For adult patients with non-infectious (NI) intermediate, posterior, or panuveitis

Disease control in adult patients with NI uveitis^1,*

*Non-infectious (NI) intermediate, posterior, or panuveitis.

VISUAL I &
VISUAL II

Adult patients with non-infectious (NI) intermediate, posterior, or panuveitis^1-3

VISUAL I study design intro: Double-masked trial of adult patients with active^† non-infectious intermediate, posterior, or panuveitis. 217 patients were randomized to receive placebo (n=107) or HUMIRA 80 mg loading dose (Week 0) followed by HUMIRA 40 mg EOW starting at Week 1 after the initial dose (n=110). The primary endpoint was time to treatment failure assessed first at Week 6 and every visit thereafter.^1,2,‡

VISUAL II study design intro: Double-masked trial of adult patients with inactive^§non-infectious intermediate, posterior, or panuveitis. 226 patients were randomized to receive placebo (n=111) or HUMIRA 80 mg loading dose (Week 0) followed by HUMIRA 40 mg EOW starting at Week 1 after the initial dose (n=115). The primary endpoint was time to treatment failure assessed first at Week 2 and every visit thereafter.^1,3,‡

^†Active disease was defined as ≥1 of the following parameters in at least 1 eye despite ≥2 weeks of oral glucocorticoid use: active inflammatory chorioretinal or retinal vascular lesion, ≥2+ anterior chamber (AC) cell grade, ≥2+ vitreous haze (VH) grade.²
^‡Treatment failure was defined as the presence of any 1 of the 4 markers of disease activity in at least 1 eye.^1-3
^§Inactive disease was defined as eyes with no inflammatory chorioretinal or vascular retinal lesions, anterior chamber (AC) cell grade of ≤0.5+, vitreous haze (VH) cell grade ≤0.5+.³

EOW=Every other week

Time to treatment failure on or after Week 6^1,2,*^,†

HUMIRA (n=110)
Placebo (n=107)

*Mandatory steroid taper from Week 2 to Week 15.²

^†Treatment failure at or after Week 6 was counted as an event. Subjects who discontinued the study were censored at the time of dropping out.¹

Differences in disease control between HUMIRA and placebo were seen as early as Week 6, the first time point measured¹
At Month 3, the treatment failure rate for HUMIRA was nearly half the rate for placebo: 25% for HUMIRA (n=25) vs 48% for placebo (n=49)⁴
By Month 6, the treatment failure rate was 50% for HUMIRA (n=48) vs 78% for placebo (n=76)⁴

CI=confidence interval; EOW=every other week

Time to treatment failure on or after Week 2^1,3,*^,†

HUMIRA (n=115)
Placebo (n=111)

Hazard ratio=0.57

(95% CI, 0.39-0.84, P=0.004)

*Mandatory steroid taper from Week 2 to Week 19.³

^†Treatment failure at or after Week 2 was counted as an event. Subjects who discontinued the study were censored at the time of dropping out.¹

Differences in disease control between HUMIRA and placebo were seen as early as Week 2, the first time point measured¹
Median time to treatment failure: Not estimable for HUMIRA vs 8.3 months for placebo (95% CI, 4.8–12.0)^1,3
HUMIRA patients had a 43% reduced risk of treatment failure vs placebo (hazard ratio=0.57 [95% CI, 0.39–0.84])^1,3

CI=confidence interval; EOW=every other week

Safety data

The most common adverse reactions in HUMIRA clinical trials (>10%) were infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash¹
There is a known association between intermediate uveitis and central demyelinating disorders¹

	VISUAL I²		VISUAL II³
Adverse Events	HUMIRA (n=111) PYs=62.4	Placebo (n=112) PYs=44.3	HUMIRA (n=115) PYs=94.5	Placebo (n=114) PYs=71.0
Serious adverse events (SAEs)	18 (28.8)	6 (13.6)	13 (13.8)	10 (14.1)
AE leading to discontinuation	13 (20.8)	5 (11.3)	11 (11.6)	7 (9.9)
Serious infections	5 (8.0)	3 (6.8)	3 (3.2)	2 (2.8)
Malignancy	2 (3.2)^a	0	1 (1.1)^b	0
AE leading to death	1 (1.6)^c	0	2 (2.1)^d	0
Any active TB	1 (1.6)	0	0	0
Any latent TB	1 (1.6)	0	3 (3.2)	1 (1.4)
Injection site reactions	28 (44.9)	7 (15.8)	36 (38.1)	16 (22.6)
Any demyelinating disease	1 (1.6)	0	0	0

The safety profile for patients with NI uveitis* treated with HUMIRA was similar to the safety profile seen in patients with RA.¹

^*Non-infectious (NI) intermediate, posterior, or panuveitis.

