Trial Outcomes & Findings for A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly (NCT NCT01198132)

NCT ID: NCT01198132

Last Updated: 2017-12-14

Results Overview

The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

2 years post treatment (IMP) administration

Results posted on

2017-12-14

Participant Flow

A total of 129 subjects were randomized. Out of which 126 subjects treated in the study and 90 subjects completed the study.

Participant milestones

Participant milestones
Measure	Cholecalciferol Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Study STARTED	63	66
Overall Study COMPLETED	45	45
Overall Study NOT COMPLETED	18	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Cholecalciferol Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Study Withdrawal by Subject	4	5
Overall Study Physician Decision	5	4
Overall Study Other Unspecified	3	6
Overall Study Lack of Efficacy	2	3
Overall Study Sign/symptoms of underlying disease	2	1
Overall Study Abnormal/clinically significant biologic	1	1
Overall Study Adverse Event	0	1
Overall Study Protocol Violation	1	0

Baseline Characteristics

A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.	Total n=129 Participants Total of all reporting groups
Age, Continuous	38.5 years STANDARD_DEVIATION 9.29 • n=5 Participants	36.9 years STANDARD_DEVIATION 8.34 • n=7 Participants	37.7 years STANDARD_DEVIATION 8.81 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	39 Participants n=7 Participants	89 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	27 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects.

The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years).

Outcome measures

Outcome measures
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Annualized Relapse Rate	0.45 Relapse per year Interval 0.2 to 0.69	0.34 Relapse per year Interval 0.22 to 0.46

SECONDARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.

Time to First Documented Relapse was calculated using Kaplan-Meier survival methods.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=61 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=65 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Time to First Documented Relapse	NA weeks Median and Confidence interval could not be calculated due to a limited number of events .	NA weeks Interval 60.1 to Median and Confidence interval could not be calculated due to a limited number of events .

SECONDARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects.

Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Mean and standard deviation were reported.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Mean Number of Relapses Per Subject	0.5 relapses Standard Deviation 0.78	0.5 relapses Standard Deviation 0.75

SECONDARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects. Here "Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure.

The relapse-free patients after 2 years of treatment was calculated using Cochran-Mantel-Haenszel test using the site as control variable.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=45 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=46 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Number of Relapse-Free (Documented) Subjects	35 subjects	27 subjects

SECONDARY outcome

Timeframe: Baseline up to week 96

Population: ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.

Disability progression was assessed using Expanded disability status scale (EDSS). EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A one-point increase on the EDSS scale was considered as a progression in disability. The time to disability progression was summarized using Kaplan-Meier survival methods. The cumulative probability of confirmed disease progression at each visit was obtained by applying a Kaplan-Meier method to the time to confirmed disease progression.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=60 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=65 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Cumulative Probability of Progression of Disability (Kaplan-Meier Curves)	12.7 percentage of subjects	9.1 percentage of subjects

SECONDARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=44 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=41 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI) T1-weighted MRI	0.4 lesions Standard Deviation 0.76	1.9 lesions Standard Deviation 3.76
Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI) T2-weighted MRI	0.5 lesions Standard Deviation 0.79	2.0 lesions Standard Deviation 4.71

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: ITT set included all randomized subjects. Here "n" signifies those subjects who were evaluable for this outcome measure at the specified time points.

Baseline defined as last value recorded prior to first intake of study drug.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Changes From Baseline in Measured Lesion Load (T2) Baseline (n=49, 43)	5305.4 cubic millimeter (mm^3) Standard Deviation 10858.86	3520.1 cubic millimeter (mm^3) Standard Deviation 4954.44
Changes From Baseline in Measured Lesion Load (T2) Change at Week 96 (n=44, 38)	-315.0 cubic millimeter (mm^3) Standard Deviation 2523.97	596.3 cubic millimeter (mm^3) Standard Deviation 2034.80

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: ITT set included all randomized subjects.

