Trial Outcomes & Findings for A Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis (NCT NCT03331835)

Last Updated: 2025-03-13

Results Overview

The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

210 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2025-03-13

Participant Flow

Participant milestones

Participant milestones
Measure	Brodalumab Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).	Fumaric Acid Esters Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.
Overall Study STARTED	105	105
Overall Study COMPLETED	91	58
Overall Study NOT COMPLETED	14	47

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Not all participants weighed below 100 kg. This section shows the mean weight of participants weighing less than 100 kg.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).	Total n=210 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Age, Categorical Between 18 and 65 years	96 Participants n=105 Participants	97 Participants n=105 Participants	193 Participants n=210 Participants
Age, Categorical >=65 years	9 Participants n=105 Participants	8 Participants n=105 Participants	17 Participants n=210 Participants
Sex: Female, Male Female	32 Participants n=105 Participants	33 Participants n=105 Participants	65 Participants n=210 Participants
Sex: Female, Male Male	73 Participants n=105 Participants	72 Participants n=105 Participants	145 Participants n=210 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=105 Participants	103 Participants n=105 Participants	203 Participants n=210 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=105 Participants	2 Participants n=105 Participants	7 Participants n=210 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Race (NIH/OMB) Asian	1 Participants n=105 Participants	0 Participants n=105 Participants	1 Participants n=210 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Race (NIH/OMB) Black or African American	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Race (NIH/OMB) White	104 Participants n=105 Participants	105 Participants n=105 Participants	209 Participants n=210 Participants
Race (NIH/OMB) More than one race	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=105 Participants	0 Participants n=105 Participants	0 Participants n=210 Participants
Region of Enrollment Germany	105 participants n=105 Participants	105 participants n=105 Participants	210 participants n=210 Participants
Height	175 cm STANDARD_DEVIATION 9.6 • n=105 Participants	176 cm STANDARD_DEVIATION 9.8 • n=105 Participants	175 cm STANDARD_DEVIATION 9.7 • n=210 Participants
Weight	87.8 kg STANDARD_DEVIATION 20.4 • n=105 Participants	86.6 kg STANDARD_DEVIATION 21.1 • n=105 Participants	87.2 kg STANDARD_DEVIATION 20.7 • n=210 Participants
Mean weight in participants weighing <100 kg	78.4 kg STANDARD_DEVIATION 11.9 • n=79 Participants • Not all participants weighed below 100 kg. This section shows the mean weight of participants weighing less than 100 kg.	77.2 kg STANDARD_DEVIATION 12.8 • n=79 Participants • Not all participants weighed below 100 kg. This section shows the mean weight of participants weighing less than 100 kg.	77.8 kg STANDARD_DEVIATION 12.4 • n=158 Participants • Not all participants weighed below 100 kg. This section shows the mean weight of participants weighing less than 100 kg.
Mean weight in participants weighing >=100 kg	116 kg STANDARD_DEVIATION 13.2 • n=26 Participants • Not all participants weighed over 100 kg. This section shows the mean weight of participants equal to or more than 100 kg	115 kg STANDARD_DEVIATION 13.9 • n=26 Participants • Not all participants weighed over 100 kg. This section shows the mean weight of participants equal to or more than 100 kg	116 kg STANDARD_DEVIATION 13.4 • n=52 Participants • Not all participants weighed over 100 kg. This section shows the mean weight of participants equal to or more than 100 kg
Body mass index (BMI)	28.5 kg/m^2 STANDARD_DEVIATION 5.7 • n=105 Participants	28.0 kg/m^2 STANDARD_DEVIATION 6.0 • n=105 Participants	28.2 kg/m^2 STANDARD_DEVIATION 5.9 • n=210 Participants
Duration of psoriasis	14.3 years STANDARD_DEVIATION 11.5 • n=105 Participants	13.2 years STANDARD_DEVIATION 11.7 • n=105 Participants	13.7 years STANDARD_DEVIATION 11.6 • n=210 Participants
PASI score	17.2 score on a scale STANDARD_DEVIATION 5.9 • n=105 Participants	17.8 score on a scale STANDARD_DEVIATION 6.7 • n=105 Participants	17.5 score on a scale STANDARD_DEVIATION 6.3 • n=210 Participants
sPGA score	3.5 score on a scale STANDARD_DEVIATION 0.6 • n=105 Participants	3.5 score on a scale STANDARD_DEVIATION 0.7 • n=105 Participants	3.5 score on a scale STANDARD_DEVIATION 0.6 • n=210 Participants
BSA score	24.8 score on a scale STANDARD_DEVIATION 15.2 • n=105 Participants	25.5 score on a scale STANDARD_DEVIATION 14.9 • n=105 Participants	25.2 score on a scale STANDARD_DEVIATION 15.1 • n=210 Participants
NAPSI score	6.4 score on a scale STANDARD_DEVIATION 4.4 • n=43 Participants • Not all participants had nail involvement at baseline. Only participants with nail involvement at baseline were included here.	7.7 score on a scale STANDARD_DEVIATION 4.9 • n=38 Participants • Not all participants had nail involvement at baseline. Only participants with nail involvement at baseline were included here.	7.0 score on a scale STANDARD_DEVIATION 4.7 • n=81 Participants • Not all participants had nail involvement at baseline. Only participants with nail involvement at baseline were included here.
DLQI score	18.8 score on a scale STANDARD_DEVIATION 5.2 • n=105 Participants	18.5 score on a scale STANDARD_DEVIATION 4.9 • n=105 Participants	18.7 score on a scale STANDARD_DEVIATION 5.1 • n=210 Participants
PSI score	14.8 score on a scale STANDARD_DEVIATION 5.4 • n=83 Participants • Not all subjects had a baseline PSI measurement.	17.9 score on a scale STANDARD_DEVIATION 5.3 • n=78 Participants • Not all subjects had a baseline PSI measurement.	16.3 score on a scale STANDARD_DEVIATION 5.6 • n=161 Participants • Not all subjects had a baseline PSI measurement.