^aOne event each of carcinoid tumor of the gastrointestinal tract (Day 244; resolved on Day 251; HUMIRA treatment was not interrupted) and glioblastoma multiforme (Day 242; HUMIRA was discontinued due to this event; last HUMIRA dose, Day 248).²
^bOne event of non-serious squamous cell carcinoma of skin (Day 210; resolved on Day 215; HUMIRA treatment was not interrupted).³
^cOne death due to end-stage chronic renal disease (37 days after baseline).²
^dOne death due to 2 fatal AEs of aortic dissection and cardiac tamponade (18 days after last HUMIRA dose).³

PYs=patient-years; TB=tuberculosis

Parameter	HUMIRA (n=115)	Placebo (n=111)
Sex, female; n (%)	66 (57)	72 (65)
Race, white; n (%)	96 (83)	93 (84)
Age, years; mean ± SD	42.9 ± 12.9	42.2 ± 14.0
Type of uveitis, n (%)
Intermediate	17 (15)	30 (27)
Posterior	39 (34)	34 (31)
Panuveitis	57 (50)	46 (41)
Diagnosis, n (%)
Idiopathic uveitis	29 (25)	40 (36)
Birdshot choroidopathy	15 (13)	15 (14)
Multifold choroiditis and panuveitis	5 (4)	2 (2)
Vogt–Koyanagi–Harada disease	26 (23)	25 (23)
Sarcoidosis	18 (16)	14 (13)
Behçet’s disease	10 (9)	6 (5)
Other	12 (10)	9 (8)
Duration of uveitis, months; mean ± SD	59.5 ± 64.5	62.9 ± 67.7
Eye affected, n (%)
Left only	2 (2)	3 (3)
Right only	1 (1)	4 (4)
Both	112 (97)	104 (94)
Number of flares in past 12 months, n (%)
0-1	48 (42)	46 (41)
2	43 (37)	40 (36)
≥3	24 (21)	25 (23)
Concomitant immunomodulators, n (%)
Mycophenolate mofetil	17 (15)	17 (15)
Cyclosporine	15 (13)	11 (10)
Methotrexate	19 (17)	14 (13)
Azathioprine	3 (3)	11 (10)

≥1 criteria for treatment failure met in at least 1 eye	Treatment failure
≥1 criteria for treatment failure met in at least 1 eye	At Week 6	After Week 6
inflammatory chorioretinal and/or retinal vascular lesions	New active inflammatory lesions relative to baseline	New active inflammatory lesions relative to baseline
AC cell grade (SUN criteria)	Inability to achieve ≤0.5+	2-step increase relative to best state achieved
VH grade (NEI/SUN criteria)	Inability to achieve ≤0.5+	2-step increase relative to best state achieved
Visual acuity (ETDRS)	Worsening of BCVA ≥15 letters relative to best state achieved	Worsening of BCVA ≥15 letters relative to best state achieved

≥1 criteria for treatment failure met in at least 1 eye	Treatment failure Assessed at Week 2 and every visit thereafter
≥1 criteria for treatment failure met in at least 1 eye	Inflammatory chorioretinal and/or retinal vascular lesions	New active inflammatory lesions relative to baseline
AC cell grade (SUN criteria)	2-step increase relative to baseline
VH grade (NEI/SUN criteria)	2-step increase relative to baseline
Visual acuity (ETDRS)	Worsening of best corrected visual acuity (BCVA) ≥15 letters

Parameter	HUMIRA (n=110)	Placebo (n=107)
Sex, female; n (%)	59 (54)	65 (61)
Race, white; n (%)	88 (80)	86 (80)
Age, years; mean ± SD	42.7 ± 15.6	42.6 ± 14.2
Type of uveitis, n (%)
Intermediate	24 (22)	23 (21)
Posterior	36 (33)	37 (35)
Panuveitis	50 (45)	47 (44)
Diagnosis, n (%)
Idiopathic uveitis	36 (33)	45 (42)
Birdshot choroidopathy	24 (22)	20 (19)
Multifold choroiditis and panuveitis	8 (7)	3 (3)
Vogt–Koyanagi–Harada disease	11 (10)	14 (13)
Sarcoidosis	10 (9)	8 (7)
Behçet’s disease	12 (11)	4 (4)
Other	9 (8)	13 (12)
Duration of uveitis, months; mean ± SD	40.2 ± 51.2	51.0 ± 72.2
Eye affected, n (%)
Left only	5 (5)	5 (5)
Right only	7 (6)	3 (3)
Both	98 (89)	99 (93)
Number of flares in past 12 months, n (%)
1	18 (16)	19 (18)
2	54 (49)	46 (43)
≥3	38 (35)	42 (39)
Concomitant immunomodulators, n (%)
Mycophenolate mofetil or equivalent	11 (10)	14 (13)
Cyclosporine	10 (9)	3 (3)
Methotrexate	9 (8)	12 (11)
Azathioprine	4 (4)	4 (4)

