Pharmacy Times

IVIG and SCIG: A Look at Wellpartner Pharmacy

Author: Summer Kramer, PharmD, and Stacey Ness, PharmD

This home delivery pharmacy focuses on intravenous immune globulin programs to improve care and outcomes for patients.


Expensive therapy, clinical product variations, administration considerations, patient monitoring, and reimbursement challenges all add up to an ideal opportunity for a specialty pharmacy program focused on intravenous immune globulin (IVIG) and subcutaneous immune globulin (SCIG). Wellpartner Pharmacy, based out of Portland, Oregon, is a leading home delivery pharmacy dedicated to improving specialty pharmacy care and outcomes for patients. Dedicated patient care coordinators, reimbursement specialists, and after-hours access to nurses and pharmacists are just a few of the services available for patients receiving immune globulin (IG) therapy through Wellpartner.

Immune globulin therapy management can be complex, and there are various options for prescribers and patients to receive the required high level of pharmaceutical care. This review will outline some of the clinical and therapy management considerations for pharmacies providing an IG therapy program.

Overview of IG Therapy

By definition, intravenous and subcutaneous IG comprise a group of products with immunomodulating properties. Immune-mediated disorders that may warrant use of IVIG or SCIG can have various causative factors. The mechanisms by which IG may treat such factors can range from antibody replacement in immunodeficient states to macrophage Fc receptor blockade and inflammatory mediator suppression in some autoimmune disorders. 1,2 Immune globulin products are manufactured to contain greater than 95% IgG molecules with trace amounts of IgA and IgM.2 Because IG is produced from human donors (the FDA recommendation is between 15,000 and 60,000 US donors) and processed using a number of complicated manufacturing steps, its supply is finite with the potential for shortages and the need for allocations.3

Intravenous IG is approved by the FDA for 7 indications, and the subcutaneous formulation is currently approved for Primary Immunodeficiency. (See Table 1 for a list of FDA Approved Indications.) However, IVIG and SCIG are widely used off label for a variety of disorders encompassing diseases in neurology, hematology, immunology, nephrology, rheumatology, and dermatology. It is estimated that more than 150 off-label uses for IG have been reported in the literature.4 The American Academy of Allergy, Asthma, and Immunology (AAAAI) reviewed evidence for uses of IG in human disease, and those disease states for which IVIG was deemed to be “definitely beneficial” or “probably beneficial” are summarized in Table 2.3

The AAAAI Primary Immunodeficiency Committee recommends that for primary immunodeficiency the usual dose for replacement therapy with IVIG range from 0.4 to 0.6 g/kg administered by intravenous infusion every 3 to 4 weeks.3 Other indications, such as idiopathic thrombocytopenic purpura (ITP) and chronic inflammatory demyelinating polyneuropathy (CIDP), can have higher IVIG dose ranges, along the lines of 1 to 2 g/ kg given over 2 to 5 days.3,5,6 SCIG is administered as a weekly subcutaneous infusion using an external infusion pump over an average of 1 to 2 hours.

The literature states that due to the subcutaneous route of administration, there is a potential for SCIG to provide less systemic bioavailability due to possible incomplete absorption. Therefore, the FDA has recommended that SCIG dosing calculations accommodate for this possible decrease in bioavailability by the inclusion of a product-specific dose adjustment factor. 7 As stated in the product’s prescribing information, when converting a patient previously stable on IVIG, the initial SCIG dose should equal the previous IVIG dose (in grams) divided by the number of weeks between IVIG doses, then multiplied by the designated dose adjustment factor. (Please see individual product prescribing information for specific dosing and administration recommendations.)

Due to the complexity and route of administration, adverse reactions with both IVIG and SCIG are relatively common. Fortunately, the AAAAI has qualified most IVIG adverse reactions as mild, and reports that severe adverse reactions to IVIG occur only rarely.3 Such severe adverse reactions can include, but are not limited to, anaphylaxis, Stevens-Johnson syndrome, aseptic meningitis syndrome, acute renal failure, thrombotic events, and transfusion-related acute lung injury.

