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WASHINGTON -- Rheumatoid arthritis (RA) patients who achieved sustained remission had better long-term outcomes than those with lingering low-level symptoms, a single-center study found -- casting doubt on current guidelines that say low disease activity (LDA) is an acceptable target for management.

Patient-reported outcomes tracked for 2 years all pointed to worse pain and fatigue, greater use of assistive devices, and numerically higher rates of surgery for patients with sustained LDA, relative to those in full remission, reported Michael Weinblatt, MD, of Brigham & Women's Hospital in Boston.

For many outcomes, the differences were dramatic, Weinblatt's presentation at the American College of Rheumatology (ACR) annual meeting showed.

In the study of 200 RA patients enrolled in the so-called at Brigham & Women's Hospital, disease activity was categorized into three groups of Clinical Disease Activity Index (CDAI) scores: remission (<2.8), very (V)LDA (2.8 to ≤6), and LDA (>6 to 10). Outcomes included Multidimensional Health Assessment Questionnaire (MDHAQ) scores for pain, fatigue, and overall; use of durable medical equipment (DME) such as canes, wheelchairs, or special tubs; and RA-related and RA-unrelated surgery.

Weinblatt reported the following average rates at year 2 for the three groups:

• MDHAQ pain: remission, 7.2; VLDA, 21.2; LDA, 37.4
• MDHAQ fatigue: remission, 18.0; VLDA, 35.2; LDA, 44.0
• MDHAQ overall: remission, 0.09; VLDA, 0.29; LDA, 0.43
• DME use: remission, 9%; VLDA, 19%; LDA, 40.6%
• Surgery (both types combined): remission, 14.6%; VLDA, 29.1%; LDA, 31.3%

P values for the differences between remission and LDA were <0.001 for all but the last, which fell short of significance. Also, the differences were attenuated somewhat when the data were adjusted for age, sex, disease duration, comorbidity burden, and baseline MDHAQ score. Still, the stepwise worsening of outcomes with increasing disease activity remained apparent.

Weinblatt offered two main conclusions from the findings: one, that "new effective drug, treatment strategies, and policies that help patients with RA achieve remission or VLDA offer the potential to reduce functional disability and associated economic burden to the healthcare system."

And two, rheumatology leaders should take a harder look at practice guidelines that allow LDA as a treat-to-target goal. Weinblatt said he'd served on the ACR committee that compiled the group's on RA, from 2021. "We wrote that we strive for remission, but realize it's a very difficult task and going to low disease activity would be an appropriate goal."

Indeed, the ACR guideline states, "A minimal initial treatment goal of low disease activity is conditionally recommended over a goal of remission." Meanwhile, from the ACR's trans-Atlantic counterpart, the European Alliance of Associations for Rheumatology, calls for "attainment of the main treatment target, which is remission in early and low disease activity in long-standing disease, at about 6 months."

Now, the current study -- though not large and from a single center -- highlights the tradeoff that clinicians and patients face when settling for LDA.

Weinblatt cautioned that "this is obviously data from one dataset; I would encourage those of you with large registries to go back and look at your datasets to see if our findings are confirmed."

"If they are confirmed, it suggests to me that we need to modify the definition of LDA; that perhaps 6 to 9 [in CDAI score] is not satisfactory as a goal in rheumatoid arthritis," he said, adding that it's imperative to examine this question more broadly.

Study Details

Overall, the BRASS registry currently follows almost 1,600 patients. For the new analysis, Weinblatt and colleagues picked out those whose records indicated a full year of achieving sustained remission or LDA, collectively defined as CDAI ≤10, and who had an additional year in which this level of disease activity was maintained. Exactly 200 patients qualified for inclusion.

Mean patient ages were in the 50-55 range for the three disease activity groups. About 80% were women, and close to 95% were white. Roughly half were positive for RA-related autoantibodies; this did not vary markedly between groups.

At year 1, 45% of this group were in CDAI remission (and 43% of this group attained remission during year 1 of follow-up); 40% were in VLDA, and 16% in LDA.

Examining patients' characteristics at baseline, it was evident that those who ended year 1 at VLDA/LDA were more overweight, showed higher C-reactive protein levels, had lived with RA longer, and had more symptomatic joints at baseline, relative to those achieving remission. Their MDHAQ scores were also higher at baseline, and they were already more likely to be using DME.

One audience member asked Weinblatt whether he thought the treat-to-target approach needs more than two endpoints: meeting or not meeting the target. What's the value in keeping multiple possible targets to aim at?

Weinblatt replied that it's a thorny question, now that physicians are often "scrutinized" and "audited" for patient outcomes. "The question is, what's the target? If it's remission, which is our goal, I'd argue that most of us do not achieve that in the majority of our patients." With the metrics now used to evaluate care quality, most rheumatologists would be seen as consistently failing, Weinblatt pointed out, potentially with undeservedly harsh consequences.

"If all of our drugs achieved remission, I wouldn't be giving this abstract today," Weinblatt continued. "Remission is still a very difficult target for many of our patients."

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