Download Use of Subcutaneous IgG in Patients on Concomitant

Use of Subcutaneous IgG in
Patients on Concomitant
Anticoagulant and Antiplatelet
Therapy
Mark R. Stein,1 Kelly Farnan,1 Danielle Eufrasio,1 Carla
Duff, 2 Jerry Hunter,3 Diana Ochoa,4 Marie-Claude
Levasseur,5 Loris Aro,6 Annette Zampelli7
1Allergy
Associates of the Palm Beaches, North Palm Beach, FL, USA; 2University
of South Florida, Tampa, FL, USA; 3Arizona Allergy Associates, Phoenix, AZ, USA;
4Allergy/Immunology Research Center of North Texas, Dallas, TX, USA; 5University
Health Center, Sainte-Justine Hospital, Montreal, QC, Canada; 6Toronto Allergy
Group, Toronto, ON, Canada; 7CSL Behring, LLC, King of Prussia, PA, USA
The International Nursing Group for Immunodeficiencies
October 3-6, 2012, Florence, Italy
Disclosures and Acknowledgments
• MRS has served as a speaker, consultant, and/or
investigator for Baxter Healthcare Corp, CSL Behring,
Merck, and Teva. CD, JH, MCL, and LA are nurse
consultants for CSL Behring. DO is a nurse consultant
for CSL Behring and has served on an advisory board
for Baxter Healthcare. AZ is employed by CSL
Behring.
• This presentation was supported by CSL Behring,
LLC.
• Medical writing and editorial support was provided by
Daniel McCallus, PhD, of Complete Publication
Solutions, LLC, and was funded by CSL Behring, LLC.
Introduction
• Primary or Secondary Immunodeficiency Disease
(PIDD/SIDD)
– Standard treatment:
• Intravenous immunoglobulin (IVIG)1
• Subcutaneous immunoglobulin (SCIG)1
• High prevalence of thrombotic risks in the general
population2
– Many patients with PIDD/SIDD are also prescribed
anticoagulant and antiplatelet (AC/AP) drugs for the
treatment and prophylaxis of thrombotic, cardiac, and
vascular diseases3
– Some disorders associated with PIDD have congenital
cardiovascular manifestations that require AC/AP
1. Fried AJ and Bonilla FA. Clin Microbiol Rev. 2009;22(3):396-414.
2. Heidenreich PA, et al. Circulation. 2011;123(8):933-944.
3. Alexander KP and Peterson ED. Circulation. 2010;121(17):1960-1970.
Rationale and Objective
• Rationale
– Infusion-site bleeding or bruising at the site of SCIG
administration due to the activity of AC/AP medication was
theoretical concern
• Objective
– To establish the safety of concomitant SCIG and AC/AP
therapy
Study Design
• Multicenter retrospective chart review of
tolerability data
• Patient inclusion criteria:
– PIDD or SIDD
– Receiving treatment with 20% SCIG
(Hizentra®, CSL Behring, LLC, King of
Prussia, PA) or 16% SCIG (Vivaglobin®, CSL
Behring, LLC; no longer available in the
United States)
– Prescribed concomitant AC/AP medications
Patient Descriptions
26 of the total 33
patients were part
of a larger (n=47)
retrospective
single-center study
on safety and
efficacy of SCIG in
the elderly
Parameter
Patients, n (%)
N=47
PIDD diagnosis
Hypogammaglobulinemia
29 (61.7)
IgG subclass deficiency or specific
antibody deficiency
9 (19.1)
Hypogamma globulinemia and subclass
deficiency or specific antibody deficiency
or another immunodeficiency
9 (19.1
Medical history
Serious acute bacterial infections
31 (68.1)
Chronic infections
44 (93.6)
Comorbid conditions
Stein et al. Postgrad Med. 2011; 123:186-93.
COPD
7 (14.9)
Type 1 diabetes
4 (8.5)
Type 2 diabetes
3 (6.4)
Patient Descriptions Cont.