The aforementioned mild adverse reactions to IVIG can include headache, nausea, fatigue, chills, fever, urticaria, myalgias, and back or abdominal pain. Stopping or slowing the rate of infusion has been proposed to help alleviate some of the common IVIG adverse reactions. For those patients experiencing a consistent pattern of adverse reactions, premedication with diphenhydramine, acetaminophen, ibuprofen, hydrocortisone, and/or IV hydration have been used.3 Patients who are naive to IG therapy have a greater probability of experiencing an adverse reaction, and it is recommended that all first doses of IG be administered by a health care professional.

Compared with IVIG, the literature suggests that SCIG may produce a less severe set of possible adverse reactions.3,7 The most common SCIG adverse events are infusion site reactions such as swelling, erythema, itching, and mild pain at the site. Headache, fatigue, and nausea are additional adverse reactions that have also been frequently associated with SCIG therapy.5,6,8 While there is a reportedly lower incidence of severe systemic adverse events with the subcutaneous versus the intravenous formulation, there is an inherent risk of systemic reaction associated with the administration of any blood-derived product.7

IVIG Product Selection

When selecting an IVIG product, it is important to consider both patient risk factors and product considerations. Patient risk factors to consider include, but are not limited to, cardiac impairment and thromboembolic risk, for which volume load, sodium content, and osmolality are important product considerations; renal dysfunction and geriatric patients, which necessitate awareness of the product’s volume load, sugar content, sodium content, and osmolality; anti-IgA antibodies, for which it is important to choose a product with the lowest IgA content; and neonates/pediatric patients, for whom volume load, sodium content, osmolality, and pH are product factors to take into account.9

SCIG Therapy Considerations

Not all patients may be candidates for SCIG therapy, as successful selfadministration can require a significant level of technical training and comprehension. Further, some disease states, such as certain autoimmune conditions, require high doses of IG that are not able to be infused subcutaneously due to the increased volume load. However, the combination of a proposed decreased side effect profile, available training for self-administration, and quality of life improvements may make SCIG an attractive option for eligible patients. Possible clinical advantages of SCIG over IVIG may include more stable serum IgG levels due to smaller, more frequent dosing, and the possibility of reduced adverse reactions, specifically in those patients with an IgA deficiency.3

Each patient on SCIG therapy requires a unique set of supplies, which are determined by the patient’s dose, tolerability, and subcutaneous tissue depth. Multiple injection sites are used during the infusion in order to accommodate the volume associated with larger doses. SCIG is typically infused into various sites on the abdomen, upper arm, thigh, and/or the area of the outer hip, along with weekly site rotation. At 3 months’ post-initiation of SCIG, IgG serum levels should be monitored for proper dose adjustment if needed.6

A patient’s clinical response to therapy can also be monitored through consistent patient communication to track any new infections or hospitalizations that may have occurred. However, this level of follow-up can be challenging for both patients and prescribers. Additionally, reimbursement challenges may need to be overcome. Most private and federal insurance carriers cover SCIG under the patient’s medical benefit. Coverage and eligibility, lifetime maximums, deductible, and copays can be frequent obstacles to medication access.

SCIG Therapy Considerations 

Not all patients may be candidates for SCIG therapy, as successful selfadministration can require a significant level of technical training and comprehension. Further, some disease states, such as certain autoimmune conditions, require high doses of IG that are not able to be infused subcutaneously due to the increased volume load. However, the combination of a proposed decreased side effect profile, available training for self-administration, and quality of life improvements may make SCIG an attractive option for eligible patients. Possible clinical advantages of SCIG over IVIG may include more stable serum IgG levels due to smaller, more frequent dosing, and the possibility of reduced adverse reactions, specifically in those patients with an IgA deficiency.

Each patient on SCIG therapy requires a unique set of supplies, which are determined by the patient’s dose, tolerability, and subcutaneous tissue depth. Multiple injection sites are used during the infusion in order to accommodate the volume associated with larger doses. SCIG is typically infused into various sites on the abdomen, upper arm, thigh, and/or the area of the outer hip, along with weekly site rotation. At 3 months’ post-initiation of SCIG, IgG serum levels should be monitored for proper dose adjustment if needed.

