Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis

Table 1 Predictive factors for cyclosporine response

	Responders (n = 19)	Non-responders(n = 10)	P value
Clinical factor
Fever (°C) ≥ 38.5: < 38.5	10:9	6:4	P = 1.000 NS
Hb (g/dL)	10.6	9.8	P = 0.317 NS
CAI score	14.6	15.0	P = 0.575 NS
Age (yr)	32.8	34.3	P = 0.804 NS
Duration (mo)	67.7	57.9	P = 0.703 NS
CRP (mg/dL)	6.5	3.6	P = 0.104 NS
Endoscopic finding
Endoscopic index	9.9	10	P = 0.819 NS
Deep or geographical ulcer	89.5% (17:2)	50% (5:5)	P = 0.111 NS
Mucosal bleeding	42.1% (8:11)	100% (10:0)	P = 0.004
Poor extensibility	31.6% (6:13)	70% (7:3)	P = 0.064 NS
Pus-like discharge	89.5% (17:2)	90% (9:1)	P = 1.000 NS

UC: Ulcerative colitis; CAI: Clinical activity index; CRP: C-reactive protein.

Table 2 Demographic data and clinical features of responders

	Total (n = 15)
Sex (patient number)
Male	9
Female	6
Age at onset (yr; mean ± SE)	26.2 ± 3.5
Age at CyA treatment (yr; mean ± SE)	30.5 ± 3.8
Duration of UC (months; mean ± SE)	62.3 ± 19.2
Disease extent (patient number)
Pancolitis	12
Left-sided colitis	3
Clinical course (patient number)
Relapse-remitting	11
Chronic continuous	3
Acute fulminating	1
Initial attack	0

Table 3 Clinical data and outcome of responders to CyA therapy

					Endoscopic findings1			Clinical factors1
Case No.	Age	Sex	Duration of UC	Disease extent	Poor extensibility	Deep ulcer	Mucosal bleeding	CAI	CRP	Hgb	Outcome
1	23	F	24M	Pancolitis	(-)	(+)	(-)	17	3.2	9.3	Operation at 4M
2	37	M	67M	Pancolitis	(-)	(+)	(+)	16	1.5	10.9	No operation
3	23	M	44M	Pancolitis	(-)	(+)	(-)	15	7.0	13.7	Operation at 1Y, 4M
4	32	F	77M	Pancolitis	(-)	(-)	(-)	14	1.3	8.6	Operation at 2Y, 10M
5	31	F	26M	Pancolitis	(-)	(-)	(-)	13	12.8	13.4	No operation
6	9	F	13M	Pancolitis	(-)	(-)	(-)	15	12.5	13.2	Operation at 5M
7	16	M	79M	Lt-sided colitis	(-)	(+)	(-)	15	12.8	11.9	Operation at 1M
8	16	F	1M	Pancolitis	(-)	(+)	(-)	17	8.1	8.7	No operation
9	31	M	65M	Lt-sided colitis	(-)	(+)	(-)	12	14.7	10.0	No operation
10	21	M	22M	Pancolitis	(-)	(+)	(-)	17	6.4	11.8	No operation
11	49	M	27M	Lt-sided colitis	(+)	(+)	(+)	13	13.7	7.8	No operation
12	29	F	47M	Pancolitis	(+)	(+)	(+)	13	4.6	8.0	No operation
13	61	M	9M	Pancolitis	(+)	(+)	(-)	15	0.4	10.7	No operation
14	54	M	300M	Pancolitis	(+)	(+)	(+)	12	7.1	13.5	No operation
15	26	M	134M	Pancolitis	(+)	(+)	(+)	18	4.1	10.9	Operation at 2M

¹At beginning of cyclosporine treatment; M: Months; Y: Years. CAI: Clinical activity index; CRP: C-reactive protein; UC: Ulcerative colitis.

Table 4 Following therapies for initial cyclosporine responders

Maintenance therapy	Total(n = 15)	Outcome
		Colectomy (n = 6)	No colectomy (n = 9)
Without azathioprine
PSL	1	1
5-ASA+PSL	4	3	1
PSL+neoral	1	1
5-AZA+PSL+neoral+LCAP	1	1
With azathioprine
5-ASA+PSL+AZA	1		1
5-ASA+PSL+neoral+AZA	5		5
5-ASA+PSL+neoral+TAC+AZA	1		1
5-ASA+PSL+neoral+LCAP+AZA	1		1

PSL: Prednisolone; LCAP: Leukocytapheresis; AZA: Azathioprine; LCAP: Leukocytapheresis; TAC: Tacrolimus.

Table 5 Demographic data and clinical features of patients according to long-term prognosis

	Colectomy (n = 6)	No colectomy (n = 9)	P value
Male:Female (patient no.)	2:4	6:3	P = 0.315 NS
Age at onset (yr; mean ± SE)	17.0 ± 2.8	32.3 ± 4.6	P = 0.063 NS
Age at CyA treatment (yr; mean ± SE)	21.5 ± 3.3	36.6 ± 5.1	P = 0.099 NS
Duration of UC (mo; mean ± SE)	61.8 ± 18.1	62.7 ± 30.6	P = 0.982 NS
CAI score pre-CyA (mean ± SE)	15.7 ± 0.6	14.2 ± 0.7	P = 0.164 NS
CAI score post-CyA (mean ± SE)	5.0 ± 1.0	5.6 ± 1.2	P = 0.732 NS
CRP pre-CyA (mean ± SE)	6.8 ± 2.0	7.7 ± 1.7	P = 0.726 NS
Hb (mean ± SE)	11.3 ± 0.8	10.5 ± 0.7	P = 0.520 NS
Disease extent (patient No.)
Pancolitis: Lt-sided colitis	5:1	7:2	P = 1.000 NS
Clinical course (patient No.)			P = 0.446 NS
Relapse-remitting	4	7
Chronic continuous	1	2
Acute fulminating	1	0
Initial attack	0	0
Endoscopic findings
Poor extensibility (+):(-)	1:5	4:5	P = 0.584 NS
Deep ulcer (+):(-)	4:2	8:1	P = 0.523 NS
Mucosal bleeding (+):(-)	1:5	4:5	P = 0.580 NS

CAI: Clinical activity index; CRP: C-reactive protein; UC: Ulcerative colitis.

Table 6 Outcome according to each following therapy after cyclosporine

	Colectomy (n = 6)	No colectomy (n = 9)	P value
Maintenance therapy
PSL	6	9
LCAP	1	0	P = 0.4000 NS
5-ASA	4	9	P = 0.1429 NS
Neoral	2	7	P = 0.1357 NS
AZA	0	8	P = 0.0014

PSL: Prednisolone; LCAP: Leukocytapheresis; AZA: Azathioprine.