Concerns linger for ‘problematic’ 2021 ACR RA guidelines
Click Here to Manage Email Alerts
While the 2021 American College of Rheumatology rheumatoid arthritis recommendations improved over the 2015 document, understanding the weaknesses and limitations of the most recent iteration can be beneficial, according to a presenter here.
Roy M. Fleischmann, MD, clinical professor at the University of Texas Southwestern Medical Center and in private practice at Rheumatology Associates in Dallas, Texas, acknowledged that there were positives to the most recent set of recommendations. One was that the whole format was changed to highlight commonly encountered clinical scenarios. “It was actually quite an improvement,” he said.
The diversity of the panel and the inclusion of the patient voice were also “valid and valuable,” he added.
That said, Fleischman did have some concerns with the core leadership team that developed the Population, Intervention, Comparator, Outcome (PICO) questions, the review team and the voting panel. He noted that many members of these teams were academicians who were not directly involved with patient care on a daily basis. “That raises a question as to whether or not this group are all truly expert,” he said. “The result is recommendations that may be problematic.”
An additional concern for Fleischmann pertains to the 81 recommendations that ultimately made it into the document. “None of the recommendations were made on a high level of evidence,” he said, noting that six recommendations were based on a moderate level of evidence and 75 were based on low levels of evidence.
Methotrexate was at the center of some of the specific recommendations that Fleischmann found questionable. For example, methotrexate monotherapy is strongly recommended over a biologic or targeted synthetic disease-modifying anti-rheumatic drug (DMARD) monotherapy and over a tumor necrosis factor (TNF) inhibitor in the first line.
“But what is the evidence?” he said. Findings from the EARLY-RA trial showed that tofacitinib “beat methotrexate unconditionally.”
Further data have shown that the interleukin (IL)-6 inhibitor tocilizumab (Actemra, Genentech) monotherapy has also bested methotrexate in various clinical parameters.
“How could methotrexate be favored over a targeted synthetic DMARD or an IL-6 inhibitor if the evidence is otherwise?” Fleischmann said.
Fleischmann raised the argument that although methotrexate continues to be the anchor drug in RA, “due to cost, efficacy in 30% of patients, and importance in combination with biologic DMARDs,” there is evidence suggesting that other drugs may be more effective.
In addition, Fleischmann suggested that there is “zero evidence” suggesting that subcutaneous formulations of methotrexate are as effective as oral formulations. “Does anyone know of a trial where subcutaneous methotrexate beats oral clinically?” he said. “I don’t.”
Fleischmann summed up his over-arching concern with the use of evidence in the development of the document. “They missed important manuscripts,” he said. “Important manuscripts did not quite fit their criteria, so they skipped them.”
Moving beyond drug choices, another area of concern for Fleischmann is the move from remission to low disease activity as a treatment goal. He understands that the patient panel was instrumental in this development. “Patients said, ‘If you tell me I have to get into remission and I do not, it will be demoralizing,’” he said. “The panel went along with it.”
For Fleischmann, true remission yields not only benefits in RA disease activity, but in comorbidities like cardiovascular and pulmonary disease.
If there is a companion concern for Fleischmann, it is the measurements used to assess disease activity. While he believes that the clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are “quite” good, he suggested that the 28-joint disease activity score (DAS28) is “less than optimal.”
“There are several ways to measure disease activity endorsed by the ACR,” he said. “The ACR does a lot of good things but not this one. The SDAI, CDAI and DAS28(ESR) are reasonable. The DAS28(CRP) and especially RAPID3, overestimate response. The RAPID3, as a PRO, is helpful in conjunction with the CDAI, SDAI or DAS28(ESR).”
Collapse
Fleischmann RM. 2021 ACR Guidelines for the Treatment of RA: What is missing and what can be improved? Presented at: Congress of Clinical Rheumatology-West annual symposium; September 18-21, 2021 (hybrid meeting).
Click Here to Manage Email Alerts