Trial Outcomes & Findings for A Study of Certolizumab Pegol as Additional Therapy in Chinese Patients With Active Rheumatoid Arthritis (NCT NCT02151851)

Last Updated: 2018-06-28

Results Overview

The assessments are based on a 20 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 20 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

430 participants

Primary outcome timeframe

Week 24

Results posted on

2018-06-28

Participant Flow

The study started to enroll patients in July 2014 and concluded in June 2016.

Participant Flow refers to the Randomized Set.

Participant milestones

Participant milestones
Measure	Placebo + Methotrexate Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Study STARTED	114	316
Overall Study Included in the Safety Set	113	316
Overall Study COMPLETED	38	186
Overall Study NOT COMPLETED	76	130

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Methotrexate Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Study Lack of Efficacy	67	94
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	2	5
Overall Study Medical impairment	1	0
Overall Study Low compliance to study visits	0	1
Overall Study Subject entered into study in error	0	1
Overall Study Adverse Event	6	28

Baseline Characteristics

A Study of Certolizumab Pegol as Additional Therapy in Chinese Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Methotrexate n=113 Participants Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate n=316 Participants Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Total Title n=429 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	107 Participants n=5 Participants	298 Participants n=7 Participants	405 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants
Age, Continuous	47.1 years STANDARD_DEVIATION 11.1 • n=5 Participants	48.2 years STANDARD_DEVIATION 11.8 • n=7 Participants	47.9 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	268 Participants n=7 Participants	363 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	48 Participants n=7 Participants	66 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study medication administration and provided any efficacy data after the first administration. NRI = non-responder imputation.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (FAS) n=113 Participants Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (FAS) n=312 Participants Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 24	23.9 percentage of participants	54.8 percentage of participants

SECONDARY outcome

Timeframe: Week 24

The assessments are based on a 50 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 50 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (FAS) n=113 Participants Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (FAS) n=312 Participants Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 24	7.1 percentage of participants	36.5 percentage of participants

SECONDARY outcome

Timeframe: Week 24

The assessments are based on a 70 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 70 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (FAS) n=113 Participants Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (FAS) n=312 Participants Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 24	2.7 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. Each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3. A total score is computed from the item scores using the scoring rules provided by the index's author. HAQ-DI scores range from 0 to 3. Lower scores indicate less disability. Negative values indicate improvement from Baseline.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (FAS) n=110 Participants Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (FAS) n=306 Participants Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24	-0.185 units on a scale Standard Deviation 0.463	-0.530 units on a scale Standard Deviation 0.589

Adverse Events

Placebo + Methotrexate (SS)

Serious events: 3 serious events

Other events: 48 other events

Deaths: 0 deaths

Certolizumab Pegol + Methotrexate (SS)

Serious events: 20 serious events

Other events: 130 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo + Methotrexate (SS) n=113 participants at risk Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (SS) n=316 participants at risk Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Blood and lymphatic system disorders Anaemia	6.2% 7/113 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	5.4% 17/316 • Number of events 19 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	13.3% 15/113 • Number of events 21 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	15.8% 50/316 • Number of events 60 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Latent tuberculosis	6.2% 7/113 • Number of events 7 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	7.6% 24/316 • Number of events 24 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Urinary tract infection	6.2% 7/113 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	4.1% 13/316 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Liver function test abnormal	3.5% 4/113 • Number of events 6 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	7.0% 22/316 • Number of events 24 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Alanine aminotransferase increased	7.1% 8/113 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	6.0% 19/316 • Number of events 26 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations White blood cell count decreased	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	5.7% 18/316 • Number of events 24 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Aspartate aminotransferase increased	6.2% 7/113 • Number of events 8 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	5.1% 16/316 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Neutrophil count increased	7.1% 8/113 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	1.9% 6/316 • Number of events 6 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Lymphocyte count decreased	7.1% 8/113 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.

Additional Information

UCB

Cares

Phone: +1844 599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo + Methotrexate (SS) n=113 participants at risk Subjects will receive Placebo (1mL / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Certolizumab Pegol + Methotrexate (SS) n=316 participants at risk Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe \[PFS\], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Blood and lymphatic system disorders Anaemia	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Cardiac disorders Aortic valve incompetence	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Cardiac disorders Cardiac arrest	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Gastric ulcer	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Gastritis	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Ascites	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Hepatobiliary disorders Cholecystitis chronic	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.00% 0/316 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Hepatobiliary disorders Cholelithiasis	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.00% 0/316 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Hepatobiliary disorders Liver injury	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Hepatobiliary disorders Bile duct stone	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.00% 0/316 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Immune system disorders Anaphylactic shock	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Pneumonia	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Pulmonary tuberculosis	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Pericarditis tuberculous	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Infections and infestations Tuberculous pleurisy	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Investigations Protein urine present	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.00% 0/316 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Nervous system disorders Subarachnoid haemorrhage	0.88% 1/113 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.00% 0/316 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Renal and urinary disorders Haematuria	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.32% 1/316 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/113 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.	0.63% 2/316 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25. Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.