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UNDERSTANDING THE DIFFERENCE
Clinical Trials VS Clinical Practice
In order to better predict the occurrence of infusion reactions, a post hoc analysis of the pivotal clinical trials was completed. This led to the development of the KRYSTEXXA Monitoring Protocol.
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Sign up nowUNDERSTANDING THE SAFETY DATA
FROM PIVOTAL CLINICAL TRIALS TO CLINICAL PRACTICE
Pivotal clinical trials: double-blind protocol masked the causes leading to higher infusion reaction risk1,2
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During the pivotal clinical trials, the relationship between sUA levels, anti-drug antibodies and infusion reactions was unknown, and therefore not observed1,2
- Anti-drug antibodies are common to biologic therapies3
- Identifying the development of anti-drug antibodies is often difficult4
- Anti-drug antibodies can lead to decreased efficacy and an increased risk of infusion reactions3
- In the pivotal clinical trials, an sUA >6 mg/dL often reflected the development of anti-drug antibodies to pegloticase2,5
Because of the double-blind protocol, all patients received all doses of KRYSTEXXA regardless of anti-drug antibody formation or sUA level increases1
POST HOC ANALYSIS: UNCOVERING THE LINK BETWEEN ANTI-DRUG ANTIBODIES, sUA LEVELS, LOSS OF RESPONSE, AND RISK OF INFUSION REACTIONS
- 20/22 patients who experienced infusion reactions had an sUA level >6 mg/dL1,2
- All patients experienced an initial drop in sUA. Patients whose sUA began to rebound to >6 mg/dL had formed meaningful anti-drug antibodies1,2,6
- These anti-drug antibodies caused accelerated clearance of pegloticase, leading to a reduced systemic pegloticase level, loss of uric acid lowering effect, and a higher risk of infusion reactions1,2,6
This makes sUA an accurate biomarker to help predict an increased likelihood of infusion reactions
sUA LEVELS THROUGHOUT THE 6-MONTH PIVOTAL CLINICAL TRIALS5,6
UNDERSTANDING THE SAFETY DATA
FROM PIVOTAL CLINICAL TRIALS TO CLINICAL PRACTICE
Close monitoring of sUA within 48 hours prior to the infusion can significantly reduce infusion reactions1
KRYSTEXXA Monitoring Protocol: sUA can help identify patients at risk for infusion reactions1,6,7
sUA: A BIOMARKER THAT INFORMS THE SAFETY AND EFFICACY OF KRYSTEXXA IN CLINICAL PRACTICE
Adapted with permission from Baraf HS et al. J Clin Rheumatol. 2014;20(8):427-432.
*Based on infusion reactions per patient.2
TYPES OF INFUSION REACTIONS IN THE PIVOTAL CLINICAL TRIALS
| INFUSION REACTIONS | Frequency (%) |
|---|---|
| Hives | 10.6 |
| Chest discomfort | 9.5 |
| Chest pain | 9.5 |
| Reddening of the skin | 9.5 |
| Itching of the skin | 9.5 |
| Difficulty breathing | 7.1 |
The majority of infusion reactions in the pivotal clinical trials were resolved by slowing or interrupting the infusion and restarting at the same or a slower rate2†
†Approximately 75% of infusion reactions with a recorded intervention.2
SEVERITY OF INFUSION REACTIONS IN THE PIVOTAL CLINICAL TRIALS2‡
Incidence of infusion reactions by severity in the randomized controlled trials (RCT)
| INFUSION REACTION SEVERITY |
PEGLOTICASE BIWEEKLY (n=85) n (%) |
PLACEBO (n=43§) n (%) |
|---|---|---|
| Mild | 7 (8) | 0 |
| Moderate | 11 (13) | 2 (5) |
| Severe | 4 (5) | 0 |
These 4 cases of severe infusion reactions identified by investigators were retrospectively reclassified as anaphylaxis by the FDA (n=85)2
‡Only the most severe episode is showing if a patient had more than 1 event.2
§Thirty-nine of these patients entered the OLE study and were treated with pegloticase.2
CHARACTERIZATION OF SEVERE INFUSION REACTIONS: ALL WERE RESOLVED ON SITE2
| PATIENT | INFUSION REACTIONS | TREATMENT | OUTCOME |
|---|---|---|---|
| PATIENT 1 | INFUSION REACTIONSDifficulty breathing, swelling of the tongue |
TREATMENT
Infusion discontinued (Benadryl®: 25 mg IV) |
OUTCOME Infusion reaction resolved |
| PATIENT 2 | INFUSION REACTIONS Difficulty breathing, hives, elevated heart rate, elevated blood pressure |
TREATMENT
Infusion discontinued (Benadryl®, Ventolin®) |
OUTCOME Infusion reaction resolved |
| PATIENT 3 | INFUSION REACTIONS Flushing, itchy skin, low blood pressure, elevated heart rate, hives‖ |
TREATMENT
Infusion discontinued (Benadryl®, Demerol®) |
OUTCOME Infusion reaction resolved |
| PATIENT 4 | INFUSION REACTIONS Itchy eye, puffy eye, chest discomfort, throat irritation, joint pain, back pain | TREATMENT Infusion discontinued | OUTCOME Infusion reaction resolved |
‖Patient did not take full premedication regimen.2
Of the 4 cases reclassified as anaphylaxis, 3 likely would have been prevented using the KRYSTEXXA Monitoring Protocol
In the pivotal clinical trials, no patients with infusion reactions required intubation, mechanical ventilator support, or hospitalization. There were no infusion-related deaths
Get more information on the KRYSTEXXA Monitoring Protocol
Members of the KRYSTEXXA team in your area are available to answer your questions.
References
- Keenan RT, et al. Rheumatol Ther. 2019;6:299-304.
- Baraf HSB, et al. J Clin Rheumatol. 2014;20:427-432.
- Strand V, et al. BioDrugs. 2017;31:299-316.
- Lombardi G, et al. BMJ Open. 2016;6:1-7.
- Sundy JS, et al. JAMA. 2011;306:711-720.
- KRYSTEXXA (pegloticase) [prescribing information] Horizon.
- Data on file. Horizon, September 2016.
- Data on file. Horizon, May 2017.