Dynamic Characteristics and Predictive Profile of Glucocorticoids Withdrawal in Rheumatoid Arthritis Patients Commencing Glucocorticoids with csDMARD: A Real-World Experience

Baseline Characteristics Between Discontinued and Continued Groups

As we previously presented, 124 out of 207 (59.9%) patients finally discontinued GC at the discretion of treating rheumatologist during a median (IQR) follow-up of 38.6 (20.7–60.3) months. For the 124 patients who discontinued GC, the median time (IQR) to GC cessation was 13.6 (8.0–24.6) months, ranging from 3.1 to 77.6 months. Compared with patients who discontinued GC, patients in the continued group were more frequently treated with concomitant NSAIDs (19.3 vs. 8.9%, p = 0.024) (Tables 1, 2, Supplementary Material Figure S1). Multivariate Cox analysis among age, disease activity, concomitant NSAIDs use, and initiating PSL dose revealed increasing age (HR 0.99, 95% CI 0.98–1.00, p = 0.043) and concomitant NSAIDs usage at GC initiation (HR 0.47, 95% CI 0.25–0.88, p = 0.018) were independent risk factors for of GC discontinuation failure (Table 2).

Table 1 Demographics and clinical characteristics between discontinued and continued groupsTable 2 Predictors for GC discontinuation by Cox multiple regression analysisChanges in PSL Daily Dose and Disease Activity Over Course Between Discontinued and Continued Groups

We further compared the changes in PSL dose and disease activity in the first 36 months after GC initiation between the discontinued and continued groups (Fig. 1). At baseline of GC initiation, the median PSL dose and disease activity were well balanced between the two groups. In general, the median PSL dose was significantly decreased with time in either the discontinued or continued group (p < 0.001) (Fig. 1A). Notably, the median PSL dose was significantly lower in the discontinued group than in the continued group as early as month 3 (p < 0.001). In relation to disease control, the median disease activity, measured by DAS28, SDAI, and CDAI, was markedly reduced in the first year and then fluctuated afterwards. Similarly, the median DAS28, SDAI, and CDAI in the discontinued group were significantly lower than that in the continued group at all follow-up time points, including as early as month 3 (Fig. 1B–D).

Fig. 1figure 1

Changes in prednisone dose and disease activity scores in discontinued and continued groups during the 36-month follow-up. DAS28-ESR disease activity score based on 28-joint count and ESR, SDAI simplified disease activity index, CDAI clinical disease activity index, PSL prednisolone

Change in Disease Activity at Month 3 and Subsequent GC Discontinuation

Considering sophisticated and dynamic aspects of GC discontinuation in real-world practice, we explored whether the reduction in disease activity at month 3 could predict subsequent GC discontinuation. Initially, all patients were divided into four groups according to the levels of disease activity change from baseline to month 3: worsening or no improvement (≤ 0%, group 1), slight improvement (0.1–24.9%, group 2), moderate improvement (25.0–49.9%, group 3) and substantial improvement (≥ 50.0%, group 4). Regarding CDAI, the likelihood of subsequent discontinuation of GC was increased by 48% with increasing one degree of improvement at month 3 (e.g., group 3 vs. group 2) (Table 3). After adjustment for age, baseline DAS, initial PSL dose, NSAIDs use, and PSL dose reduction at month 3, 47% increased likelihood of GC discontinuation was detected with one degree increases of CDAI improvement and patients in group 2, 3 and 4 had 1.77, 1.98 and 3.23 times more likely to discontinue GC respectively, compared with patients in group 1 (p for trend < 0.001). Similar findings were detected in both SDAI and DAS28 changes at month 3 (Table 3).

Table 3 Association of disease activity score changes at 3 months with subsequent GC discontinuationChange in Disease Activity at Week 6 and Subsequent GC Discontinuation

Of 130 patients with DAS changes document at week 6, we divided them into three groups according to the levels of disease activity change from baseline to week 6: worsening or no improvement (≤ 0%, group 1), slight or moderate improvement (0.1–49.9%, group 2), substantial improvement (≥ 50.0%, group 3). Regarding DAS28, patients in groups 2 and 3 had 2.11 and 2.72 times more likely to discontinue GC respectively, compared with patients in group 1 (p for trend = 0.015) in fully adjusted model (Table 4). Similar trends were observed in terms of SDAI and CDAI although not reaching significance.

Table 4 Association of disease activity score changes at week 6 with subsequent GC discontinuationSecondary Analysis: Predictors for Successful GC Discontinuation

In 124 patients who stopped GC, clinical data and follow-up information in 6 months after GC cessation were available in 115 patients, including 91 patients with successful GC discontinuation. In the comparison between successful GC discontinuation and continued groups, multivariate Cox analysis showed increasing age with HR of 0.99 (p = 0.048) and concomitant NSAIDs usage at GC initiation with HR 0.529, p = 0.063).

Similarly, all patients were divided into four groups according to the levels of disease activity from baseline to month 3: worsening or no improvement (≤ 0%, group 1), slight improvement (0.1–24.9%, group 2), moderate improvement (25.0–49.9%, group 3) and substantial improvement (≥ 50.0%, group 4). RegradingDAS28, patients in groups 2, 3, and 4 were 2.81, 4.75, and 5.01 times more likely to successfully discontinue GC, compared with patients in group 1 in fully adjusted model (Table 5). Similar findings were detected for CDAI and SDAI regarding the outcome of successful GC discontinuation.

Table 5 Association of disease activity score changes at 3 months with subsequent successful GC discontinuation

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