Phase II Study to Analyze Sarilumab in Non-Infectious Uve... | NCT01900431

NCT01900431

ID	Type	Description	Link
2012-004845-34
U1111-1130-6500	Other Identifier	UTN

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Placebo (for Sarilumab) subcutaneous (SC) injection every 2 weeks (q2w) for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with Methotrexate (MTX) 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).	Drug: Sarilumab Drug: Prednisone Drug: Methotrexate Drug: Folic/folinic acid Other: Placebo (for Sarilumab)
Sarilumab 200 mg q2w	Experimental	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).	Drug: Sarilumab Drug: Prednisone Drug: Methotrexate Drug: Folic/folinic acid

Name	Type	Description	Arm Group Labels	Other Names
Sarilumab	Drug	Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous	Placebo Sarilumab 200 mg q2w

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16	At least 2-step reduction in VH per central review from baseline was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 [low opacity] to 8 [more opacity]) images (in increasing order of opacity) are equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Participants with prednisone dose <10 mg/day (or equivalent oral corticosteroid) were also evaluated.	Week 16

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in VH Scale at Week 16	Change from baseline in VH scale was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 [low opacity] to 8 [more opacity]) images (in increasing order of opacity) were equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Least squares (LS) mean was calculated using mixed model for repeated measurements (MMRM) model with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects as well as fixed continuous covariate of baseline adjudicated VH.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

≥18 years of age.
Non-infectious intermediate, posterior, or pan-uveitis in the study eye.
Active disease at screening or evidence of activity within the 3 months prior to screening visit. Following the approval of amendment-2, only participants with "active disease" as defined above were enrolled in the study.
Starting oral prednisone dose must be greater than or equal to 15 mg/day and less than 80 mg/day.
At screening, participants must be receiving oral prednisone (≥15 mg and <80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with MTX (≤25 mg/week) orally or intravenously or intramuscular or subcutaneous). -
Participants could be receiving one or several of the following therapies: Azathioprine (≤2.5 mg/kg/day), Mycophenolate mofetil (≤2 g daily, orally), Cyclosporine (≤4 mg/kg daily, orally), Tacrolimus (≤4 mg daily, orally).
The doses might not had been increased for at least 4 weeks prior to the randomization visit.
At randomization, participants had been receiving oral prednisone (≥15 mg and <80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with MTX (≤25 mg/week) orally or intravenously or intramuscular or subcutaneous).
Azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus had to be permanently discontinued at least 48 hours prior to the first study treatment injection, or longer as per Investigator's judgment. These immunomodulatory therapies (IMTs) were not permitted anytime during the treatment period.
Signed written informed consent.

Exclusion criteria:

Participants with best-corrected visual acuity (BCVA) worse than 20 early treatment diabetic retinopathy study (ETDRS) letters in at least one eye.
Participants with confirmed or suspected uveitis of infectious etiology or uveitis of traumatic etiology.
Participants with primary diagnosis of anterior uveitis.
Prior treatment with anti-interleukin-6 (IL-6) or interleukin-6 receptor complex (IL-6R) antagonist therapies, including tocilizumab and sarilumab.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts/Locations Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840008		Worcester	Massachusetts	01608	United States
Investigational Site Number 840009

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo (for Sarilumab) subcutaneous (SC) injection every 2 weeks (q2w) for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with Methotrexate (MTX) 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG00020 subjects
FG00138 subjects
FG0020 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).
BG001	Sarilumab 200 mg q2w	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00030.0 OG00146.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was performed using combined estimate for odds ratio obtained by combining the log-transformation of odds ratio from Cochran Mantel-Haenszel (CMH) analyses of the different imputed datasets, using Rubin's formulae, and then by back-transforming the combined estimate. The CMH analyses were adjusted for randomization stratification factor VH level (VH >= 4 versus VH <4).	Cochran-Mantel-Haenszel		0.2354	Threshold for significance at 0.05 level.	Odds Ratio (OR)	2.1			2-Sided	90	0.8	5.6			Sarilumab 200 mg q2w vs Placebo

Secondary

Change From Baseline in VH Scale at Week 16

Change from baseline in VH scale was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 [low opacity] to 8 [more opacity]) images (in increasing order of opacity) were equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Least squares (LS) mean was calculated using mixed model for repeated measurements (MMRM) model with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects as well as fixed continuous covariate of baseline adjudicated VH.

Analysis was performed on mITT population. Number of participants analyzed = participants with VH assessment at baseline and post-baseline visits.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Secondary

Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16

Participants with AC cell score = 0 or with ≥2 step reduction from baseline at Week 16 were evaluated. 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 = no cells; grade +0.5 = 1 - 5 cells; grade +1 = 6 - 25 cells; grade +2= 26 - 50 cells; grade +3 = too many to count.

Analysis was performed on mITT population. Number of participants analyzed = participants with non-missing AC cell score at Week 16.

Posted

Number

Percentage of participants

Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Secondary

Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16

BCVA score is based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters, and then at 1 meter. The range of ETDRS is 0 to 100 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline BCVA.

Analysis was performed on mITT population. Number of participants analyzed = participants with BCVA score assessment at baseline and post-baseline visits.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Secondary

Change From Baseline in Central Retinal Thickness (CRT) At Week 16

CRT was measured by spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.

Analysis was performed on mITT population. Number of participants analyzed = participants with CRT assessment at baseline and post-baseline visits.

Posted

Least Squares Mean

Standard Error

µm (microns)

Baseline to Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Secondary

Percent Change From Baseline in CRT at Week 16

CRT was measured by SD-OCT, a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.

