Page 1181 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1146 ParT TEN Prevention and Therapy of Immunological Diseases

CLINICaL PEarLS 1 need to be instructed on the correct technique, made to apply it
Comparison of Routes of Administration of under close supervision, and educated about the recognition of
possible side effects. SCIG infusion is safer, better tolerated, and
Immunoglobulin Therapy in Patients With preferred by some patients. Several studies in Europe and Canada
Primary Immune Deficiency have shown that health care costs of SCIG therapy are lower
compared with IVIG. 14-16 It should be considered as an alternative,
Intravenous (IV) route
Advantages especially in those patients with systemic adverse reactions from
• Achieve rapid plasma levels IV administration. Recently, an alternative method for the admin-
• Can use this route in patients with bleeding disorders istration of Ig has been approved and has been referred to as
17,18
• 3–4 week intervals facilitated SC infusion. In this approach, human recombinant
hyaluronidase is used to enhance the volume of Ig (10% liquid
Disadvantages Ig) that can be infused in the SC space, allowing for monthly
• Need IV access doses of Ig to be administered in one or two sites. The hyaluronidase
• Interrupt patient’s schedule for 3–5-hour period depolymerizes the hyaluronan temporarily allowing the Ig greater
• Often needs to come to a hospital or infusion center access to the lymphatics of the SC space, facilitating the absorption
• System side effects may be more frequent in some patients
of Ig. This method of administration of 10% Ig has been shown
Subcutaneous (SC) route in pharmacokinetic studies to result in bioavailability of 93% of
Advantages the IVIG dose and thus does not require an upward adjustment
• IV access not needed for those patients with poor venous access factor in calculating the dose of Ig replacement. More details about
11,19,20
• Eliminate trough levels SC infusions can be found in several reviews.
• Achieve a stable serum level of immunoglobulin G (IgG)
• May eliminate 3rd–4th week fatigue prior to next infusion
(wear off) ADVERSE EVENTS ASSOCIATED WITH
• Less systemic adverse effects than IV route IVIG THERAPY
• More flexibility for patient’s (parent’s) schedule
• Distance from infusion center or hospital Rate-Related Adverse Events
• Young adults going to college
Typical rate-related adverse reactions with IVIG include tachy-
Disadvantages cardia, dyspnea, chest tightness, back pain, arthralgia, myalgia,
• Minor local reactions at the site of infusion hypertension or hypotension, headache, pruritus, rash, and
• Patient reliability low-grade fever. Mild to moderate reactions occur in 5–15% of
• Need for a pump infusions; severe reactions occur in <1% of patients. Of course,
in patients with autoimmune disorders, reaction rates are higher
with higher doses. Patients with more profound immunodeficiency
SCIG products are 10% or 20% formulations, the former being or patients with active infections also tend to have more severe
similar in composition to IVIG products. The calculated dose for reactions. Other factors that contribute to adverse reactions
SC administration is generally 100–150 mg/kg weekly. Depending include change of IVIG products, concomitant infections, higher
on the weight or body mass of the patient and the concentration concentrations or lyophilized products, and rapid infusion rates
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of the SCIG (i.e., 10% or 20%), infusions may have to be given (reviewed in the report by Stiehm ). The cause of the reactions
more frequently than every 7 days. Pharmacokinetics studies in is thought to be related to the anticomplementary activity of
clinical trials have suggested that upward adjustments in the dose IgG aggregates in the IVIG in which immune complexes form
of 37% of the IVIG dose may be needed to achieve comparable between infused antibodies and antigens of infectious agents in
bioavailability, defined as the area under the serum concentration the patient. The other possible mechanism is that the formation
13
curve (AUC). This adjustment in dosing between IVIG and SCIG of oligomeric or polymeric IgG complexes interacts with Fc
has not been mandated by European regulatory agencies, and in receptors and triggers the release of inflammatory mediators.
the United States some clinical immunologists select dosing based These rate-related reactions occur less frequently with the newer
on optimization of prevention of infections, as noted above for IVIG products that are liquid and isoosmolar. Headaches are
5,6
the IVIG dosing. Each subcutaneous infusion requires a small the most frequent symptom associated with IVIG infusions
portable syringe driver–type pump together with a 10–20-mL occurring in 5–20% of infusions and one-third of patients.
syringe and an infusion set with a specialized SC 25–27-gauge Slowing the infusion rate or discontinuing therapy until symptoms
needle. The length of the needle may have to be adjusted for the subside may diminish the reaction. Pretreatment with nonsteroidal
thickness of the subcutaneous tissue of each patient. Before infusion, antiinflammatory drugs (NSAIDs), acetaminophen (15 mg/kg/
the line needs to be checked to ensure that there is no blood dose), diphenhydramine (1 mg/kg/dose), and/or hydrocortisone
return. Infusions can be given weekly at multiple sites or more (6 mg/kg/dose, maximum 100 mg) 1 hour before the infusion
often (e.g., daily), if needed, to maintain adequate serum IgG may prevent adverse reactions. Oral hydration prior to the infusion
levels. The 20% SCIG product can be given every 2 weeks. Infusion is often helpful. Switching products may also lead to adverse
sites are usually on the abdominal wall and lateral thigh. In adults, events in 15–18% of patients and should be discouraged.
20–35 mL can be infused into a single site, depending on the
amount of subcutaneous tissue. A general guideline for infusion Central Nervous System–Related Adverse Events
rate is 15–35 mL/hr per site depending on the weight and sub- Aseptic meningitis has been reported as one of the complications
cutaneous tissue of the patient. The SCIG schedule should be of IVIG, especially with large doses and rapid infusions and in
21
started 1 week after the last dose of IVIG, or in a new patient the treatment of patients with autoimmune disease. Interestingly,
loaded with 4 or 6 doses of SCIG. Before home treatment, patients this rarely occurs in subjects with immunodeficiencies. Symptoms,