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recommendations specify the level of disease activity in the patient population (Table 1). However, evidence tables include pooled data from studies that often use different measures of disease activity; thus, specific definitions of low versus moderate-to-high disease activity are not provided for specific recommendations. Despite the large body of literature related to pharmacologic treatments for RA, the review team did not identify high-certainty evidence for many of the questions addressed. This discrepancy is due to the differences between clinically important PICO questions and the specific objectives of clinical trials. For example, few studies have examined how to best dose and administer methotrexate, the most effective and safe use of DMARDs in high-risk populations, and the risk–benefit tradeoffs associated with glucocorticoid use. Moreover, many trials could not be matched to specific PICO questions because of differences between the trials and the PICO questions’ specified study populations and treatment comparisons. Thus, many recommendations are based largely on very low-certainty or lowcertainty evidence. Incorporating medical evidence and expert input and consensus into clinical guidelines is core to the GRADE process and strengthens recommendations, particularly when there is limited evidence. Important gaps in knowledge are described in Table 7. In summary, this update includes recommendations related to initiation and adjustment of DMARD therapy in patients with RA. It also emphasizes the importance of minimizing use of glucocorticoids. It is expected that additional data may modify the direction and/or strength of specific recommendations. The ACR will update the recommendations and answer these and other questions as new data are published. ACKNOWLEDGMENTS We thank Stanley B. Cohen, MD, for his contributions during the scoping phase of the project. We thank Cassandra Calabrese, DO, Leonard Calabrese, DO, Joseph Lim, MD, Danielle Antin-Ozerkis, MD, Marcus R. Pereira, MD, MPH, Jason E. Stout, MD, MHS, and Kevin Winthrop, MD, MPH, for their expert input as the voting panel considered recommendations related to comorbidities. We thank Nancy Baker, ScD, MPH, OTR/I, and Daniel White, PT, ScD, MSc, for their contributions during the scoping phase of the project, as well as their input during early deliberations by the voting panel. We thank the patients who (along with authors Kristine Carandang, PhD, OTR/L, and Shilpa Venkatachalam, PhD) participated in the patient panel meeting: Susan Campbell, Rachelle Crow-Hercher, MEd, Doug Davis, Sidney Harper, Faith Powell, Zenethia Roberts, Mary Turner, and C. Whitney White, PharmD. We thank the ACR staff, including Regina Parker for assistance in organizing the face-to-face meeting and coordinating the administrative aspects of the project, Robin Lane for assistance in manuscript preparation, and Jocelyn Givens for assistance with recruitment for the patient panel. We thank Janet Waters and Janet Joyce for their assistance in developing the literature search strategy, as well as performing the initial literature search and update searches. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Fraenkel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Fraenkel, Bathon, England, St.Clair, Deane, Genovese, Kerr, Kremer, Sparks, Venkatachalam, Weinblatt, George, Johnson, Turner, Yaacoub, Akl. Acquisition of data. Fraenkel, Bathon, England, St.Clair, Carandang, Deane, Genovese, Kerr, Kremer, J. Singh, Sparks, Al-Gibbawi,
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