the level of evidence and expert knowledge. The German translation of the recommendations was evaluated by 15 German experts. Experts graded the strength of the recommendations (SOR) on an 11 point numerical rating scale (from 0 = no agreement to 10 = total agreement). The mean score was 8,8 ± 0,49.     

Evidence‐based recommendations for the monitoring and treatment of ankylosing spondylitis: results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64–100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.     

Ankylosing spondylitis in rheumatology patients in Ouagadougou (Burkina Faso)

The aim of this work was to study ankylosing spondylitis (AS) prevalence and its clinical, radiological and genetic features in Ouagadougou. This was a cross-sectional study over two first years of rheumatologic practice (March 2006 to March 2008). All the patients having AS met the modified criteria of New York. HIV serology was negative. Thirteen cases of AS (0.9%) with 11 men were diagnosed among 1,439 rheumatologic patients. The average age of the patients at the beginning of the disease was 27.1?±?11.5 years. Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index mean scores were, respectively, 47.8/100 and 44.46/100. No patient had presented extra-articular manifestations. Four (31%) patients had hip joint involvement. HLA B 27, among 11 patients, was positive in six (55%). Semiological features of AS among patients seen in Ouagadougou were similar to those of white race. HLA B27 prevalence in AS patients of Burkina Faso was similar to those of Afro-Americans.     

Kernsatz von Verhaltensempfehlungen für Patienten mit ankylosierender Spondylitis

Objectives

Patients with ankylosing spondylitis (AS) can contribute to a favorable disease course by their own behaviour and environmental adaptations. However, no standardized consensus recommendations on patient behavior and adaptations exist, neither internationally nor nationally. The aim of this study was to establish a core set of recommendations concerning favorable patient behavior to be given to patients with AS by rheumatologists.

Methods

An extended literature research in the scientific and patient-oriented literature revealed 70 recommendations. These recommendations were evaluated and ranked by importance at a meeting of the Ankylosing Spondylitis International Federation (ASIF, 26 participants from 13 countries) in November 2011. The remaining 59 recommendations were extensively discussed, supplemented, partially reworded, condensed and those with the highest priority were selected by consensus at a seminar of local branch leaders of the AS patient organization in Germany (Deutsche Vereinigung Morbus Bechterew) in March 2012 (80 participants, 95?% patients with AS).

Results

The core set encompasses 1) a general statement on living with AS and 2) recommendations in the areas of sitting position, walking, sleeping, at work, exercising, sports and recreational activities, diet and life style, sexuality and pregnancy, fall prevention, car driving and membership in an AS-specific patient organization. The selected recommendations received agreement by 80–100?% of the patients. Some recommendations (e.g. fall prevention and car driving) are more relevant to patients with advanced and usually longstanding disease, i.e. with advanced ankylosis or osteoporosis.

Conclusions

For the first time a core set of recommendations for the behavior of patients with AS was created in collaboration with many persons affected by the disease. Patients with AS should receive these recommendations from their rheumatologists, ideally early in the disease course. The German version of this core set is presented in this article.     

Cardiovascular and Cerebrovascular Diseases in Ankylosing Spondylitis: Current Insights

Patients with ankylosing spondylitis (AS) suffer from an increased cardiovascular (CV) risk. The evidence for increased atherosclerotic disease is nowadays convincing, while the precise contribution of the so-called AS-specific (related) cardiac manifestations toward the increased CV risk still needs to be determined. Such studies should be performed in the near future, since they might have clinical consequences-for example, mandatory echocardiographic screening of AS patients. There appears to be a clear contribution of the "traditional" CV risk factors, as well as the underlying chronic inflammatory process, to the increased atherosclerotic risk in AS. Furthermore, there is accumulating evidence for an etiological role of inflammation in the AS-related cardiac manifestations. Nowadays, CV risk management appears necessary for AS patients, and this should consist of, on the one hand, assessment and treatment, if necessary, of the "traditional" CV risk factors, and, on the other hand, effective suppression of the inflammatory process.     

