Reducing Flares in Patients With Low Rheumatoid Arthritis Disease Activity
Clinical Study Title:
Flares in Rheumatoid Arthritis Patients With Low Disease Activity: Predictability and Association With Worse Clinical Outcomes
Clinical Study Abstract:
OBJECTIVE: To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes.
METHODS: Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion. At baseline and every 3 months, clinical (DAS28), functional [Health Assessment Questionnaire-Disability Index (HAQ-DI), EQ-5D, Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F), Medical Outcomes Study Short Form-36 (SF-36)], serum biomarkers [multibiomarker disease activity (MBDA) score, calprotectin, CXCL10], and imaging data were collected. Flare was defined as an increase in DAS28 compared with baseline of > 1.2, or > 0.6 if concurrent DAS28 ≥ 3.2. Cox regression analyses were used to identify baseline predictors of flare. Biomarkers were cross-sectionally correlated at time of flare. Linear regressions were performed to compare clinical outcomes after 1 year.
RESULTS: Of 152 patients, 46 (30%) experienced a flare. Functional disability at baseline was associated with flare: HAQ-DI had an unadjusted HR 1.82 (95% CI 1.20-2.72) and EQ-5D had HR 0.20 (95% CI 0.07-0.57). In multivariate analyses, only HAQ-DI remained a significant independent predictor of flare (HR 1.76, 95% CI 1.05-2.93). At time of flare, DAS28 and its components significantly correlated with MBDA and calprotectin, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers. Patients who flared had significantly worse outcomes at 12 months (HAQ-DI, EQ-5D, FACIT-F, SF-36, and radiographic progression).
CONCLUSION: Flares occur frequently in RA patients with LDA and are associated with worse disease activity, quality of life, and radiographic progression. Higher baseline HAQ-DI was modestly predictive of flare, while biomarker correlation at the time of flare suggests a noninflammatory component in a majority of events.
Bechman K, Tweehuysen L, Garrood T, et al. Flares in rheumatoid arthritis patients with low disease activity: predictability and association with worse clinical outcomes. J Rheumatol.2018;45(11):1515-1521.
Visiting Foreign Professor, Karolinska Institute
“The bottom line is that even patients with LDA need to be monitored by the rheumatologist frequently (eg, in my practice, every 3-4 months) to ensure that disease activity remains low and that they do not flare.”
We know that even in patients with RA with LDA, the disease has not completely gone away. We used to think that RA would “burn out” over time in cases of long-standing disease, but this is not the case. In fact, those patients with a 15- to 30-year history of RA still have clinical features of the disease. There may be systemic manifestations, such as anemia, fatigue, and depression, among others. So, when a patient has LDA, it does not mean that you can say, “Okay, I will see you in 2 years.” These patients still need to be monitored every 3 to 4 months.
Flares can manifest in a variety of ways as the immune system resets from a more normal homeostasis to an angry pattern of inflammation. The presentation will vary from patient to patient. For instance, some individuals may go to bed at night and wake up the next morning feeling as if they have been hit by a truck. A lack of sleep and fatigue may be predominant at first, but then, 1 or 2 days later, boom—they will notice that they are stiff and cannot button their shirt or fasten a bra. Other patients may have mild depression or mood swings, or may just not feel “right,” prior to experiencing an arthritis flare.
There are several things that we can do to prevent flares, including monitoring the patient’s C-reactive protein levels and sedimentation rate, as well as using tools such as the Vectra DA (a multibiomarker disease activity test) and ultrasound to measure disease activity. In particular, I want to make sure that the joints are not showing signals of activity, or Doppler signals, on ultrasound because such joints are more likely to flare. It is critical to see patients with LDA at least every 4 months because they will experience a reduced quality of life and worse structural damage if we do not keep them in LDA. There are also data showing that flares increase the risk for an adverse cardiovascular outcome. Every time there is a flare, it acts like a hit to the immune system that affects the cardiovascular system. This is important because cardiovascular disease is the number 1 cause of death in patients with RA.
Thus, we want to prevent flares for a number of reasons, and this study by Bechman et al reinforces that. Another finding from this study was that patients with LDA but high functional disability seem more likely to flare. These individuals may have many persisting pro-inflammatory cells that have already done significant structural damage, which puts them at risk of additional damage in the future. For example, a patient with LDA may have a functionally impaired hand from a past activity, and then in a flare it moves over to the other hand, the shoulder, or the knee. So, the bottom line is that even patients with LDA need to be monitored by the rheumatologist frequently (eg, in my practice, every 3-4 months) to ensure that disease activity remains low and that they do not flare.
Bechman K, Tweehuysen L, Garrood T, et al. Flares in rheumatoid arthritis patients with low disease activity: predictability and association with worse clinical outcomes. J Rheumatol. 2018;45(11):1515-1521.