CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.
One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).
Patrice Wendling/IMNG Medical Media
Dr. Sergio Schwartzman
The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).
Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.
"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.
One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.
Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).
The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.
Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.
Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.
"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.
Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."
He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"
Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.
Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.