International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis

OBJECTIVE: To obtain an international consensus about the use of anti-tumour necrosis factor alpha (anti-TNF alpha) for treating patients with ankylosing spondylitis (AS). METHODS: These recommendations were developed by a review of published reports in combination with expert opinion, including a Delphi exercise, and a consensus meeting of the ASsessments in AS (ASAS) Working Group. RESULTS: The final consensus comprises the following requirements: (1) For the initiation of anti-TNF alpha therapy: (a) a diagnosis of definitive AS; (b) presence of active disease for at least four weeks as defined by both a sustained Bath AS Disease Activity Index (BASDAI) of at least 4 and an expert opinion based on clinical features, acute phase reactants, and imaging modalities; (c) presence of refractory disease defined by failure of at least two non-steroidal anti-inflammatory drugs during a single three month period, failure of intra-articular steroids if indicated, and failure of sulfasalazine in patients with peripheral arthritis; (d) application and implementation of the usual precautions and contraindications for biological therapy. (2) For the monitoring of anti-TNF alpha therapy: both the BASDAI and the ASAS core set for clinical practice should be followed regularly. (3) For the discontinuation of anti-TNF alpha therapy: in non-responders, consideration should be made after 6-12 weeks' treatment. Response is defined as improvement of (a) at least 50% or 2 units (on a 0-10 scale) of the BASDAI, (b) expert opinion that treatment should be continued. CONCLUSION: This consensus statement on anti-TNF alpha treatment in AS may be used for guidance in clinical decision making and as the basis for the development of guidelines. Evaluation of the healthcare consequences of this consensus is subject to further research by the ASAS group.     

International clinical guideline for the management of classical galactosemia: diagnosis,treatment, and follow-up

Classical galactosemia (CG) is an inborn error of galactose metabolism. Evidence-based guidelines for the treatment and follow-up of CG are currently lacking, and treatment and follow-up have been demonstrated to vary worldwide. To provide patients around the world the same state-of-the-art in care, members of The Galactosemia Network (GalNet) developed an evidence-based and internationally applicable guideline for the diagnosis, treatment, and follow-up of CG. The guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A systematic review of the literature was performed, after key questions were formulated during an initial GalNet meeting. The first author and one of the working group experts conducted data-extraction. All experts were involved in data-extraction. Quality of the body of evidence was evaluated and recommendations were formulated. Whenever possible recommendations were evidence-based, if not they were based on expert opinion. Consensus was reached by multiple conference calls, consensus rounds via e-mail and a final consensus meeting. Recommendations addressing diagnosis, dietary treatment, biochemical monitoring, and follow-up of clinical complications were formulated. For all recommendations but one, full consensus was reached. A 93 % consensus was reached on the recommendation addressing age at start of bone density screening. During the development of this guideline, gaps of knowledge were identified in most fields of interest, foremost in the fields of treatment and follow-up.     

Evaluation of the comorbidity burden in patients with ankylosing spondylitis using a large US administrative claims data set

Comorbidities among US patients with ankylosing spondylitis (AS) are inadequately understood. This study compared the prevalence and incidence of comorbidities between patients with AS and matched controls using national claims databases. Adults enrolled in the MarketScan Commercial and Medicare databases with ≥?1 inpatient or ≥?2 non-rule-out outpatient diagnoses of AS between January 1, 2012 and December 31, 2014 were included. Patients had to have ≥?1 AS diagnosis in 2013; the first AS diagnosis in 2013 was assigned as the index date. Control patients without AS were matched to AS patients on age, geographic region, index calendar year, and sex. Comorbidities were evaluated in AS patients and matched controls during the baseline and follow-up periods (before and after the index date, respectively). Hazard ratios of developing new comorbidities were estimated using Cox proportional hazard models adjusted for patients’ characteristics. A total of 6679 patients with AS were matched to 19,951 control patients. In addition to extra-articular manifestations of AS (inflammatory bowel disease [IBD], psoriasis, uveitis), a higher proportion of AS patients had asthma, cardiovascular disease, depression, dyslipidemia, gastrointestinal ulcers, malignancies, multiple sclerosis, osteoporosis, sleep apnea, and spinal fractures during the baseline period than matched controls. After AS diagnosis, a higher proportion of patients developed newly diagnosed cases of cardiovascular diseases, depression, osteoporosis, spinal fracture, IBD, psoriasis, and uveitis than matched controls. In this real-world, US claims-based study, patients with AS were shown to have significantly more comorbidities than matched controls.     

