Arthritis, Juvenile Rheumatoid
Conditions
Keywords
Celecoxib, COX-2, NSAIDs, observational study, noninterventional study, cohort study, registry, epidemiologic study, pediatrics, rheumatology, phase iv study
Brief summary
This multi-center observational Registry will collect long-term safety data on patients treated with celecoxib or non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) as used in clinical practice for the treatment of Juvenile Idiopathic Arthritis (JIA).
Detailed description
None Study has been terminated early (LSLV = 09Jan2012) due to release of the postmarketing commitment by the US FDA. The study was stopped for futility/change in treatment paradigm that minimizes chronic NSAID use and not for safety concerns.
Interventions
DRUGCelecoxib
Non-interventional: Treatment assignment as per treating physician's judgement
DRUGnsNSAIDs
Non-interventional: Treatment assignment as per treating physician's judgement
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age at least 2 years but less than 18 years; JIA of any of the following subtypes: oligoarthritis, polyarthritis, or stable systemic disease; * new treatment (started not more than 6 months prior) with one NSAID (celecoxib or nsNSAID).
Exclusion criteria
* Patients with the following JIA subtypes: active systemic disease, psoriatic Arthritis, enthesitis-related Arthritis, or undifferentiated arthritis; * Patients with Reiter's syndrome; patients unlikely to complete 2 years of follow up; * Patients who need to use multiple NSAIDs at the same time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 2 years | Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs attributed to the NSAID (celecoxib or nsNSAID) utilized at time of event, regardless of the initial NSAID treatment at Registry entry. |
| JIA Concomitant Medications | Year 2 or early termination | JIA medications by class: GI protective agents (eg, proton-pump inhibitors, antacids, surcalfate), other GI, DMARDs, biologics, antihypertensives, NSAIDs (Celecoxib, Diclofenac, Ibuprofen, Meloxicam, Naproxen, other NSAIDs), corticosteroids (oral, IV, intra-articular, other forms), analgesics Acetaminophen, Opioids, other). Participants could receive more than 1 medication. |
Countries
United States
Participant flow
Pre-assignment details
A total of 275 people consented to participate in this study. One person should not have been enrolled and instead should have been a screen failure. This person did not receive any study drug.
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib Participants who were prescribed celecoxib at baseline per treating physician's judgment. Participants could switch to nonselective non-steroidal anti-inflammatory drugs (nsNSAIDs) at any time during the study. The use and dosage recommendations for celecoxib took place on the basis of the approved Product Label and were adjusted solely according to medical and therapeutic necessity. | 55 |
| nsNSAIDs Participants who were prescribed nsNSAIDs at baseline per treating physician's judgment. Any nsNSAID could be used at the discretion of the investigator, provided that the medicine was not contraindicated for the participant as per the current United States product information for that nsNSAID. Participants could switch to other nsNSAIDs or celecoxib at any time during the study. The use and dosage recommendations for study drug took place on the basis of the approved Product Label and were adjusted solely according to medical and therapeutic necessity. | 219 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insurance/cost of drug | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Unspecified, unrelated to AE/Toxicity | 2 | 7 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Total | nsNSAIDs | Celecoxib |
|---|---|---|---|
| Age, Customized 10-12 years | 59 Participants | 44 Participants | 15 Participants |
| Age, Customized 13-15 years | 42 Participants | 35 Participants | 7 Participants |
| Age, Customized 16-18 years | 19 Participants | 11 Participants | 8 Participants |
| Age, Customized 2-5 years | 85 Participants | 77 Participants | 8 Participants |
| Age, Customized 6-9 years | 69 Participants | 52 Participants | 17 Participants |
| Body Mass Index (BMI) | 17.55 kilograms per meter squared (kg/m^2) | 17.31 kilograms per meter squared (kg/m^2) | 17.70 kilograms per meter squared (kg/m^2) |