PRIMARY outcome

Timeframe: Baseline to Week 24

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24	85 Participants	40 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease).

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24	68 Participants	21 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24	69 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24	42 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.

Outcome measures

Outcome measures
Measure	Brodalumab n=100 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=96 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Change From Baseline at Week 24 in PASI Score	-15.69 score on a scale Standard Error 0.59	-12.62 score on a scale Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline to Week 24

Outcome measures

Outcome measures
Measure	Brodalumab n=100 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=96 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Percent Change From Baseline in PASI Score at Week 24	-90.03 percent change in PASI Standard Error 2.25	-73.67 percent change in PASI Standard Error 2.63

SECONDARY outcome

Timeframe: Baseline to Week 24

The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection.

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Change From Baseline at Week 24 in Affected Body Surface Area (BSA)	-20.82 percent change Standard Error 1.48	-11.91 percent change Standard Error 1.48

SECONDARY outcome

Timeframe: Week 24

Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.

The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day.

Outcome measures

Outcome measures
Measure	Brodalumab n=23 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=15 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1)	15 Participants	13 Participants

SECONDARY outcome

Timeframe: Week 24

Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.

Outcome measures

Outcome measures
Measure	Brodalumab n=23 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=15 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
PSI Total Score of 0 at Week 24	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed.

Outcome measures

Outcome measures
Measure	Brodalumab n=64 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=33 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Number of Symptom-free Days From Randomisation to Week 24	0.44 days Standard Deviation 0.8	0.42 days Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Not all participants had recorded PSI data, therefore the analysed number of participants is lower than the randomised number of participants.

Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms.

Outcome measures

Outcome measures
Measure	Brodalumab n=83 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=78 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Burden of Symptoms	6.00 score on a scale Standard Error 0.54	10.92 score on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline to Week 24

DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

Outcome measures

Outcome measures
Measure	Brodalumab n=99 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=86 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score	-16.67 score on a scale Standard Error 0.61	-14.10 score on a scale Standard Error 0.70

SECONDARY outcome

Timeframe: Week 24

DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

Outcome measures

Outcome measures
Measure	Brodalumab n=105 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=105 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
DLQI Total Score of 0 or 1 at Week 24	70 Participants	27 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

Population: Only participants with nail involvement at baseline were included in the analysis. Therefore the number of analysed participants differs from the number of randomised participants.

