Background/Purpose:  Enthesitis-related arthritis (ERA) is a JIA category primarily affecting entheses and peripheral joints but can involve the axial skeleton. Disease activity and structural change can adversely affect long-term physical function and quality of life of ERA patients (pts). Adalimumab (ADA) has been previously demonstrated to be effective in children with polyarticular JIA and ERA. Objective of this study is to evaluate the persistence of efficacy and long-term safety of ADA compared to placebo (PBO) in children and adolescents with ERA.

Methods:  This is a phase 3, multicenter, randomized, double-blind (DB) study in ERA pts aged ≥6-<18 years (yr) at baseline (BL). Methods have been previously described. Pts were randomized 2:1 to receive blinded ADA (24 mg/m²BSA up to 40 mg every other week (wk) [eow]) or PBO for 12 wks followed by open-label (OL) ADA eow for up to an additional 192 wks. Primary endpoint was % change from BL in number of active joints with arthritis (AJC) at wk 12. Secondary variables assessed included enthesitis count (EC), tender (TJC) and swollen joint (SJC) counts, and American College of Rheumatology (ACR) Pediatric (Pedi) 30/50/70 responses. Kaplan Meier analysis was used to determine time to achieve SJC=0, TJC=0, and EC=0 from time of first ADA injection. Results are summarized through 156 wks of treatment for efficacy and 204 wks for safety. Safety was assessed in terms of adverse events (AE).

Results: 46 pts were randomized (ADA, n=31; PBO, n=15). No pts discontinued during DB period; 7 pts early escaped to OL ADA. 17 pts discontinued from OL period prior to wk 204 including 4 pts achieving remission. Percentage change from BL at wk 12 in AJC was greater in ADA group vs. PBO (-62.6±59.5 vs -11.6±100.5, P=0.039) with response maintained with continued ADA therapy through 156 wks (-88.3±27.7). During treatment with ADA 95.7%, 89.1%, and 89.1% of pts achieved SJC=0, TJC=0 and, EC=0, respectively. Median time from first dose of ADA to achieving SJC=0, TJC=0, and EC=0 was 41, 108, and 56 days, respectively. At wk 12 ACR Pedi70 was statistically significant in favor of ADA while EC, TJC, SJC, and ACR Pedi30/50 showed numerically greater, but not statistically significant improvement in favor of ADA with responses maintained through wk 156. During DB period AE incidence rates were similar [ADA/PBO (%)]: any AE (67.7/53.3), serious AE (3.2/0), and infectious AEs (29.0/20.0). Among pts who received at least 1 dose of ADA, any AE, serious AEs, infectious AEs, and serious infections were reported in 100%, 21.7%, 89.1%, and 8.7% respectively. Ten pts reported a total of 19 serious AEs through 204 wks of treatment. No deaths or malignancies were reported.

Conclusion:  ADA reduced the signs and symptoms of ERA at wk 12 and efficacy was sustained through 156 wks. Safety profile observed through 204 wks of treatment in pediatric pts with ERA was consistent with that observed in children aged ≥2 yrs treated for polyarticular JIA.

Weeks	% Change from BL in AJCa, mean		Change from BL in ECa, mean		Change from BL in SJCa, mean		ACR Pedi 70 Responderb, n (%)
	PBO N=15	ADA N=31	PBO N=15	ADA N=31	PBO N=15	ADA N=31	PBO N=15	ADA N=31
12	-11.6	-62.6	-2.7	-4.4	-2.4	-3.5	3 (20.0)	17 (54.8)
	Any ADA (N=46)		Any ADA (N=46)		Any ADA (N=46)		Any ADA (N=46)
24	-85.2		-6.8		-5.2		34 (73.9)
52	-88.7		-6.6		-5.7		35 (76.1)
108	-90.5		-6.3		-5.7		36 (78.3)
156	-88.3		-6.0		-5.5		35 (76.1)

^aLOCF. ^bNRI.