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Can tight control of early RA with a DAS target yield significantly better outcomes?

ACR special Report

With the ongoing addition of the new therapies to our armamentarium, there has been much discussion of what the goals of therapy in rheumatoid arthritis (RA) should be: no evidence of disease (NED), specific targets (and if so, what targets), or a continuation of the best for the individual patient without specific targets. At the recent American College of Rheumatology scientific sessions, the case for targets was made by Duncan Porter, MD, in his report on the TACORA (Tight Control of Rheumatoid Arthritis) study[1]. In a new approach at the plenary sessions, commentary on the study was provided by James O'Dell, MD.

Dr. Porter pointed out the similarities between RA and diabetes, i.e. that both are chronic disorders in which serious complications develop over the course of a lifetime, often yielding serious morbidity and premature death. In diabetes, tight glycemic control - linked to specific HbA1c targets - has been proven to reduce the risk of serious complications.

TACORA sought to determine whether tight control of early RA - with a target of a Disease Activity Score (DAS) of <2.4[2] -- could be achieved using an intensive treatment protocol to escalate standard DMARDs, and whether that tight control would result in significantly better outcomes.

The study randomized 110 patients with active RA of less than 5 years duration to routine or intensive outpatient care for 18 months. "Intensive care" consisted of monthly outpatient assessments; objective assessment of disease activity; intra-articular corticosteroid injections; and the targeting of persistent disease activity using a protocol to escalate DMARD therapy in patients with a disease activity score >2.4. Therapy began with sulfasalazine monotherapy; if the target was not achieved, triple therapy was instituted; if the target was still not achieved, doses were escalated to maximum; if necessary, oral prednisolone was added, a switch to MTX/cyclosporin was made, or an alternative DMARD was substituted. Anti-TNF agents were not used.

Although the treating physicians, obviously, were not blinded, an evaluator blinded to treatment assessed disease activity, quality of life and physical function, and radiographs were scored using the modified Sharp score.

As would be expected, more aggressive therapy led to improvements in HAQ and in quality of life scores, and decreased erosion. The intensive group achieved a DAS of 1.4, compared to a 2.7 in the routine group; 67% of patients in the intensive group achieved ACR70, compared to 18% of the routine group. The HAQ scores were striking at -0.97 in the intensive group and 0.47 in the routine group. (Interestingly, adverse events were less frequent in the intensive group than in the routine group.) It is not known how the use of anti-TNF agents might have altered the results of this trial, as they might have led to further improved outcomes in both the routine and intensively treated patients.

The authors concluded that "patients with early RA should be treated intensively using standard DMARDs according to a protocol that targets persistent disease activity." Thus, this study joins many that support aggressive early treatment of RA. As Dr. O'Dell noted in his commentary, European rheumatologists use handheld DAS calculators which allow point-of-care calculation of scores, which involve tender joint count, swollen joint count, ESR, and the patient's general health status as assessed by the patient using a 100-mm visual analog scale. Instant DAS calculators can also now be found on the Internet[3].

Aiming for a DAS <2.0 led to superior outcomes but does not define the limits beyond which risk/benefit no longer favors treatment escalation. The goal of no evidence of disease (NED) in the treatment of RA has been put forth by some, and the risk/benefit of continued escalation until NED is reached requires further study.

As Dr. O'Dell noted in his commentary, it is difficult to generalize regarding the target in the individual case, especially in view of the variability in medication tolerance between patients. For the moment, the message of this article is that we should be more rather than less aggressive in the individual case, but individualization is still required. The case for pushing even further -- to NED in all patients with RA -- remains provocative, but requires significant further data before becoming our standard.

[1] Porter DR, Grigor C, Stirling A, Capell HA. A Randomised Controlled Trial of a Strategy of Tight Control of Disease Activity in Rheumatoid Arthritis- outcome Over 18 Months. Arthritis Rheum. 2003 Sep;48(9):S232. (Abstract #515)

[2] "5.1 indicates high disease activity; a score <3.2 indicates low disease activity; and a score <2.6 indicates the patient is in remission." http://www.rheumatologycme.org

[3] See footnote 2 for 2 resources for online DAS calculator


Headshot of Theodore R. Fields, MD, FACP
Theodore R. Fields, MD, FACP
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

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