Treatment of experimental adjuvant arthritis with a novel folate receptor-targeted folic acid-aminopterin conjugate

Table 1 EC0746 anti-arthritis activity in comparison with methotrexate and etanercept

Treatment	Dose	Frequency	Inhibition in paw edema (%)^a	Splenomegaly^b	Body weight change (%)^c
Control	-	-	0	117 ± 22	-16 ± 1
EC0746 (s.c.)	25 nmol/kg	Biweekly	0 ± 25^d	73 ± 8^e	-17 ± 1
	100 nmol/kg	Biweekly	35 ± 11^d	52 ± 13^e	-14 ± 1
	250 nmol/kg	Biweekly	91 ± 4^d	25 ± 6^e	-0.5 ± 3
	500 nmol/kg	Biweekly	91 ± 9	37 ± 7	0.4 ± 4
	1,000 nmol/kg	Once weekly	72 ± 12	39 ± 5	-7 ± 3
MTX (p.o.)	250 nmol/kg	Biweekly	70 ± 5	42 ± 17	-14 ± 2
	1,650 nmol/kg	Once weekly	47 ± 10^f	-	-10 ± 2
MTX (s.c.)	250 nmol/kg	Biweekly	78 ± 10	24 ± 3	-2 ± 4
	1,650 nmol/kg	Once weekly	63 ± 13^f	-	-7 ± 8
Etanercept (s.c.)	10 mg/kg	Every 3 days	46 ± 9^f	42 ± 7	-15 ± 2

Rats with adjuvant arthritis were treated at disease onset (10 days post arthritis induction) with EC0746, methotrexate (MTX), and etanercept at indicated doses, dosing routes, and dosing frequencies. s.c., subcutaneously; p.o., per orally. ^aInhibition in paw edema is calculated based on paw weight on day 24: 100 × (arthritic control - treated)/(arthritic control - healthy). ^bSplenomegaly is defined as the percentage increase in spleen weight relative to the spleen weights of healthy rats. ^cOn day 24 relative to body weight on the first day of treatment (day 10). Linear regression analysis: ^dR² = 1.00 (paw) and ^eR² = 0.99 (spleen). ^fCalculated based on arthritis scores on day 24 (paw weights were not obtained).

ISSN: 1478-6362