The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: * Pitting. * Leukonychia. * Red spots in lunula. * Nail plate crumbling. * Oil drop (salmon patch) discoloration. * Onycholysis. * Nail bed hyperkeratosis. * Splinter haemorrhages. A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection.

Outcome measures

Outcome measures
Measure	Brodalumab n=43 Participants Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Fumaric Acid Esters n=38 Participants Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Change From Baseline at Week 24 in NAPSI Total Score	-2.97 score on a scale Standard Error 0.54	-1.26 score on a scale Standard Error 0.57

Adverse Events

Brodalumab 210 mg

Serious events: 3 serious events

Other events: 66 other events

Deaths: 0 deaths

Fumaric Acid Ester

Serious events: 1 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brodalumab 210 mg n=104 participants at risk Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).	Fumaric Acid Ester n=102 participants at risk Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) \> Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.
Gastrointestinal disorders Crohn's disease	0.00% 0/104 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.98% 1/102 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Gastrointestinal disorders Reactive gastropathy	0.96% 1/104 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.00% 0/102 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.96% 1/104 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.00% 0/102 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.96% 1/104 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.00% 0/102 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.

Other adverse events

Additional Information

Clinical Disclosure

LEO Pharma AS

Phone: (+1) 877-557-1168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigators have agreed to refrain from publishing based on data from this trial until the multi-center publication containing data from all sites has been published (usually after approx. 18 months). After this, any publication by individual investigators must be reviewed by the sponsor prior to submission. Sponsor has the right to remove any commercially confidential information and/or delay the publication up to 4 months to allow time for activities protecting intellectual rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Brodalumab 210 mg n=104 participants at risk Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).	Fumaric Acid Ester n=102 participants at risk Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) \> Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.
Blood and lymphatic system disorders Lymphopenia	1.9% 2/104 • Number of events 3 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	13.7% 14/102 • Number of events 14 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Gastrointestinal disorders Abdominal pain	1.9% 2/104 • Number of events 2 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	10.8% 11/102 • Number of events 13 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Gastrointestinal disorders Abdominal pain upper	1.9% 2/104 • Number of events 2 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	27.5% 28/102 • Number of events 43 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Gastrointestinal disorders Diarrhoea	3.8% 4/104 • Number of events 4 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	57.8% 59/102 • Number of events 77 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Gastrointestinal disorders Nausea	5.8% 6/104 • Number of events 7 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	8.8% 9/102 • Number of events 13 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
General disorders Fatigue	4.8% 5/104 • Number of events 6 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	5.9% 6/102 • Number of events 8 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Infections and infestations Viral upper respiratory tract infection	33.7% 35/104 • Number of events 41 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	20.6% 21/102 • Number of events 24 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Injury, poisoning and procedural complications Overdose	7.7% 8/104 • Number of events 8 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.00% 0/102 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Musculoskeletal and connective tissue disorders Arthralgia	8.7% 9/104 • Number of events 10 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	3.9% 4/102 • Number of events 4 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Musculoskeletal and connective tissue disorders Back pain	5.8% 6/104 • Number of events 6 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.98% 1/102 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Nervous system disorders Headache	12.5% 13/104 • Number of events 27 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	11.8% 12/102 • Number of events 19 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Psychiatric disorders Depressive symptom	4.8% 5/104 • Number of events 5 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	6.9% 7/102 • Number of events 7 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 6/104 • Number of events 6 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	0.98% 1/102 • Number of events 1 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Skin and subcutaneous tissue disorders Pruritus	5.8% 6/104 • Number of events 6 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	2.0% 2/102 • Number of events 2 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Vascular disorders Flushing	0.00% 0/104 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.	28.4% 29/102 • Number of events 40 • From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.