A patient’s clinical response to therapy can also be monitored through consistent patient communication to track any new infections or hospitalizations that may have occurred. However, this level of follow-up can be challenging for both patients and prescribers. Additionally, reimbursement challenges may need to be overcome. Most private and federal insurance carriers cover SCIG under the patient’s medical benefit. Coverage and eligibility, lifetime maximums, deductible, and copays can be frequent obstacles to medication access.

A Look at Future IG Therapies

Since the first immune globulin product was approved in 1952, new formulations and indications have been in constant development. As of July 2011, 3 of the 5 pharmaceutical manufacturers that produce IVIG now have SCIG formulations approved by the FDA and at least 1 manufacturer is conducting clinical trials for a once-monthly SCIG formulation.10 In addition to the development of the subcutaneous route of administration, clinical trials have been conducted and more are in progress to study the safety and efficacy of immune globulin in various disease states outside of the primary immune deficiency disorders.

One such recent investigation centers on a possible immune component to the development of Alzheimer’s disease. The first Phase III trials for use in Alzheimer’s are set for completion in early 2013.11 Further pharmacy practice considerations revolve around product availability. As we have seen previously, the immune globulin market has had an inconsistent level of supply and demand. Without the ability to produce a synthetic immune globulin product, and an estimated 5.4 million people living with Alzheimer’s in the United States, an FDA-approved Alzheimer’s indication could have an impact on the overall market supply.12

Choosing an IG Therapy Program

Various program models exist for therapy management and care delivery for patients receiving IG therapy. However, the level of pharmaceutical care can vary between individual programs and providers. During assessment of possible program models, available services to look for include:

One such model for an IG therapy program is available through Wellpartner Specialty Rx Services, which provides comprehensive pharmaceutical care for patients and eases the challenges of IG therapies. Prior to dispensing, each IG referral is subjected to a full clinical review, which includes lab work and chart note assessment by a clinical pharmacist. The patient’s insurance benefits and eligibility are reviewed and the overall benefit status is communicated to the patient. Every patient is cared for by a support system of clinical pharmacists, reimbursement specialists, and a dedicated patient care coordinator.

Personalized programs are provided, including individualized supply and nursing needs. Depending on the level of patient experience with SCIG, 1 to 3 in-home nursing visits are scheduled for infusion training. Patient and/or caregiver education is a key component to therapy success and is a main objective during the in-home nursing visits. Infusion site reactions are usually mild to moderate, but for the subcutaneous route of administration, site reactions can be expected. Setting the appropriate expectations for those patients beginning SCIG therapy is essential for easing fears and increasing the probability of therapy adherence.

Even after proper SCIG training, patients are likely to have occasional questions or concerns during or between infusions. To provide consistent and reliable care, every patient on IG therapy has access to a trained infusion nurse or clinical pharmacist via a toll-free number 24 hours a day, 7 days a week. In addition, consistent lines of communication are maintained with the prescribing office during every stage of the referral process. Any delays in prescription processing are communicated, and if a referral is ineligible for service due to insurance denial or any other reason, all of the appropriate information is relayed to the prescriber’s office.

Monthly patient communication is performed by a patient care coordinator prior to each refill, and full clinical patient updates are sent to the prescriber for review at set intervals. The outcomes that are reported by patients during the monthly follow-up include the number and type of infections or hospitalizations that may have occurred and any new medications that have been introduced since the last report. This information is documented, reviewed by a clinical pharmacist and, if needed, communicated to the prescriber.

Collaborative Partners

In order to provide outstanding care to patients and providers and to recognize additional savings and services that positively impact the bottom line, Wellpartner has chosen to work with collaborative partners such as Specialty Pharmacy Nursing Network (SPNN) and Managed Health Care Associates, Inc (MHA), including MHA’s Specialty Pharmacy Solutions.

