Methods
With the approval of the EULAR Executive Committee, the convenor (JSS) and epidemiologist (RL) who led the 2010 activity formed a Steering Group and a Task Force with the aim of updating the 2010 EULAR recommendations for the management of RA.
Task Force
Comprised of 33 members from 11 European countries and the USA, this EULAR Task Force included four patient representatives, 24 rheumatologists, an infectious disease specialist, a health economist and three fellows; care was taken to have a good representation of clinicians and experts experienced in RA clinical trials and their analysis from all European regions.
Initially, a Steering Group prioritised research questions and search terms for the three SLRs. These searches expanded and updated the available published information on efficacy of csDMARDs (as monotherapy or combination therapy, with and without glucocorticoids), efficacy of bDMARDs (as monotherapy or combined with csDMARDs) and safety aspects of csDMARDs and bDMARDs; treatment strategies were contained in the present SLRs rather than being separate as in 2010. Although the SLRs informing the 2010 EULAR recommendations also included a search on economic evaluations, the Steering Group felt that re-evaluation was not necessary because the approval status and price of new agents such as bsDMARDs was unknown.
Subsequently, with the help of their mentors, the three fellows performed the respective SLRs using established databases, including registry data for safety outcomes, and abstracts, especially from recent meetings (American College of Rheumatology 2012, EULAR 2012 and 2013). Details on and results of the SLRs are reported separately. Levels of evidence and grades of recommendation were determined according to the standards of the Oxford Centre for Evidence-Based Medicine.
Consensus Finding
At a subsequent meeting, these data were presented first to the Steering Group consisting of nine rheumatologists, an infectious disease specialist and a patient representative, who drafted a preliminary set of new recommendations based on their discussions. The search results as well as the drafted proposal for the recommendations were subsequently presented to the whole Task Force and discussed in detail in four break-out groups focusing on (i) csDMARDs and tsDMARDs, (ii) glucocorticoids, (iii) bDMARDs and (iv) safety aspects. After these deliberations, each subgroup reported their respective results and made new proposals for the recommendations to the entire group. After discussion, the Task Force then amended them as deemed appropriate to achieve final consensus, ultimately voting on each individual recommendation. When an initial majority of 70% in favour of—or against—a recommendation or formulation was not achieved, the contents or wordings were amended until a majority of the Task Force members approved the individual item. The results of the final ballot are presented for each of the recommendations as a percentage of voting members. An ultimate round of wording refinements was carried out via electronic communication but with no changes of the meaning permitted. This was accompanied by anonymous voting on the strength of recommendation (level of agreement) for each item on a 0–10 scale (0, no agreement at all; 10, full agreement).
A few principal considerations had already been developed by the Steering Group before the SLRs and were subsequently approved by the whole Task Force: (i) all of the 2010 recommendations should be reconsidered on the basis of new available supportive or contradicting evidence and voted upon; (ii) any of the previous recommendations could be kept as had been formulated, could undergo textual amendments, could be totally abandoned or could be shifted from a prominent place in the table listing the individual recommendations to the text accompanying them; (iii) although not yet approved and used in clinical practice outside the USA at the start of the current activity, it was deemed important to at least discuss and possibly formulate a recommendation on the application of tofacitinib based on the evidence from the literature; (iv) while not yet approved or used in practice in Europe or North America, it was also deemed important to at least discuss and potentially express a view on the place of biosimilars in the therapeutic arena based on available evidence.
In line with these a priori considerations and the potential need to provide some totally new recommendations, each of the three overarching principles and 15 recommendations of the consensus published in 2010 underwent thorough re-evaluation for their validity based on information that had become available from trials and registries during the years since the last SLR and consensus finding; where no new evidence had been found, the evidence from the 2010 searches was applied.