Analysis was performed on mITT population. Number of participants analyzed = participants with CRT assessment at baseline and post-baseline visits.

Posted

Least Squares Mean

Standard Error

percent change

Baseline to Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Secondary

Percentage of Participants With CRT Thickness <300 Microns at Week 16

This endpoint was replaced by the percent change from baseline in CRT at Week 16 as this is more clinically relevant. Zero participant was analyzed.

Posted

Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16

Analysis of this endpoint was not performed as no retinal vessel leakage data was collected at Week 16. Zero participants were analyzed.

Posted

Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16

Participants with prednisone dose ≤5 mg/day (or equivalent oral corticosteroid) at Week 16 were evaluated.

Analysis was performed on mITT population. Number of participants analyzed = participants with non-missing data for prednisone (or equivalent oral corticosteroid) dose at Week 16.

Posted

Number

Percentage of participants

Week 16

ID	Title	Description
OG000	Placebo (Part A)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
OG001	Sarilumab 200 mg q2w (Part A)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.

Units	Counts

Secondary

Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration

Serum functional (unbound) sarilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method with a lower limit of quantification (LLOQ) of 294 ng/mL. Concentrations below LLOQ were set to zero for samples at predose. Post-treatment concentrations below LLOQ were replaced by LLOQ/2. The samples were considered non-eligible for the analysis if the previous dosing time was <11 days or >17 days before the sampling time for every other week regimens.

PK population: all participants who received at least one dose or part of a dose of investigational medicinal product (IMP) with at least one post-dose, non-missing serum concentration value and were analyzed according to treatment actually received. Data of this endpoint was planned to be analyzed for Sarilumab 200 mg q2w arm in Part A and B only.

Posted

Mean

Standard Deviation

ng/mL

Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)

ID	Title	Description
OG000	Sarilumab 200 mg q2w (Part A + Part B)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo (Part A + Part B)	Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B).	2	20	13	20
EG001	Sarilumab 200 mg q2w (Part A+ Part B)	Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B).	5	38	25	38
EG002	Sarilumab 200 mg q2w: Open-Label Treatment (Part C)	Non-responders and non-completers observed in Part A were proposed to be treated with Sarilumab 200 mg SC injection q2w for 34 weeks as open-label treatment in open-label treatment period (Part-C) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.	0	21	15	21

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected38 at risk EG0020 affected21 at risk
Uveitis	Eye disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected38 at risk EG0020 affected21 at risk
Staphylococcal sepsis	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0010 affected38 at risk EG0020 affected21 at risk
Intraocular pressure increased	Investigations	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0010 affected38 at risk EG0020 affected21 at risk
Liver function test increased	Investigations	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected38 at risk EG0020 affected21 at risk
Hypoaesthesia	Nervous system disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0010 affected38 at risk EG0020 affected21 at risk
Abortion induced	Surgical and medical procedures	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Deep vein thrombosis	Vascular disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0010 affected38 at risk EG0020 affected21 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0014 affected38 at risk EG0021 affected21 at risk
Cataract	Eye disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Retinal infiltrates	Eye disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Uveitis	Eye disorders	MedDra 19.0	Systematic Assessment	EG0002 affected20 at risk EG0016 affected38 at risk EG0021 affected21 at risk
Visual impairment	Eye disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0010 affected38 at risk EG0022 affected21 at risk
Aphthous ulcer	Gastrointestinal disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0022 affected21 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected38 at risk EG0023 affected21 at risk
Nausea	Gastrointestinal disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0013 affected38 at risk EG0021 affected21 at risk
Fatigue	General disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0013 affected38 at risk EG0020 affected21 at risk
Injection site bruising	General disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Injection site swelling	General disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Pyrexia	General disorders	MedDra 19.0	Systematic Assessment	EG0002 affected20 at risk EG0010 affected38 at risk EG0020 affected21 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Bronchitis	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0002 affected20 at risk EG0011 affected38 at risk EG0020 affected21 at risk
Ear infection	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Influenza	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0014 affected38 at risk EG0022 affected21 at risk
Nasopharyngitis	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0012 affected38 at risk EG0026 affected21 at risk
Upper respiratory tract infection	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0012 affected38 at risk EG0021 affected21 at risk
Urinary tract infection	Infections and infestations	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0022 affected21 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDra 19.0	Systematic Assessment	EG0004 affected20 at risk EG0013 affected38 at risk EG0021 affected21 at risk
Contusion	Injury, poisoning and procedural complications	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0021 affected21 at risk
Alanine aminotransferase increased	Investigations	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Dizziness	Nervous system disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0013 affected38 at risk EG0020 affected21 at risk
Headache	Nervous system disorders	MedDra 19.0	Systematic Assessment	EG0002 affected20 at risk EG0014 affected38 at risk EG0022 affected21 at risk
Hypoaesthesia	Nervous system disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Middle insomnia	Psychiatric disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 19.0	Systematic Assessment	EG0003 affected20 at risk EG0014 affected38 at risk EG0020 affected21 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDra 19.0	Systematic Assessment	EG0000 affected20 at risk EG0012 affected38 at risk EG0020 affected21 at risk
Behcet's syndrome	Vascular disorders	MedDra 19.0	Systematic Assessment	EG0001 affected20 at risk EG0011 affected38 at risk EG0023 affected21 at risk

ID	Term
D014605	Uveitis

ID	Term
C000592401	sarilumab
D011241	Prednisone
D008727	Methotrexate
D002955	Leucovorin

Ancestor Terms

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D003067	Coenzymes
D045762	Enzymes and Coenzymes

ID	Term
D014603	Uveal Diseases
D005128	Eye Diseases