Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02196701

Acronym

CLEAR

Enrollment

Registered

2014-07-22

Start date

2014-08-05

Completion date

2017-03-17

Last updated

2018-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Psoriasis

Keywords

methotrexate, adalimumab, biologic, psoriasis, Tumor necrosis factor (TNF)-α inhibitor

Brief summary

The purpose of this study is to determine the safety and efficacy of the use of the combination therapy adalimumab (ADA) every other week (EOW) with methotrexate (MTX) in suboptimal responders to ADA monotherapy.

Interventions

DRUGAdalimumab

Administered by subcutaneous injection every other week.

DRUGMethotrexate

Methotrexate was provided as 2.5 mg tablets for oral administration.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

Inclusion criteria

1. Subjects who have been on ADA monotherapy (40 mg eow or greater) for at least 16 weeks but who in the opinion of the Investigator have shown a sub-optimal response to treatment and have a Physician's Global Assessment (PGA) of ≥ 3 and a Psoriasis Area Severity Index (PASI) of ≥ 5; or Subjects who after an initial positive response to ADA monotherapy (40 mg eow or greater) have failed to maintain an optimal level of response, based on the opinion of the Investigator, and have a PGA of ≥ 3 and a PASI of ≥ 5; 2. Subjects who are receiving 40 mg ADA once weekly must be on ADA 40 mg eow for 8 weeks prior to screening; 3. Subjects with at least a 6 month history of chronic plaque psoriasis; 4. Subjects greater than or equal to 18 years of age; 5. If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile or is of childbearing potential and is practicing birth control; 6. The results of the serum pregnancy test performed during the Screening Period and urine pregnancy test performed at the Baseline Visit must be negative; 7. Subject is judged to be in good general health as determined by the Principal Investigator; 8. Subjects must be evaluated for latent tuberculosis (TB) infection; 9. Subjects must be able and willing to provide written informed consent and comply with the requirements of the study protocol; 10. Subjects must be willing and able to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion criteria

1. Subject has any contraindications to MTX or ADA; 2. Subject has a previous failed response or poor tolerance to ADA; 3. Subject has a poorly controlled medical condition which, in the opinion of the Investigator, would put the subject at risk by participation in the study; 4. Subject has a history of clinically significant hematologic, renal or liver disease; 5. Subject has a history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease; 6. Subject has evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix; 7. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit; 8. Subject is known to have immune deficiency, history of human immunodeficiency virus (HIV) or is immunocompromised; 9. Subject currently uses or plans to use anti-retroviral therapy at any time during the study; 10. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or for 150 days after the last dose of study medication; 11. Subject has a history of clinically significant drug or alcohol usage in the last year or cannot maintain an alcohol intake of 30 g a day or less throughout the study (one standard drink is defined as 180 mL/6 oz (approx. 10 g) of wine, 360 mL/12 oz (approx. 15 g) of regular beer, or 45 mL/1.5 oz (approx. 10 g) of spirits; 12. Screening clinical laboratory analyses show any of the following abnormal laboratory results: * Aspartate transaminase (AST) or alanine transaminase (ALT) \> 2x the upper limit of normal (ULN); * Serum total bilirubin \> 1.5 mg/dL (\> 26 micromol/L), except for subjects with Gilbert's Syndrome; * Creatinine \> 1.5 mg/dL (133 micromol/L) in subjects ≤ 65 years old and \> upper limit of normal range in subjects \> 65; * Positive Hepatitis B or C serology indicative of previous or current infection. 13. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study; 14. The following treatments are prohibited for all subjects during the study: * Phototherapy (ultraviolet A with psoralen \[PUVA\] within 4 weeks of the Baseline Visit and/or ultraviolet B (UVB) within 2 weeks of the Baseline Visit); * Other biologic therapies (including any other anti-tumor necrosis factor \[TNF\]) within 4 weeks of the Baseline Visit; * Any investigational agents of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to the Baseline visit ; * Any other systemic drug therapies for psoriasis within 4 weeks of the Baseline Visit; * Oral or injectable corticosteroids, new prescription topical therapies, or changes in the concentration of current prescription topical therapies (including corticosteroids) that are being used, within 2 weeks of the Baseline Visit. Subjects may continue using previously prescribed topical therapies (including corticosteroids) during the study. 15. Prior exposure to biologics that have a potential or known association with progressive multifocal leukoencephalopathy (PML), i.e., natalizumab (Tysabri®) or rituximab (Rituxan®); 16. Subjects with any active viral infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study;

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment	Week 16	Study investigators were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.
Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment	Week 16	Participants were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.

