A Study of the Long-term Safety and Efficacy of Adalimumab in Subjects With Intermediate-, Posterior-, or Pan-uveitis

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset date on or after the first dose of study drug and up to 70 days after the last dose. See the Adverse Event section for details.

PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations used include g=grams; L=liters.

PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations include ALT/SGPT=alanine aminotransferase/serum glutamate pyruvate transaminase; AST/SGOT=aspartate aminotransferase/serum glutamate oxaloacetate transaminase; g/L=grams/liter; mmol/L=millimoles/liter; ULN=upper limit of normal.

Heart rate (beats per minute) was measured while the participant was sitting.

Respiratory rate (respirations per minute) was measured while the participant was sitting.

Temperature was measured while the participant was sitting.

Blood pressure was measured while the participant was sitting. Abbreviations used include mmHg=millimeters of mercury.

Quiescence is defined as no active inflammatory lesions and anterior chamber (AC) cell grade ≤ 0.5+ and vitreous haze (VH) grade ≤0.5+. Participants with active uveitis at study entry could have been in quiescence at Week 0 because all participants were evaluated for uveitis status at the Final/Early Termination visit of the lead-in study and the Week 0 visit could have occurred up to 28 days later during which time the participant's disease status may have changed.

Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade > 0.5+ and/or VH grade >0.5+).

Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade > 0.5+ and/or VH grade >0.5+).

Dilated indirect ophthalmoscopy is performed to determine both vitreous haze grading and the absence/presence of inflammatory chorioretinal and/or inflammatory retinal vascular lesions. The number of AC cells observed within a 1 mm * 1 mm slit beam was recorded for each eye and this number was used to determine the grade according to Standardization of Uveitis Nomenclature (SUN) criteria. Grading of VH was based on the National Eye Institute (NEI) publication which was adapted by the SUN working group. The percentage of participants with new active inflammatory lesions or grade ≥2 in AC cells or grade ≥2 in VH are presented.

Steroid-free quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+ and no uveitis-related corticosteroids on the day of assessment.

Percentage of participants, without quiescence, with/without change in concomitant medications within 5 days after non-quiescence and with/without quiescence at next visit at least 8 weeks after non-quiescence among participants with inactive uveitis at study start. Quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+. Abbreviations used are as follows: CM=concomitant medications; NQ=non-quiescence.

Percentage of participants, without quiescence, with/without change in concomitant medications within 5 days after non-quiescence and with/without quiescence at next visit at least 8 weeks after non-quiescence, among participants with active uveitis at study start. Quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+. Abbreviations used include: CM=concomitant medications, NQ=non-quiescence.

Percentage of participants who started uveitis-related systemic corticosteroids during the study.

Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.

Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.

Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants. Data not presented after Week 198 as no participants remained on study as of Week 198.

Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.

Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants. Data presented for participants not using systemic corticosteroids at each timepoint.

Percentage of participants at each study time point without a worsening of Best Corrected Visual Acuity (BCVA) by ≥15 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) in both eyes relative to Baseline for participants who had inactive uveitis when they entered the study.

Percentage of participants at each study time point without a worsening of BCVA by ≥15 letters on the ETDRS in both eyes relative to Week 8 for participant who had active uveitis when they entered the study.

Using corrective lenses based on that visit's refraction testing, participant's BCVA was measured using an ETDRS logMAR chart. On the logMAR scale, 0 is equivalent to 20/20 visual acuity, the range of normal vision is considered to be from -0.2 to 0.1; higher values indicate visual impairment. Data presented includes the mean of both eyes for all participants (active or inactive uveitis) for all study time points.

Central retinal thickness was measured using optical coherence tomography (OCT) and assessed by a central reader. Percent change in left eye from baseline (Week 0) to each study time point relative to baseline for participants who had inactive uveitis at study entry is presented.

Central retinal thickness was measured using optical coherence tomography (OCT) and assessed by a central reader. Percent change in right eye from baseline (Week 0) to each study time point relative to baseline for participants who had inactive uveitis at study entry is presented.

Central retinal thickness was measured using OCT and assessed by a central reader. Percent change in left eye at each study time point relative to Week 8 (baseline) for participants who had active uveitis at study entry is presented.

Central retinal thickness was measured using OCT and assessed by a central reader. Percent change in right eye at each study time point relative to Week 8 (baseline) for participants who had active uveitis at study entry is presented.

Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm * 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0: ˂ 1 cell; Grade 0.5+: 1 - 5 cells; Grade 1+: 6 - 15 cells; Grade 2+: 16 - 25 cells; Grade 3+: 26 - 50 cells; and Grade 4+: ≥ 50 cells.

Immunosuppression load was assessed using a weighted semiquantitative scale, applying grades ranging from 0 to 9 for each immunosuppressive agent on a scale for the total daily dose in milligrams per kilogram per day or per week if dosed weekly. A higher score indicating a higher immunosuppression load and a lower or decreased score indicated improvement or less need for immunosuppressive therapy. The grading scheme was used to accommodate the simultaneous use of multiple agents and provided a combined, single numeric score for the total immunosuppression load per unit body weight per day at each visit. For participants receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit. Data not presented after Week 234 as no participants remained on study as of Week 234.

Immunosuppression load was assessed using a weighted semiquantitative scale, applying grades ranging from 0 to 9 for each immunosuppressive agent on a scale for the total daily dose in milligrams per kilogram per day or per week if dosed weekly. A higher score indicating a higher immunosuppression load and a lower or decreased score indicated improvement or less need for immunosuppressive therapy. The grading scheme was used to accommodate the simultaneous use of multiple agents and provided a combined, single numeric score for the total immunosuppression load per unit body weight per day at each visit. For participants receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit.

Percentage of participants at each study time point with no new active, inflammatory chorioretinal or inflammatory retinal vascular lesion in both eyes relative to Baseline for participants who had inactive uveitis when they entered the study.

Percentage of participants at each study time point with no new active, inflammatory chorioretinal or inflammatory retinal vascular lesion in both eyes relative to Week 8 for participants who had active uveitis when they entered the study.

Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to NEI and SUN criteria:

Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.

The National Eye Institute (NEI) Visual Functioning Questionnaire (VFQ-25) is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning.The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning. Baseline was defined as Week 0 for participants with inactive uveitis.

The National Eye Institute (NEI) Visual Functioning Questionnaire (VFQ-25) is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning.The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning. Baseline was defined as Week 8 for participants with active uveitis.