Trial Outcomes & Findings for Effect of Diacerein vs Celecoxib on Symptoms and Structural Changes in Symptomatic Knee Osteoarthritis (NCT NCT02688400)

NCT ID: NCT02688400

Last Updated: 2023-12-01

Results Overview

Change form baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) A pain subscale after 182 days of treatment. WOMAC A pain subscale: 0 - 50 cm; 50 = worse

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 380 participants
• Primary outcome timeframe: baseline and 182 days
• Results posted on: 2023-12-01

Participant Flow

Participant milestones

Measure	Diacerein One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo	Celecoxib One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Overall Study STARTED	187	193
Overall Study COMPLETED	141	149
Overall Study NOT COMPLETED	46	44

Reasons for withdrawal

Measure	Diacerein One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo	Celecoxib One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Overall Study Protocol Violation	2	5
Overall Study Lack of Efficacy	7	7
Overall Study Adverse Event	21	12
Overall Study Withdrawal by Subject	15	13
Overall Study No study medication intake	1	4
Overall Study Lost to Follow-up	0	3

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Diacerein n=187 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo	Celecoxib n=193 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo	Total n=380 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=187 Participants	0 Participants n=193 Participants	0 Participants n=380 Participants
Age, Categorical Between 18 and 65 years	106 Participants n=187 Participants	97 Participants n=193 Participants	203 Participants n=380 Participants
Age, Categorical >=65 years	81 Participants n=187 Participants	96 Participants n=193 Participants	177 Participants n=380 Participants
Age, Continuous	63.7 years STANDARD_DEVIATION 6.3 • n=187 Participants	64.4 years STANDARD_DEVIATION 7.0 • n=193 Participants	64.1 years STANDARD_DEVIATION 6.7 • n=380 Participants
Sex: Female, Male Female	137 Participants n=187 Participants	146 Participants n=193 Participants	283 Participants n=380 Participants
Sex: Female, Male Male	50 Participants n=187 Participants	47 Participants n=193 Participants	97 Participants n=380 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Canada	80 participants n=187 Participants	79 participants n=193 Participants	159 participants n=380 Participants
Region of Enrollment Austria	3 participants n=187 Participants	6 participants n=193 Participants	9 participants n=380 Participants
Region of Enrollment Belgium	2 participants n=187 Participants	1 participants n=193 Participants	3 participants n=380 Participants
Region of Enrollment Czechia	59 participants n=187 Participants	63 participants n=193 Participants	122 participants n=380 Participants
Region of Enrollment Spain	43 participants n=187 Participants	44 participants n=193 Participants	87 participants n=380 Participants
Study Knee Right knee	87 participants n=187 Participants	96 participants n=193 Participants	183 participants n=380 Participants
Study Knee Left knee	100 participants n=187 Participants	97 participants n=193 Participants	197 participants n=380 Participants

PRIMARY outcome

Timeframe: baseline and 182 days

Population: The Per Protocol Set (PPS) was a subset of the ITT and included all patients who did not present any major deviation of the protocol over the 6-month follow-up period. These deviations were detected during the blind review meeting.

Change form baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) A pain subscale after 182 days of treatment.

WOMAC A pain subscale: 0 - 50 cm; 50 = worse

Outcome measures

Measure	Diacerein n=140 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=148 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change Form Baseline in WOMAC A Pain Subscale	-11.14 cm Standard Error 0.91	-11.82 cm Standard Error 0.89

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-to-treat

Absolute Changes from Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) after 182 days of treatment.

WOMAC scale: 0 - 240 cm; 240 = worse - Intention-To-Treat (N=370) Pain subscale: 0-50cm; 50 = worse; Stifness subscale: 0-20cm; 20 = worse; Function subscale: 0-170cm; 170 = worse Absolute changes in WOMAC scores: <0 = improvement; 0 = stable; >0 = worsening

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in WOMAC OA Scores Total Score	-41.0 score Standard Deviation 53.1	-42.9 score Standard Deviation 55.0
Change From Baseline in WOMAC OA Scores Pain Score	-10.03 score Standard Deviation 11.95	-9.60 score Standard Deviation 12.02
Change From Baseline in WOMAC OA Scores Stiffness Score	-3.56 score Standard Deviation 4.99	-3.99 score Standard Deviation 5.32
Change From Baseline in WOMAC OA Scores Physical Function Score	-27.2 score Standard Deviation 39.0	-29.3 score Standard Deviation 39.8

