Table 2. studies assessing optimal sequence and timing of csDMARDs and bDMARDs.

Author	Year Published	Data Source	Patient Population	Sample Size	Major Findings
Minden et al. (27)	2019	German BIKER Registry	JIA	701	Early bDMARD treatment is associated with better disease control & outcomes. Patients categorized in 3 groups based on time from symptoms onset to bDMARD start (G1: ≤ 2 yrs, G2: > 2 to ≤ 5 yrs, and G3: > 5 yrs). At 10-yr mark, G1 pts (18.5%) more likely in drug-free remission than G2 (10.1%) & G3 (4.9%). G1 pts also had lower disease activity than G3 pts (cJADAS10 = 4.9 vs. 7.1), better overall well-being (18.2% vs. 8.4%), and higher functional status (59.2% vs. 43.7%). G1 pts also required arthroplasty less frequently than G3 pts and had lower disease activity over time than both G2 & G3 pts.
Huang et al. (25)	2020	EMRs of Cincinnati Children Hospital	Polyarticular JIA	2,082	Compared with csDMARD alone, early aggressive use of bDMARD in treating pts with polyJIA soon after diagnosis achieves > 2 points of additional reduction in disease activity at 6 months. Adding bDMARD after 6 months provides little added benefit.
Kimura et al. (24)	2021	CARRA Patient Registry	Polyarticular JIA	401	No sig differences among groups in achieving the ACR provisional criteria for clinical inactive disease without glucocorticoids in 1 yr. However, a significantly greater likelihood of early combination therapy achieving inactive disease according to cJADAS-10 & ACR Pedi 70.
Yue et al. (26)	2021	EMRs of Cincinnati Children Hospital	Polyarticular JIA	821	The timing of bDMARD initiation was influenced by factors such as # of joints with limited range of motion, erythrocyte sedimentation rate, and JIA category. % of pts using bDMARDs within 3 months of diagnosis each yr exhibited a positive correlation with the proportion of pts achieving inactive/low disease outcomes each yr for polyarthritis pts.
Montag et al. (28)	2022	JuMBO Registry	JIA	1,306	JIA patients with a late start of bDMARDs were significantly more likely to use DMARDs and other medications in adulthood than those with early bDMARD treatment. Early effective treatment in JIA can reduce the need for multiple meds in adulthood.
Ramos et al. (29)	2023	Rheumatic Diseases Portuguese Register (Reuma.pt)	JIA	361	The patients were categorized into three groups based on the time between disease onset and bDMARD initiation: ≤ 2 years, 2-5 years, and > 5 years. Patients who began bDMARD treatment >5 yrs after disease onset were less likely to achieve drug-free remission (OR = 0.24; 95% CI: 0.06 - 0.92; p = 0.038). These patients also had a greater physical disability, worse HRQoL, and required more joint surgeries compared to those who started treatment earlier.