Secondary

Measure	Time frame	Description
Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline, weeks 8, 16, and 24	Study investigators were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied
Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline, weeks 8, 16, and 24	Participants were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 50 Response Over Time	Baseline and Weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 50 response is defined as at least a 50% reduction (improvement) from baseline in PASI score.
Percentage of Participants Who Achieved a PASI 75 Response Over Time	Baseline and Weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from baseline in PASI score.
Percentage of Participants Who Achieved a PASI 90 Response Over Time	Baseline and Weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is defined as at least a 90% reduction (improvement) from baseline in PASI score.
Percentage of Participants Who Achieved a PASI 100 Response Over Time	Baseline and Weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is defined as a 100% reduction (improvement) from baseline in PASI score.
Change From Baseline in PASI Score Over Time	Baseline and weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).
Percentage of Participants Achieving a Satisfactory Response Based on Investigator Assessment Over Time	Baseline, week 8 and week 24	Study investigators were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.
Percentage of Participants Who Achieved a DLQI Score of 0 or 1 Over Time	Baseline and Weeks 8, 16, and 24	The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all.
Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24	Baseline and week 24	—
Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared or Minimal Over Time	Weeks 8, 16, and 24	The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: * 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; * 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; * 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; * 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; * 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; * 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.
Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Baseline and weeks 8, 16, and 24	The total body surface area affected by psoriasis (expressed as a percentage) was measured by the investigator using the palm method, where the participant's hand represents 1% of body surface area. A decrease in BSA affected by psoriasis indicates improvement.
Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Baseline and weeks 8, 16, and 24	The total body surface area affected by psoriasis (expressed as a percentage) was measured by the investigator using the palm method, where the participant's hand represents 1% of body surface area. A decrease in BSA affected by psoriasis indicates improvement.
Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Baseline, weeks 8, 16, and 24	The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. A negative change from Baseline indicates improvement.
Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Baseline, weeks 8, 16, and 24	The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. A negative change from Baseline indicates improvement.
Percent Change From Baseline in PASI Score	Baseline and weeks 8, 16, and 24	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).
Percentage of Participants Achieving a Satisfactory Response Based on Patient Self-assessment Over Time	Baseline, week 8 and week 24	Participants were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.

Participant flow

Recruitment details

This single-arm, open-label longitudinal study was conducted at 12 sites in Canada from 5 August 2014 to 17 March 2017. The study entailed a screening period up to 35 days, a 24-week treatment period, and a 70-day safety follow-up period. Participants continued to receive adalimumab (ADA) and had oral methotrexate (MTX) added to their treatment.

Pre-assignment details

This study enrolled participants who in the opinion of the Investigator were not responding optimally to adalimumab monotherapy at least 16 weeks after initiating treatment (primary sub-optimal responders) or who after an initial positive response to ADA monotherapy failed to maintain an optimal level of response (secondary sub-optimal responders).

