SJIA Safety Profile & Adverse Events
ACTEMRA Safety Profile in SJIA
Adverse events
  • The most common adverse events (AEs) (≥5%) seen in patients on ACTEMRA in the 12-week controlled portion of the study were upper respiratory tract infection, headache, nasopharyngitis, and diarrhea
Infections
Summary of infections
  • *Data from ongoing open-label extension over an average duration of 104 weeks of treatment.
  • The most commonly reported serious infections included pneumonia, gastroenteritis, varicella, and otitis media
Macrophage activation syndrome
  • In the 12-week controlled study, no patient in any treatment group experienced macrophage activation syndrome (MAS) while on assigned treatment
  • In an open-label, long-term extension study (N=112), 3 patients (3%) experienced MAS events. All 3 patients had ACTEMRA dose interrupted (2 patients) or discontinued (1 patient) for the MAS event, received treatment, and the MAS resolved without sequelae
  • Based on a limited number of cases, the incidence of MAS does not appear to be elevated in the ACTEMRA SJIA clinical development experience; however, no definitive conclusions can be made
Infusion reactions
  • In the 12-week controlled phase, patients were not routinely premedicated; however, most patients were on concomitant corticosteroids as part of their background treatment for SJIA
  • Infusion-related reactions were defined as all events occurring during or within 24 hours after an infusion
    • During infusion, 4% of patients on ACTEMRA and 0% of patients on placebo experienced events. One event (angioedema) was considered serious and life-threatening, and the patient was discontinued from study treatment
  • Within 24 hours after infusion, 16% of patients in the ACTEMRA treatment group and 5% of patients in the placebo group experienced an event. In the ACTEMRA group, events included rash, urticaria, diarrhea, epigastric discomfort, arthralgia, and headache. One of these events, urticaria, was considered serious
Immunogenicity

All 112 patients were tested for anti-tocilizumab antibodies at baseline. Two patients developed positive anti-tocilizumab antibodies: one of these patients experienced serious adverse events of urticaria and angioedema consistent with an anaphylactic reaction which led to withdrawal; the other patient developed MAS while on escape therapy and was discontinued from the study.

Laboratory Tests for Patients With SJIA

  • Decreases in neutrophils and platelets, and elevations in hepatic transaminases and lipids, were seen with ACTEMRA in clinical trials
  • Dose interruptions of ACTEMRA are recommended for liver enzyme abnormalities, low neutrophil counts, and low platelet counts in patients with SJIA. In SJIA, the decision to discontinue ACTEMRA for a laboratory abnormality should be based upon the medical assessment of the individual patient
Neutrophils
  • *Data from ongoing open-label extension over an average duration of 104 weeks of treatment.
  • There was no clear relationship between decreases in neutrophils <1 x 109/L and the occurrence of serious infections
  • Neutrophils should be monitored at the time of the second infusion and thereafter every 2 to 4 weeks
Platelets
  • *Data from ongoing open-label extension over an average duration of 104 weeks of treatment.
  • Decreases in platelets ≥100 x 103/μL were not associated with bleeding events
  • Platelets should be monitored at the time of the second infusion and thereafter every 2 to 4 weeks
Hepatic transaminases; CTC grades*
  • *Data presented are the highest ALT and AST elevations (by CTC grade) reported during study treatment for each patient.
  • †August 10, 2010 data cut.
  • ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal.
  • Concomitant MTX treatment did not affect elevations of ALT or AST ≥ 2.5x or ≥ 3x ULN.
  • In RA, elevations in transaminases did not result in apparent permanent or clinically evident hepatic injury in clinical trials.
  • ALT and AST levels should be monitored at the time of the second infusion and thereafter every 2 to 4 weeks. When clinically indicated, other liver function tests such as bilirubin should be considered
Lipids
  • *Data from 2-year TENDER study over an average duration of 104 weeks of treatment.
  •  
  • LDL-C=low-density lipoprotein cholesterol.
  • In the open-label extension study over an average duration of 73 weeks of treatment, the pattern and incidence of elevations in lipid parameters remained consistent with the 12-week controlled study data
  • Assessment of lipid parameters should be performed approximately 4 to 8 weeks following initiation of ACTEMRA therapy, then at approximately 24 week intervals
 
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DISCLAIMER:
By using this resource, you agree to the following: This Dosing Calculator is being provided “AS IS” and is intended for use only by qualified healthcare providers. All calculations should be confirmed before use. Genentech makes no claims as to the accuracy of the information contained herein. The information being provided is not a substitute for clinical judgment. Neither Genentech, nor any other party involved in the preparation or publication of this site shall be liable to you or others for any decisions made or actions taken by you or others in reliance on this information.
  • ACTEMRA should not be infused concomitantly in the same intravenous line with other drugs. ACTEMRA must be administered with an infusion set
  • Do not administer as an intravenous push or bolus
  • Dosing Calculator should not replace professional judgment or clinical experience. For additional dosing information please refer to the Dosing Guide
  • Doses exceeding 800 mg per infusion are not recommended
  • Dosing Calculator is not a substitute for medical examination. Please see Dosing Guide for more information
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