Welcome to the Rheumatology Resource Centre.
The Rheumatology Resource Centre is hosted by the journal Best Practice and Research Clinical Rheumatology. It aims to provide healthcare professionals with educational resources and the latest peer-reviewed research on rheumatoid arthritis. Funded by an educational grant, the Rheumatology Resource Centre is freely available. Content is selected by the editorial board; Dr. Thasia Woodworth, Dr. Sarah Mackie and Prof. Tony Woolf.
Healthcare professionals, will have access to articles and videos covering key topics in rheumatoid arthritis, focusing on targeted therapies, including the role of the IL-6 pathway in inflammation, as well as best practices in early diagnosis, treatment and patient care.
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Karine Briot, Christian RouxSummary Glucocorticoids are effectively used in the management of inflammatory diseases but their use is associated with significant morbidity. Glucocorticoid-induced...
Commentary by Sarah Mackie on GIOP
In this interview Professor Ken Saag discusses the development and presentation of the new American College of Rheumatology (ACR) guidelines on glucocorticoid-induced osteoporosis (GIOP). One of the key messages to emerge from this video is the huge collaborative effort that was involved in producing these guidelines and the efforts that were made to consider the way the guideline would ultimately be used.
The modern discipline of guideline development methodology evolved from two separate traditions: the process of the traditional consensus conference, and the quantitative methods of clinical epidemiology, which produced the discipline of evidence-based medicine (interested readers might wish to refer to the recent book by Miriam Solomon, Making Medical Knowledge http://newbooksnetwork.com/miriam-solomon-making-medical-knowledge-oxford-2015/). Since then the guideline development methodology has taken on board wider societal and cultural shifts as it has become clear that in the real world the pathway of moving from evidence to recommendations is not always as straightforward as one might hope. Like the British Society for Rheumatology (BSR) and many other learned societies in other clinical disciplines, the ACR now fully endorses the GRADE methodology of guideline development [http://gradeworkinggroup.org]. The first example of ACR guidelines to use GRADE from start to finish was the 2015 ACR/EULAR guidelines for treatment of polymyalgia rheumatica (PMR) [http://ard.bmj.com/content/74/10/1799.full]. There is recognition that there are different domains of “expertise” and that guideline panels benefit from diversity of expertise. Both the PMR and the GIOP guideline panel included not only specialists in the field but also generalists and also, importantly, patients.
The GRADE process starts with a stakeholder consultation in order to identify the critical outcomes driving the structured clinical questions that then become the focus for the systematic literature review. This literature review, as is evident from the interview with Professor Saag, must be done thoroughly and is a huge piece of work. GRADE attempts to streamline this as far as possible by means of a structured review of each publication for all relevant outcomes. The traditional “evidence pyramid”, with its strict "hierarchy of evidence” or “levels of evidence" in which trials always outrank observational studies, has developed into a somewhat more nuanced approach in which the strength of evidence depends not only on the nature of that evidence but also on its quality with regard to that particular clinical question. This requires considerable skill in critical appraisal, going far beyond simply using evidence-based medicine as a “cookbook” or algorithm for producing a guideline. The quality of evidence is then graded - for example as high, moderate, low or very low.
Following the literature review the recommendations are debated by the panel; here the collective expertise of the panel comes into play, for example in recognising that glucocorticoids and inflammation can both cause bone loss; these mechanisms interact at multiple levels including the 11beta-hydroxysteroid dehydrogenase type 1 enzyme system [Briot and Roux, RMD Open 2015]. Hard choices have to be made about how to incorporate considerations of resource use and stakeholder values and preferences. GRADE encourages a focus on important clinical outcomes rather than surrogate endpoints, and on absolute risks/benefits rather than relative risks/benefits; hence the use of FRAX [https://www.shef.ac.uk/FRAX/tool.jsp], based on large-scale epidemiological data, acknowledging the multiple factors contributing to fracture. Again here we see the value of observational studies and real-world effectiveness data, as well as trials-based efficacy data. In a guideline intended to be applied across diverse clinical settings, within a pluralistic healthcare system, it can be difficult to generalise. A great virtue of GRADE is that these considerations are made explicitly and there is transparency in reporting the justifications.
Finally Professor Saag discusses some of the challenges faced by guideline developers. One of the major challenges is the imperfect nature of the evidence base: when one comes to look hard at it, there is never quite as much evidence for real-world practice as one would like. Judgement is needed about the extent to which data from other indications (for example, post-menopausal osteoporosis or male osteoporosis) can be applied.
Is all this effort worth it? The indication is that the new GIOP guidelines were very well-received at ACR. They are pragmatic and user-friendly while acknowledging the uncertainty inherent in the available evidence. After all, the guideline is produced not for the journals, but for the users: the clinicians and patients who are faced with everyday clinical dilemmas and wishing to make decisions informed by evidence. Other stakeholders including industry and payers will be watching these developments with interest and no doubt we will see parallel efforts in other areas of rheumatology.
Disclosure: Sarah Mackie participated in the guideline development group for polymyalgia rheumatica and is currently participating in the production of the updated BSR guidelines for giant cell arteritis, which is also using GRADE methodology.
American College of Rheumatology 2010 Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis
Jennifer M. Grossman, Rebecca Gordon, Veena K. Ranganath, Chad Deal, Liron Caplan, Weiling Chen, Jeffrey R. Curtis, Daniel E. Furst, Maureen Mcmahon, Nivedita M. Patkar, Elizabeth Volkmann, and Kenneth G. SaagArthritis Care & Research, Vol. 62, No. 11, November 2010, pp 1515-1526, DOI 10.1002/acr.20295 (c) 2010, American College of Rheumatology
Dual Cytokine Inhibition with ABT-122, a Tnf- and IL-17-Targeted Dual Variable Domain Immunoglobulin (DVD-Ig(tm)): Results from a 24-Week Open-Label Extension Study in Patients with Rheumatoid Arthritis [abstract]
Genovese MC, Weinblatt M, Mansikka HT, Peloso PM, Chen K, Li Y, Liu J, Padley RJ.Arthritis Rheumatol. 2016; 68 (suppl 10).
The Diagnostic and Predictive Value of Anti-Acetylated Peptide Antibodies in RA Patients Starting Methotrexate Treatment [abstract]
Studenic P, Blüml S, Bang H, Unger M, Raza K, Aletaha D, Smolen JS, Steiner G.Arthritis Rheumatol. 2016; 68 (suppl 10).
Clinical and Radiological Outcomes of 5 Years Remission Steered Treatment in Early Rheumatoid and Undifferentiated Arthritis Patients [abstract].
Akdemir G, Heimans L, Goekoop RJ, van Oosterhout M, Harbers JB, Bijkerk C, Steup-Beekman GM, Lard LR, de Sonnaville PBJ, Grillet BAM, Huizinga T, Allaart CF.Arthritis Rheumatol. 2016; 68 (suppl 10).