SPNN provides superior nationwide in-home nursing services for Wellpartner Specialty Rx Services. Available services include drug administration, first dosing, patient education, injection training, and after hours nursing phone support for patients receiving specialty therapies through Wellpartner Specialty Rx Services.

MHA is a leading healthcare services company that offers a wide spectrum of services and solutions to support the diverse and complex needs of alternate site and specialty pharmacy providers such as Wellpartner. MHA provides Wellpartner and other member pharmacies with a comprehensive portfolio of purchasing services for both pharmaceutical products and business solutions. MHA also offers contract management and business development opportunities to member pharmacies. In support of Wellpartner’s immunoglobulin business, MHA works with manufacturers and distributors to maintain a diverse contract portfolio of immune globulins and associated administration supplies and continually works to secure product access for members.

MHA’s Specialty Pharmacy Solutions program provides consistent tracking and analysis of trends in specialty pharmaceuticals to help Wellpartner anticipate what might be on the horizon and how to be in the best position to grow business and expand opportunities in the marketplace. MHA’s clinical services team also supports Wellpartner with clinical information to enhance disease state and specialty product knowledge as well as contract analytics and reporting to understand therapy specific and population metrics. SPT
 


References
 
1.      Dalakas MC. Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies. Neurology. 2002;59(12) (suppl 6):S13-S21.
2.      Scheinfeld NS. Intravenous immunoglobulin. Medscape Reference. http://emedicine.medscape.com/article/210367-overview#showall. Published August 2, 2011. Accessed August 17, 2011.
3.      Orange J, Hossny E, Weiler C, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol. 2006;117(4):S525-S553. http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS0091674906001783.pdf. Accessed August 17, 2011.
4.      Leong H, Stachnik J, Bonk ME, Matuszewski KA. Unlabeled uses of intravenous immune globulin. Am J Health Syst Pharm. 2008;65(19)1815-1824.
5.      Hizentra prescribing information. CSL Behring. www.hizentra.com/docs/hizentraPI.pdf. Published February 2011. Accessed August 17, 2011.
6.      Gamunex-C prescribing information. Talecris Biotherapeutics. www.gamunex-c.com/media/Gamunex_Prescribing_Info.pdf. Published 2010. Accessed August 17, 2011.
7.      Gammagard prescribing information. Baxter Healthcare Corporation. www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf?WT.svl=BiosciencePIs&site=www.gammagardliquid.com. Published 2011. Accessed August 17, 2011.
8.      Moore M, Quinn JM. Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency: advancements into the 21st century. Ann Allergy Asthma Immunol. 2008;101:114-121.
9.      Siegel J. IVIG medication safety: a stepwise guide to product selection and use. Pharmacy Practice News. www.pharmacypracticenews.com/download/IVIG_safety_ppn1210_WM.pdf. Published December 2010. Accessed August 18, 2011.
10.  Baxter Healthcare. Baxter presents data from interim analyses of Phase III clinical trial of HyQ at European Society for Immunodeficiencies Meeting. www.baxter.com/press_room/press_releases/2010/10_06_10_hyq.html. Published 2010. Accessed September 7, 2011.
11.  Baxter Healthcare. Baxter and New York-Presbyterian/Weill Cornell announce 18-month data from Phase II study of Gammagard in patients with Alzheimer’s disease. www.baxter.com/press_room/press_releases/2010/04_13_10_gammagard.html. Published 2010. Accessed August 16, 2011.
12.  Alzheimer’s Association. www.alz.org/index.asp. Accessed August 17, 2011.
 



Summer Kramer, PharmD, is the manager of specialty pharmacy operations at Wellpartner, Inc, a leading home delivery pharmacy and provider of specialty pharmacy services in Portland, Oregon. Dr. Kramer has experience in clinical program development, medication adherence management, contract pharmacy, 340B, and medication cost reduction strategies. Dr. Kramer received a bachelor of science degree from the University of Oregon and a doctor of pharmacy degree from the University of New Mexico.

 

Stacey Ness, PharmD, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence and persistency programs, and chronic disease cost optimization strategies. Dr. Ness has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is currently associate director of specialty services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.