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-to-treat

Absolute Changes from Baseline in Pain Visual Analogue Scale (VAS): 0-10 cm; 10 = worse

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Absolute Changes From Baseline in Pain Visual Analogue Scale	-2.34 score Standard Deviation 2.55	-2.46 score Standard Deviation 2.61

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intentio-to-treat

Osteoarthritis Research Society International (OARSI) Responders

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
OARSI Responders	99 Participants	97 Participants

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intent-to-treat

Assessment of Joint Swelling, joint Effusion or Both

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Assessment of Joint Swelling, Effusion or Both Joint Swelling	47 participants	48 participants
Assessment of Joint Swelling, Effusion or Both Joint Effusion	37 participants	37 participants
Assessment of Joint Swelling, Effusion or Both Joint Swelling and Effusion	19 participants	23 participants

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-to-treat

Overall Daily number of tablets taken during the 6 month study

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Consumption of Acetaminophen	1.06 tablets Standard Deviation 1.75	0.91 tablets Standard Deviation 1.02

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-to-treat

Change from baseline in global assessment of disease activity was assessed using a VAS scale (0-10cm; 10=worse)

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in Patient's Global Assessment of Disease Activity Patient's Global Assessment	-1.81 score Standard Deviation 2.79	-1.97 score Standard Deviation 2.97
Change From Baseline in Patient's Global Assessment of Disease Activity Investigator's Global Assessment	-2.02 score Standard Deviation 2.55	-2.65 score Standard Deviation 2.55

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-To-Treat

Between group comparison in Patient's and Investigator's Global Assessment of Response to Therapy using a 0-10 cm disease activity VAS scale: 0 cm = very well; 10 cm = very poorly

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Global Assessment of Response to Therapy Patient's Global Assessement	3.89 score on a scale Standard Deviation 2.57	3.61 score on a scale Standard Deviation 2.52
Global Assessment of Response to Therapy Investigator's Global Assessment	3.85 score on a scale Standard Deviation 2.51	3.35 score on a scale Standard Deviation 2.42

SECONDARY outcome

Timeframe: Day 182 or early termination

Population: Intention-To-Treat

Absolute Changes from Baseline in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Quality of Life questionnaire SF-36. Scale range for each component (PCS and MCS): minimum = 0, maximum = 100, with higher scores indicating better quality of life. Absolute changes in each component (PCS and MCS): >0 = improvement; 0 = stable; <0 = worsening.

Outcome measures

Measure	Diacerein n=183 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=187 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Quality of Life SF-36 Physical Component Summary	2.46 score on a scale Standard Deviation 6.74	4.57 score on a scale Standard Deviation 8.08
Quality of Life SF-36 Mental Component Summary	1.56 score on a scale Standard Deviation 8.34	-0.14 score on a scale Standard Deviation 8.87

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Relative cartilage volume loss from baseline in the medial compartment of the knee using MRI

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Cartilage Volume Loss From Baseline in the Medial Compartment Using MRI	-4.8 percentage of volume loss Standard Deviation 6.3	-6.0 percentage of volume loss Standard Deviation 6.7

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Relative cartilage volume loss from baseline in the lateral compartment of the knne using MRI

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Cartilage Volume Loss From Baseline in the Lateral Compartment Using MRI	-4.4 percentage of volume loss Standard Deviation 4.4	-4.1 percentage of volume loss Standard Deviation 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Absolute Change from baseline in synovitis (synovial membrane thickness) in the global knee using MRI

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in Synovitis (Synovial Membrane Thickness) Using MRI	0.24 mm Standard Deviation 0.18	0.27 mm Standard Deviation 0.15

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Relative mean change from baseline in WOMAC Pain subscore

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in WOMAC A Pain Subscale	-26.2 percentage of change in WOMAC Pain score Standard Deviation 48.0	-37.1 percentage of change in WOMAC Pain score Standard Deviation 52.2

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Relative Change from baseline in global stiffness using WOMAC subscale

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in Global Stiffness Using WOMAC Subscale	-24.3 percentage of change in WOMACStifness sc Standard Deviation 46.6	-38.1 percentage of change in WOMACStifness sc Standard Deviation 44.5

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 728 days

Population: Exploratory ITT

Relative change from baseline in Visual Analogue Scale pain (VAS-Huskisson's)

Outcome measures

Measure	Diacerein n=26 Participants One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo ITT (n=	Celecoxib n=30 Participants One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Change From Baseline in Visual Analogue Scale Pain (VAS-Huskisson's)	-31.4 Percentage of change in VAS score Standard Deviation 43.8	-37.6 Percentage of change in VAS score Standard Deviation 44.4

Adverse Events

Diacerein

Serious events: 3 serious events

Other events: 49 other events

Deaths: 0 deaths

Celecoxib

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Diacerein n=186 participants at risk One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo	Celecoxib n=190 participants at risk One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Vascular disorders Temporal arteritis	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Investigations Gamma-glutamyltransferase increased	0.54% 1/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Investigations Transaminases increased	0.54% 1/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm prostate	0.54% 1/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Nervous system disorders Cerebrovascular accident	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Abdominal pain	0.54% 1/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Psychiatric disorders Depression	0.54% 1/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.

Other adverse events

Measure	Diacerein n=186 participants at risk One placebo capsule once daily in the morning (breakfast) and one diacerein 50 mg capsule once daily in the evening (dinner) for the first month, then diacerein capsules twice daily with meals in the morning (breakfast) and the evening (dinner). Diacerein Placebo	Celecoxib n=190 participants at risk One celecoxib 200 mg capsule once daily in the morning (breakfast) and one placebo capsule once daily in the evening (dinner). Celecoxib Placebo
Gastrointestinal disorders Abdominal pain	3.2% 6/186 • Number of events 7 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	1.1% 2/190 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Abdominal pain upper	2.2% 4/186 • Number of events 4 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Chromaturia	2.7% 5/186 • Number of events 5 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Constipation	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Diarrhoea	10.2% 19/186 • Number of events 21 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	3.7% 7/190 • Number of events 7 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Dyspepsia	2.7% 5/186 • Number of events 5 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	2.6% 5/190 • Number of events 5 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Epigastric discomfort	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Faeces soft	1.6% 3/186 • Number of events 3 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	3.2% 6/190 • Number of events 6 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Flatulence	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Frequent bowel movements	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Gastritis	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Haematuria	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Nausea	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	1.1% 2/190 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Paraesthesia oral	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Tongue geographic	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Toothache	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Gastrointestinal disorders Vomiting	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
General disorders Asthenia	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
General disorders Chest pain	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
General disorders Fatigue	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Immune system disorders Seasonal allergy	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Infections and infestations Cardiac disorder	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Infections and infestations Labyrinthitis	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Infections and infestations Nasopharyngitis	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Infections and infestations Palpitations	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Infections and infestations Tooth infection	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Injury, poisoning and procedural complications Fall	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Investigations Alanine aminotransferase increased	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Investigations Blood pressure increased	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Investigations Platelet count decreased	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Musculoskeletal and connective tissue disorders Back pain	1.1% 2/186 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Nervous system disorders Dizziness	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Nervous system disorders Headache	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	1.6% 3/190 • Number of events 4 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Psychiatric disorders Libido decreased	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Skin and subcutaneous tissue disorders Rash	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	1.1% 2/190 • Number of events 2 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Skin and subcutaneous tissue disorders Rash pruritic	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Vascular disorders Hot flush	0.00% 0/186 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.53% 1/190 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.
Vascular disorders Hypertensive crisis	0.54% 1/186 • Number of events 1 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.	0.00% 0/190 • At each post-screening visit up to 2 years Of the 380 randomised patients, 4 patients did not receive at least one dose of study treatment. Thus the Safety Set was composed of 376 patients: 186 (99.5%) in the Diacerein group and 190 (98.4%) in the Celecoxib group.

Additional Information

Dr.Jean-Pierre Pelletier

Arthrolab inc.

Phone: +1 (514) 992-4939

Email: dr@jppelletier.ca

Results disclosure agreements

• Principal investigator is a sponsor employee All documents, data, know-how, formulae, and unused drugs provided to the Study Site or Investigator for purposes of the Study are and will remain the sponsor's (or its agent) property. The sponsor (or its agent) will have the right to use the results of the Study in any manner deemed appropriate to the sponsor's business interests. The sponsor will store information regarding the Study Site and Investigator in a database system, to be used for internal sponsor assessment purposes only.
• Publication restrictions are in place

Restriction type: OTHER