Atrial septostomy for pulmonary hypertension

Atrial septostomy represents an additional, promising strategy in the treatment of severe PPH. Experience with this procedure still is limited; however, based on analyses of the worldwide experience, several general conclusions and recommendations can be made. 1. Atrial septostomy can be performed successfully in selected patients with advanced pulmonary vascular disease. 2. Patients with primary pulmonary hypertension who have undergone successful AS have shown: a significant clinical improvement beneficial and long-lasting hemodynamic effects at rest a trend toward improved survival 3. The procedure-related mortality of the collective experience is high (16%). Several recommendations can be made to minimize the risk: [figure: see text] Atrial septostomy should be attempted only in institutions with an established track record in the treatment of advanced pulmonary hypertension, where septostomy is performed with low morbidity. Atrial septostomy should not be performed in patients in whom death is impending or who have severe right ventricular failure and are on maximal cardiorespiratory support. An mRAP greater than 20 mm Hg, PVR index greater than 55 u/m2, and a predicted 1-year survival less than 40% are significant predictors of procedure-related death. Before cardiac catheterization, patients should have an acceptable baseline systemic oxygen saturation (> 90% in room air) and optimized cardiac function (adequate right heart filling pressure, additional inotropic support if necessary). During cardiac catheterization, the following are mandatory: Supplemental oxygen Mild sedation to prevent anxiety Careful monitoring of variables (left atrial pressure, SaO2, and mRAP) Step by step procedure After AS, it is important to optimize oxygen delivery. Transfusion of packed red blood cells or erythropoietin (before and following the procedure, if needed) may be necessary to increase oxygen content. 4. Because the disease process in PPH is unaffected by the procedure (late deaths), the long-term effects of an AS must be considered to be palliative. 5. Despite its risk, AS may represent a viable alternative for selected patients with severe PPH. Indications for the procedure may include: Recurrent syncope or right ventricular failure, despite maximal medical therapy, including oral calcium-channel blockers or continuous intravenous prostacyclin (Fig. 11) As a bridge to transplantation When no other option exists.     

The "knowns" and "unknowns" of biologic therapy in ankylosing spondylitis

Since the first biologic agent was tested in the treatment of ankylosing spondylitis (AS), the ability of these therapies to dramatically improve the clinical symptoms and signs of the disease was very evident. Over the past decade, 4 tumor necrosis factor-alpha inhibitors have been approved by the Food and Drug Administration for the treatment of AS. Published data include randomized controlled trials, registries and observational studies. Guidelines have also been developed for the use of biologics in AS. Although a lot is known about the use of biologics in the AS, several "unknowns" remain. Whether these agents can alter the natural history of AS if started very early in the course or whether they can prevent extra-articular manifestations are among the important unanswered questions. Most of the data summarized in this review relate to tumor necrosis factor-alpha inhibitors, and other biologic agents that have been studied are included, as well. This review also summarizes what questions remain about the use of biologics in AS and what type of studies will be required to answer them.     

New onset of Crohn's disease during treatment of active ankylosing spondylitis with etanercept

We describe 3 AS patients treated with etanercept for active AS who developed new onset of CD while AS related symptoms responded well to etanercept. Typical symptoms of active CD occurred 11, 12, and 26 months after start of etanercept therapy, respectively. On colonoscopy, inflammatory lesions highly compatible with CD were found endoscopically and histologically in all patients. Etanercept was stopped, and CD responded well to standard treatment. One of the 3 patients was reexposed to etanercept later on. While the 2 patients without re-exposure to etanercept did not have further CD flares, the third patient flared 6 months after re-institution of etanercept in combination with azathioprine. New onset of CD may be considered as an immune-mediated injury induced by etanercept. Although this is an intriguing hypothesis, any causative role of etanercept remains unproven at this stage.