| Body weight | 30.90 kilogram (kg) | 30.20 kilogram (kg) | 33.60 kilogram (kg) |
| CHAQ - functioning | 0.52 Units on a scale STANDARD_DEVIATION 0.57 | 0.48 Units on a scale STANDARD_DEVIATION 0.54 | 0.65 Units on a scale STANDARD_DEVIATION 0.68 |
| CHAQ - pain | 0.75 Units on a scale STANDARD_DEVIATION 0.75 | 0.71 Units on a scale STANDARD_DEVIATION 0.72 | 0.92 Units on a scale STANDARD_DEVIATION 0.85 |
| Child Health Questionnaire (CHAQ) - global evaluation | 21.96 Units on a scale STANDARD_DEVIATION 23.56 | 20.15 Units on a scale STANDARD_DEVIATION 21.58 | 29.11 Units on a scale STANDARD_DEVIATION 29.34 |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Constipation | 21 Participants | 16 Participants | 5 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Diarrhea | 23 Participants | 18 Participants | 5 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Heartburn | 30 Participants | 21 Participants | 9 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Lower stomach pain | 50 Participants | 34 Participants | 16 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Missing | 4 Participants | 3 Participants | 1 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Nausea | 46 Participants | 32 Participants | 14 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems No problems | 155 Participants | 132 Participants | 23 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Poor appetite | 20 Participants | 13 Participants | 7 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Upper stomach pain | 26 Participants | 18 Participants | 8 Participants |
| Gastrointestinal Symptom Scale for Kids (GISSK) - Type of stomach problems Vomiting | 10 Participants | 8 Participants | 2 Participants |
| GISSK - severity of stomach problems | 14.0 Units on a scale STANDARD_DEVIATION 21.47 | 12.0 Units on a scale STANDARD_DEVIATION 19.84 | 21.9 Units on a scale STANDARD_DEVIATION 25.75 |
| Height | 132.00 centimeters (cm) | 130.10 centimeters (cm) | 141.30 centimeters (cm) |
| JIA medications Analgesics (Acetaminophen, Opioids, Other) | 27 Participants | 18 Participants | 9 Participants |
| JIA medications Antihypertensives | 5 Participants | 4 Participants | 1 Participants |
| JIA medications Biologics | 36 Participants | 28 Participants | 8 Participants |
| JIA medications Corticosteroids (Oral, IV, Intra-Articular) | 24 Participants | 19 Participants | 5 Participants |
| JIA medications Corticosteroids (Other) | 5 Participants | 3 Participants | 2 Participants |
| JIA medications Disease-modifying antirheumatic drugs (DMARDs) | 104 Participants | 83 Participants | 21 Participants |
| JIA medications Gastrointestinal (GI) protective agents | 66 Participants | 48 Participants | 18 Participants |
| JIA medications NSAIDs (Celecoxib) | 8 Participants | 0 Participants | 8 Participants |
| JIA medications NSAIDs (Diclofenac) | 0 Participants | 0 Participants | 0 Participants |
| JIA medications NSAIDs (Ibuprofen) | 9 Participants | 7 Participants | 2 Participants |
| JIA medications NSAIDs (Meloxicam) | 6 Participants | 6 Participants | 0 Participants |
| JIA medications NSAIDs (Naproxen) | 16 Participants | 16 Participants | 0 Participants |
| JIA medications NSAIDs (Other) | 5 Participants | 5 Participants | 0 Participants |
| JIA medications Other GI | 8 Participants | 4 Participants | 4 Participants |
| Juvenile Idiopathic Arthritis (JIA) Extended Oligoarticular | 14 Participants | 12 Participants | 2 Participants |
| Juvenile Idiopathic Arthritis (JIA) Missing | 1 Participants | 1 Participants | 0 Participants |
| Juvenile Idiopathic Arthritis (JIA) Persistent Oligoarticular | 146 Participants | 119 Participants | 27 Participants |
| Juvenile Idiopathic Arthritis (JIA) Poly RF- | 93 Participants | 70 Participants | 23 Participants |
| Juvenile Idiopathic Arthritis (JIA) Poly RF+ | 17 Participants | 14 Participants | 3 Participants |
| Juvenile Idiopathic Arthritis (JIA) Systemic | 3 Participants | 3 Participants | 0 Participants |
| Number of joints with active arthritis | 3.0 Joints STANDARD_DEVIATION 4.42 | 2.9 Joints STANDARD_DEVIATION 4.14 | 3.4 Joints STANDARD_DEVIATION 5.39 |
| Number of participants with abnormal physical exam results | 80 Participants | 63 Participants | 17 Participants |
| Participant or caregiver's assessment of participant's overall well-being | 2.9 Units on a scale STANDARD_DEVIATION 2.52 | 2.8 Units on a scale STANDARD_DEVIATION 2.5 | 3.2 Units on a scale STANDARD_DEVIATION 2.58 |