Concomitant medication use in the larger study population
Parameter
Patients, n (%)
N=47
Brochodilators/inhaled corticosteroids
29 (61.7)
Proton pump inhibitors
21 (44.7)
Statins/antilipidemics
21 (44.7)
Nasal sprays
17 (36.2)
Antihistamines
16 (34.0)
Diuretics/antihypertensives
16 (34.0)
Antidepressants
11 (23.4)
Bone resorption inhibitors
10 (21.3)
Thyroid hormone
9 (19.1)
Stein et al. Postgrad Med. 2011; 123:186-93.
AC/AP Use: Patient Descriptions
• 33 patients total
– 26 from larger single-center in elderly, 7 from other centers
• Age
– Median: 70 years
– Range: 3−89 years
• AC/AP medications
– Included:
• Aspirin, warfarin, clopidogrel, and heparin
– Used for:
• Treatment and/or prophylaxis for thrombotic and vascular
diseases
– ie, pulmonary embolism, congenital heart disease, chronic atrial
fibrillation/flutter
Concomitant AC/AP Medications
• The most common
concomitant medication was
aspirin (18/33 patients, 55%)
• A large percentage of patients
were on warfarin (10/33
patients, 30%)
• Few patients used clopidogrel
alone or aspirin combined with
either clopidogrel or heparin
(5/33 patients, 12%)
Types of concomitant AC/AP
medications in patients treated with
SCIG
Patient SCIG Administration
Parameters
• SCIG was
administered
using a variety
of different
regimens
Mean duration of use,
months (range)
Mean total dose,
mg/kg/month
Number of sites per infusion
1
2-3
≥4
Method of SCIG Administration
Syringe Pump
Push
22.2 (5−49)
441
3
21
9
30
3
Site of infusion
Abdomen
Arm
Thigh
Multiple body areas
24
1
3
5
SCIG administration frequency
>1X/week
Weekly
Every 2 weeks
5
27
1
Results
• Local site reactions
– Mild, transient, and similar to those previously
described4
• Infusion-site bleeding/bruising: observed in only 1
patient
–
–
–
–
A 62-year-old white male
Immune thrombocytopenic purpura and SIDD
Receiving aspirin (81 mg/day)
SCIG dose of 710 mg/kg per month via syringe push,
20 mL in 1 site (abdomen), 4 times per week
– Reported mild bruising during the first month of SCIG
treatment
4. Jolles S, et al. Clin Immunol. 2011;141(1):90-120.
Case Study 1
• 21-year-old female
– 16% SCIG dose of 696 mg/kg per month
via syringe push
– Concomitant warfarin therapy (5 mg/d) for
treatment of prior pulmonary embolism
• First SCIG treatment
– Two 5 mL push injections (2 hours apart),
followed by two 10 mL injections (1 hour
apart)
– No photo available
Before
Week 4
Infusion
• Subsequent SCIG treatments
After
– One 20 mL push injection in one site over
15 minutes
– 3 times per week
• Patient outcomes
– No bruising, bleeding, or skin reactions at
the infusion site, despite increase in
general bruisability since starting warfarin
– After 8 months of well-tolerated SCIG,
restarted IVIG for personal reasons
Week 4
Infusion
Case Study 2
• 33-year-old female
– 16% SCIG dose of 750 mg/kg per month
via syringe push
– Concomitant warfarin therapy (alternating
9/10 mg/day) for chronic atrial flutter
• First SCIG treatment
• Subsequent SCIG treatments
• Patient outcomes
– No bruising, bleeding, or skin reactions at
the infusion site
After
Before
After
First SCIG
treatment
– Two 5 mL push injections (2 hours apart),
followed by two 10 mL injections (1 hour
apart)
– One 20 mL push injection in one site over
15 minutes
– 3 times per week
Before
Week 4
Infusion
Conclusions
•The concurrent use of AC/AP medications in this group of
patients with PIDD or SIDD aged 3-89 years did not
increase the occurrence of local site complications after
16% SCIG or 20% SCIG treatment.
•In patients with PIDD or SIDD and comorbid cardiovascular
or thrombotic disorders treated with AC/AP medications, the
use of 16% or 20% SCIG was well tolerated.