Disease control in adult patients with NI uveitis^1,*

VISUAL I &
VISUAL II

Time to treatment failure on or after Week 6^1,2,*^,†

VISUAL I: Adults with active disease

Time to treatment failure on or after Week 2^1,3,*^,†

VISUAL II: Adults with inactive disease

Safety data

Summary of adverse events (AEs) during the randomized trial period (events per 100 patient-years)^2,3

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATIONS¹

Corticosteroid eye drop taper³

Corticosteroid eye drop taper²

VISUAL II: A study in adult patients with active non-infectious (NI) intermediate, posterior, or panuveitis^1,3

Model of disease activity: Inactive disease controlled by steroid^1,3,a

Baseline characteristics

Select baseline patient characteristics (ITT population)³

Treatment failure was defined as the presence of any 1 of the 4 markers of disease activity in at least 1 eye.^1,2

Treatment failure was defined as the presence of any 1 of the 4 markers of disease activity in at least 1 eye.^1,3

VISUAL I: A study in adult patients with active non-infectious (NI) intermediate, posterior, or panuveitis^1,2

Model of disease activity: Active disease activity, followed by steroid^1,2,a,b

Baseline characteristics

Select baseline patient characteristics (ITT population)²

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATIONS¹

Dose (mg/day)	Prednisone dose at study entry
Dose (mg/day)	35 mg	30 mg	25 mg	20 mg	15 mg	12.5 mg	10 mg
35	Week 0-1
30	2	Week 0-1
25	3	2	Week 0-1
20	4	3	2	Week 0-1
15	5	4	3	2	Week 0-1
12.5	6	5	4	3	2	Week 0-1
10	7	6	5	4	3	2	Week 0-1
7.5	8	7	6	5	4	3	2
5	9	8	7	6	5	4	3
4	11	10	9	8	7	6	5
3	13	12	11	10	9	8	7
2	15	14	13	12	11	10	9
1	17	16	15	14	13	12	11
Discontinue	19	18	17	16	15	14	13

Week	Prednisone dose (mg/day)
0	60
1	60
2	50
3	40
4	30
5	20
6	15
7	12.5
8	10
9	7.5
10	5
11	4
12	3
13	2
14	1
15	Discontinue prednisone

Dose (# of drops/day) per week
12
10
8
6
5
4
3
2
1
Discontinue drops

Dose (# of drops/day) per week
12
10
8
6
5
4
3
2
1
Discontinue drops

Disease control in adult patients with NI uveitis1,*

VISUAL I & VISUAL II

Time to treatment failure on or after Week 61,2,*,†

VISUAL I: Adults with active disease

Time to treatment failure on or after Week 21,3,*,†

VISUAL II: Adults with inactive disease

Safety data

Summary of adverse events (AEs) during the randomized trial period (events per 100 patient-years)2,3

INDICATION1

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

INDICATIONS1

Model of disease activity: Inactive disease controlled by steroid1,3,a

Select baseline patient characteristics (ITT population)3

Model of disease activity: Active disease activity, followed by steroid1,2,a,b

Select baseline patient characteristics (ITT population)2

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

INDICATION1

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

INDICATION1

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

INDICATION1

INDICATION1

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

INDICATIONS1

Disease control in adult patients with NI uveitis^1,*

VISUAL I &
VISUAL II

Time to treatment failure on or after Week 6^1,2,*^,†

Time to treatment failure on or after Week 2^1,3,*^,†

Summary of adverse events (AEs) during the randomized trial period (events per 100 patient-years)^2,3

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATIONS¹

Model of disease activity: Inactive disease controlled by steroid^1,3,a

Select baseline patient characteristics (ITT population)³

Model of disease activity: Active disease activity, followed by steroid^1,2,a,b

Select baseline patient characteristics (ITT population)²

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATION¹

INDICATION¹

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)¹

INDICATIONS¹