| Physician Global Assessment (PGA) of Disease Activity | 2.8 Units on a scale STANDARD_DEVIATION 2.22 | 2.9 Units on a scale STANDARD_DEVIATION 2.19 | 2.6 Units on a scale STANDARD_DEVIATION 2.36 |
| Sex: Female, Male Female | 212 Participants | 165 Participants | 47 Participants |
| Sex: Female, Male Male | 62 Participants | 54 Participants | 8 Participants |
| Weight and Height percentiles overall Height | 49.08 Percentile STANDARD_DEVIATION 30.63 | 50.70 Percentile STANDARD_DEVIATION 30.76 | 42.77 Percentile STANDARD_DEVIATION 29.59 |
| Weight and Height percentiles overall Weight | 54.76 Percentile STANDARD_DEVIATION 30.94 | 56.68 Percentile STANDARD_DEVIATION 30.96 | 47.22 Percentile STANDARD_DEVIATION 29.95 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 68 | 114 / 225 |
| serious Total, serious adverse events | 2 / 68 | 9 / 225 |
Outcome results
Primary
JIA Concomitant Medications
JIA medications by class: GI protective agents (eg, proton-pump inhibitors, antacids, surcalfate), other GI, DMARDs, biologics, antihypertensives, NSAIDs (Celecoxib, Diclofenac, Ibuprofen, Meloxicam, Naproxen, other NSAIDs), corticosteroids (oral, IV, intra-articular, other forms), analgesics Acetaminophen, Opioids, other). Participants could receive more than 1 medication.
Time frame: Year 2 or early termination
Population: Safety Analysis Set subset of participants who received JIA concomitant medications
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | JIA Concomitant Medications | GI protective agents | 20 Participants |
| Celecoxib | JIA Concomitant Medications | Other GI | 5 Participants |
| Celecoxib | JIA Concomitant Medications | DMARDs | 24 Participants |
| Celecoxib | JIA Concomitant Medications | Biologics | 13 Participants |
| Celecoxib | JIA Concomitant Medications | Antihypertensives | 1 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Celecoxib) | 7 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Diclofenac) | 0 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Ibuprofen) | 1 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Meloxicam) | 1 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Naproxen) | 0 Participants |
| Celecoxib | JIA Concomitant Medications | NSAIDs (Other) | 0 Participants |
| Celecoxib | JIA Concomitant Medications | Corticosteroids (oral, IV, intra-articular) | 4 Participants |
| Celecoxib | JIA Concomitant Medications | Corticosteroids (Other) | 2 Participants |
| Celecoxib | JIA Concomitant Medications | Analgesics (Acetaminophen, Opioids, Other) | 11 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Other) | 3 Participants |
| nsNSAIDs | JIA Concomitant Medications | GI protective agents | 54 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Ibuprofen) | 9 Participants |
| nsNSAIDs | JIA Concomitant Medications | Other GI | 8 Participants |
| nsNSAIDs | JIA Concomitant Medications | Corticosteroids (Other) | 6 Participants |
| nsNSAIDs | JIA Concomitant Medications | DMARDs | 102 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Meloxicam) | 8 Participants |
| nsNSAIDs | JIA Concomitant Medications | Biologics | 60 Participants |
| nsNSAIDs | JIA Concomitant Medications | Corticosteroids (oral, IV, intra-articular) | 15 Participants |
| nsNSAIDs | JIA Concomitant Medications | Antihypertensives | 4 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Naproxen) | 7 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Celecoxib) | 2 Participants |
| nsNSAIDs | JIA Concomitant Medications | Analgesics (Acetaminophen, Opioids, Other) | 19 Participants |
| nsNSAIDs | JIA Concomitant Medications | NSAIDs (Diclofenac) | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs attributed to the NSAID (celecoxib or nsNSAID) utilized at time of event, regardless of the initial NSAID treatment at Registry entry.
Time frame: Baseline up to 2 years
Population: Safety Analysis Set: participants who were prescribed at least one dose of any NSAID. Participants who switched treatment were counted for the NSAID utilized at the time of the event, regardless of the initial NSAID treatment at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 36 Participants |
| Celecoxib | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| nsNSAIDs | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 117 Participants |
| nsNSAIDs | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |