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 ImmunodeficienciesOctober 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.

• 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

Introduction

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– 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

Rationale and Objective

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

COPD 7 (14.9)

Type 1 diabetes 4 (8.5)

Type 2 diabetes 3 (6.4)Stein et al. Postgrad Med. 2011; 123:186-93.

Patient Descriptions Cont.

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)

Concomitant medication use in the larger study population

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) 22.2 (5−49)

Mean total dose, mg/kg/month 441

Number of sites per infusion 12-3≥4

3219

Method of SCIG AdministrationSyringe PumpPush

303

Site of infusionAbdomenArmThighMultiple body areas

24135

SCIG administration frequency>1X/weekWeeklyEvery 2 weeks

5271

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

treatment4. 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• Subsequent SCIG treatments

– 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

Week 4 Infusion

Before

After

• 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

– Two 5 mL push injections (2 hours apart), followed by two 10 mL injections (1 hour apart)

• Subsequent SCIG treatments– 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

Before After

First SCIG treatment

Before After

Case Study 2

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.