Participants by arm

Arm	Count
Primary Sub-optimal Responders - ADA + MTX Participants who did not respond optimally to ADA monotherapy at least 16 weeks after initiating treatment (primary sub-optimal responders) received 40 mg adalimumab every other week and methotrexate, between 7.5 and 25 mg/week at the discretion of the Investigator, for 24 weeks.	6
Secondary Sub-optimal Responders - ADA + MTX Participants who after an initial positive response to ADA monotherapy failed to maintain an optimal level of response (secondary sub-optimal responders) received 40 mg adalimumab every other week and methotrexate, between 7.5 and 25 mg/week at the discretion of the Investigator, for 24 weeks.	40
Total	46

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Lost to Follow-up	1
Overall Study	Non-adherence to Protocol	1

Baseline characteristics

Characteristic	Primary Sub-optimal Responders - ADA + MTX	Secondary Sub-optimal Responders - ADA + MTX	Total
Age, Continuous	41.0 years STANDARD_DEVIATION 13.84	47.3 years STANDARD_DEVIATION 11.91	46.5 years STANDARD_DEVIATION 12.2
Age, Customized 40 - 64 years	4 Participants	22 Participants	26 Participants
Age, Customized < 40 years	2 Participants	13 Participants	15 Participants
Age, Customized ≥ 65 years	0 Participants	5 Participants	5 Participants
Duration of Psoriasis	20.623 years STANDARD_DEVIATION 10.4819	21.760 years STANDARD_DEVIATION 9.7403	21.612 years STANDARD_DEVIATION 9.7253
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	39 Participants	45 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	2 Participants	8 Participants	10 Participants
Race/Ethnicity, Customized Black	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White	4 Participants	31 Participants	35 Participants
Sex: Female, Male Female	2 Participants	9 Participants	11 Participants
Sex: Female, Male Male	4 Participants	31 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 46
other Total, other adverse events	27 / 46
serious Total, serious adverse events	1 / 46

Outcome results

Primary

Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment

Study investigators were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.

Time frame: Week 16

Population: Participants who received at least one dose of ADA and one dose of MTX. Participants with missing values at week 16 were categorized as non-responders.

Arm	Measure	Value (NUMBER)
Primary Sub-optimal Responders - ADA + MTX	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment	33.3 percentage of participants
Secondary Sub-optimal Responders - ADA + MTX	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment	52.5 percentage of participants
Adalimumab + Methotrexate	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment	50.0 percentage of participants

Primary

Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment

Participants were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses.

Time frame: Week 16

Population: Participants who received at least one dose of ADA and one dose of MTX. Participants with missing values at week 16 were categorized as non-responders.

Arm	Measure	Value (NUMBER)
Primary Sub-optimal Responders - ADA + MTX	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment	16.7 percentage of participants
Secondary Sub-optimal Responders - ADA + MTX	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment	52.5 percentage of participants
Adalimumab + Methotrexate	Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment	47.8 percentage of participants

Secondary

Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis

The total body surface area affected by psoriasis (expressed as a percentage) was measured by the investigator using the palm method, where the participant's hand represents 1% of body surface area. A decrease in BSA affected by psoriasis indicates improvement.

Time frame: Baseline and weeks 8, 16, and 24

Population: Participants who received at least one dose of ADA and one dose of MTX. A mixed-effect model repeat measurement was used.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 16	-4.5 percentage of body surface area	Standard Error 2.4
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 8	-3.5 percentage of body surface area	Standard Error 2.95
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 24	-4.1 percentage of body surface area	Standard Error 1.57
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 16	-6.4 percentage of body surface area	Standard Error 1.08
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 8	-4.5 percentage of body surface area	Standard Error 1.06
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 24	-6.3 percentage of body surface area	Standard Error 0.89
Adalimumab + Methotrexate	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 8	-4.4 percentage of body surface area	Standard Error 0.98
Adalimumab + Methotrexate	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 24	-6.0 percentage of body surface area	Standard Error 0.79
Adalimumab + Methotrexate	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Week 16	-6.2 percentage of body surface area	Standard Error 0.99

Secondary

Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time

The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. A negative change from Baseline indicates improvement.