The Adapted Paced Auditory Serial Addition Task (PASAT) is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The total score for PASAT is the total number of correct answers (out of 60, for a total possible score ranging from 0-60 with higher score indicates higher auditory processing speed) for each trial. Change from baseline in PASAT total score at Week 96 was summarized.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96 Baseline	39.9 units on a scale Standard Deviation 14.80	43.3 units on a scale Standard Deviation 12.49
Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96 Change at Week 96	6.4 units on a scale Standard Deviation 8.49	6.0 units on a scale Standard Deviation 8.02

SECONDARY outcome

Timeframe: 2 years post treatment (IMP) administration

Population: ITT set included all randomized subjects.

The EQ-5D health questionnaire is a generic self-reported health-related quality of life instrument that includes a 100 mm Visual Analog Scale (VAS) to measure the general health state, as well as 5 items corresponding to one dimension each: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, the VAS scale is not collected and the version 3L of the scale was used: Each dimension had 3 possible levels: 1 = no problem, 2 = some problems and 3 = extreme problems. EQ-5D-3L weighted health state index exists that combines the score of the 5 dimensions and ranges from 0 to 1 (full health). The variables for the 5 dimensions of the EQ-5D descriptive system was named 'mobility','selfcare', 'activity', 'pain', and 'anxiety'. The 5 variables contained the values for the different dimensions in the EQ-5D health profile (i.e. 1, 2, or 3).

Outcome measures

Outcome measures
Measure	Cholecalciferol n=63 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=66 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Baseline (n=60, 63)	0.7834 units on a scale Standard Deviation 0.24090	0.7937 units on a scale Standard Deviation 0.21447
Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Change at Week 96 (n=43, 45)	-0.0051 units on a scale Standard Deviation 0.13742	0.0043 units on a scale Standard Deviation 0.19654

SECONDARY outcome

Timeframe: Baseline up to end of treatment (week 96)

Population: Safety set included all subjects who receive at least one administration of trial medication.

A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect and TEAE was defined as newly occurring or worsening after first dose. Clinical laboratory abnormalities are expected to be reported as adverse events if they met any criterion for seriousness, led to treatment discontinuation, required a medical intervention or were considered clinically significant by the investigator.

Outcome measures

Outcome measures
Measure	Cholecalciferol n=61 Participants Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=65 Participants Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory TEAEs	43 subjects	35 subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory Serious TEAEs	11 subjects	10 subjects

Adverse Events

Cholecalciferol

Serious events: 11 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Title: Merck KGaA Communication Center

Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first publication will be publication of results of the analysis of primary endpoint(s) that will include data from all trial centers. Any publications and presentations of results, either in whole or in part, by investigators or their representatives will require pre-submission review by the sponsor/CRO. Sponsor will not suppress or veto publications, but maintains right to delay publication in order to protect intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cholecalciferol n=61 participants at risk Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.	Placebo n=65 participants at risk Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Cardiac disorders Stress cardiomyopathy	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Gastrointestinal disorders Abdominal pain	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Gastrointestinal disorders Gastritis	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Infections and infestations Appendicitis	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Infections and infestations Abdominal abscess	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Injury, poisoning and procedural complications Foot fracture	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Nervous system disorders Epilepsy	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Pregnancy, puerperium and perinatal conditions Pregnancy on contraceptive	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Pregnancy, puerperium and perinatal conditions Pregnancy on oral contraceptive	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Pregnancy, puerperium and perinatal conditions Pregnancy after post coital contraception	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Pregnancy, puerperium and perinatal conditions Foetal death	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Surgical and medical procedures Abortion induced complete	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Surgical and medical procedures Plastic surgery to the face	1.6% 1/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	0.00% 0/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Endocrine disorders Adrenal mass	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Renal and urinary disorders Nephrolithiasis	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/61 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.	1.5% 1/65 • Baseline till the end of the study (week 96) Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.