Time frame: Baseline, weeks 8, 16, and 24

Population: Participants who received at least one dose of ADA and one dose of MTX. A mixed-effect model repeat measurement was used.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 16	-3.8 units on a scale	Standard Error 2.54
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 8	-5.0 units on a scale	Standard Error 1.4
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 24	-1.7 units on a scale	Standard Error 4.29
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 16	-5.9 units on a scale	Standard Error 0.78
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 8	-4.8 units on a scale	Standard Error 0.71
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 24	-6.3 units on a scale	Standard Error 0.69
Adalimumab + Methotrexate	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 8	-4.8 units on a scale	Standard Error 0.64
Adalimumab + Methotrexate	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 24	-5.4 units on a scale	Standard Error 0.88
Adalimumab + Methotrexate	Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time	Week 16	-5.6 units on a scale	Standard Error 0.76

Secondary

Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24

Time frame: Baseline and week 24

Population: Participants who received at least one dose of ADA and one dose of MTX. A mixed-effect model repeat measurement was used.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24	-2.6 mg/L	Standard Error 0.47
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24	0.1 mg/L	Standard Error 1.52
Adalimumab + Methotrexate	Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24	-0.3 mg/L	Standard Error 1.32

Secondary

Change From Baseline in PASI Score Over Time

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

Time frame: Baseline and weeks 8, 16, and 24

Population: Participants who received at least one dose of ADA and one dose of MTX. A mixed-effect model repeat measurement was used.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 24	-3.1 units on a scale	Standard Error 3.17
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 16	-4.5 units on a scale	Standard Error 1.31
Primary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 8	-4.6 units on a scale	Standard Error 2.07
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 16	-6.2 units on a scale	Standard Error 0.59
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 8	-4.6 units on a scale	Standard Error 0.65
Secondary Sub-optimal Responders - ADA + MTX	Change From Baseline in PASI Score Over Time	Week 24	-6.3 units on a scale	Standard Error 0.68
Adalimumab + Methotrexate	Change From Baseline in PASI Score Over Time	Week 8	-4.6 units on a scale	Standard Error 0.61
Adalimumab + Methotrexate	Change From Baseline in PASI Score Over Time	Week 24	-5.9 units on a scale	Standard Error 0.74
Adalimumab + Methotrexate	Change From Baseline in PASI Score Over Time	Week 16	-5.9 units on a scale	Standard Error 0.53

Secondary

Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time

Study investigators were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied

Time frame: Baseline, weeks 8, 16, and 24

Population: Participants who received at least one dose of ADA and one dose of MTX with available data at each time point.

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Completely satisfied	0 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Highly satisfied	0 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Slightly satisfied	8 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Moderately dissatisfied	31 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Completely dissatisfied	1 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Missing	1 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Slightly satisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Missing	2 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Completely satisfied	11 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Highly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Moderately dissatisfied	6 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Completely dissatisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Baseline	Missing	0 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Completely satisfied	6 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Highly satisfied	14 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Slightly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 8	Moderately dissatisfied	9 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Completely satisfied	8 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Highly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Slightly satisfied	10 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Moderately dissatisfied	8 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 16	Completely dissatisfied	3 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Completely dissatisfied	4 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time	Week 24	Missing	3 Participants

Secondary

Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time

Participants were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: * Completely dissatisfied * Moderately dissatisfied * Slightly satisfied * Highly satisfied * Completely satisfied

Time frame: Baseline, weeks 8, 16, and 24

Population: Participants who received at least one dose of ADA and one dose of MTX and with available data at each time point..

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Highly satisfied	2 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Slightly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Completely dissatisfied	2 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Missing	1 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Completely satisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Completely satisfied	10 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Highly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Completely satisfied	5 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Moderately dissatisfied	17 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Completely dissatisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Baseline	Missing	0 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Completely satisfied	10 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Highly satisfied	12 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Slightly satisfied	14 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 8	Moderately dissatisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Highly satisfied	15 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Slightly satisfied	13 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Moderately dissatisfied	6 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Completely dissatisfied	3 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 16	Missing	2 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Slightly satisfied	7 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Moderately dissatisfied	6 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Completely dissatisfied	5 Participants
Primary Sub-optimal Responders - ADA + MTX	Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time	Week 24	Missing	3 Participants

Secondary

Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared or Minimal Over Time

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: * 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; * 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; * 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; * 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; * 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; * 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.

Time frame: Weeks 8, 16, and 24