By Peggy Clinton, BSN, Eric Hill, Wanda Rogers, RPH
As many of you know, Pemphigus is an immune-mediated blistering skin disease involving the IgG autoantibodies which bind to the cell wall of the epidermis. The specific pathway of the blistering process is not well documented. The disease may be a primary diagnosis for the patient, induced as a result of certain medications or, in the case of paraneoplastic pemphigus, may be related to another disease process, becoming a secondary diagnosis for the patient.
The human immune system produces IgG and other antibodies, which normally attack viruses and bacteria, to prevent infections. In a person with Pemphigus, the antibodies mistakenly view the person’s own skin as a foreign body, causing lesions of varying size and location. These lesions will not heal and become at risk for infection.
Over the years Pemphigus has been treated with a variety of medications, including corticosteroids, and immunosuppressive or anti-inflammatory agents. Treatments with immunosuppressive drugs include azathioprine, cyclophosphamide, cyclosporine, and methotrexate. Anti-inflammatory drugs include gold, dapsone, tetracycline and nicotinamide. No single therapy, other than steroids, has been consistently reported beneficial at this time.
The goal of these medications is to reduce production of the pathogenic antibodies, but prolonged immunosuppression may be associated with severe side effects, including an enhanced susceptibility to opportunistic infections. As a result there is a need for the development of an alternative treatment for Pemphigus.
There are other medications on the market that are approved for other immunologically suppressed patients that are beginning to be considered for Pemphigus.
IVIG acts rapidly and does not suppress the immune system.
Although the FDA has not approved IVIG for use in treating Pemphigus, some physicians are prescribing IVIG for that use. Prescribing a drug which is not approved for a particular condition is called an “off label use.” Because of the relative rarity of Pemphigus, it is unlikely that any U.S. drug manufacturer will make the research investment necessary to obtain an “indication” or approval from the FDA. It should be noted that it has been estimated that over half of all IVIG use in the U.S. is for off-label uses (citation, which source?).
What is IVIG Therapy?
IVIG is Intravenous Immune Globulin therapy prescribed by a doctor to treat a disease or condition. The Food and Drug Administration (FDA) has approved the treatment of many diseases or conditions with IVIG.
IVIG therapy is prepared from human plasma and has at least ninety percent IgG with small amounts of IgA and IgM present in the final product. Manufacturers make IVIG using several different methods during the manufacturing process to help provide a safe product. The IVIG product is pooled from as many as 2,000-10,000 donors. Donors are screened for HIV and Hepatitis viruses (B and C) so that patients can be assured that the risk of getting these diseases is reduced. Most products on the market worldwide also go through at least one viral inactivation step in order to kill any remaining active viruses in the unlikely event one is present after the manufacturing process.
How it is Given?
Immune globulin (IVIG) may be administered intramuscularly, intravenously or subcutaneously. The intramuscular route may cause local irritation, soreness or pain at the site. As a result of these painful injections, many patients do not continue therapy.
IVIG is usually given intravenously (through a vein). A nurse usually places a catheter in the vein and the patient removes it when the therapy is complete. When therapy is ordered for a long period, many doctors suggest the patient have a permanent catheter placed to prevent having to be “stuck” with a needle for repeat treatments.
Immune globulin is also given subcutaneously (needle is placed just under the skin). This method of administration is used less frequently and can cause discomfort at the site. Some immune globulin prescriptions may be ordered at slower rates continuously for several days. The subcutaneous method is better suited for these slower rates to maintain the IG level. Most patients who receive IVIG for Pemphigus receive such large doses that subcutaneous administration is not practical.
Because of the large doses that most physicians prescribe for Pemphigus patients, the IVIG usually is given intravenously over several hours, typically for several days in a row. This is called a “course” of therapy. A typical course of therapy may require 2-6 hour infusions for 4-5 days in a row. Keep in mind that each patient is different and administration times vary from patient to patient.
What Side Effects are Reported?
Some patients receiving IVIG therapy can experience serious side effects. These do not happen often, but if they do, they should be reported to the patient’s pharmacist and to the ordering doctor right away. These symptoms should be considered an emergency: faintness, confusion, itching, headache, fever, chest, hip or back pain, and kidney problems.
More serious symptoms include high blood pressure, fast heart rate, swelling of the face or tongue and trouble breathing. It should be noted that the occurrence of severe symptoms and true adverse drug reactions are rare. As a matter of reference, Coram Healthcare administered over 17,000 courses of IVIG to more than 2,400 patients at home in 2000 with very few reports of adverse drug reactions.
The following side effects are not an emergency but should be reported to the patient’s pharmacist or doctor. These should go away if the rate of infusion is slowed. Side effects usually indicate that the medication is being given too quickly (if intravenous): nausea, stomach pain, flushing, and headache.
If a patient experiences side effects, the next dose may be started after the patient receives pre-medication.
The pre-medication does not prevent the side effects from occurring, but will generally minimize the symptoms so the patient is more comfortable during the treatment. Pre-medications may include acetaminophen, Benadryl or Hydrocortisone. Taken 15-30 minutes before the dose is due, these medications may help decrease the side effects.
If a patient experiences side effects, the doctor may decide to start therapy again at a later date with a different brand of IVIG. Patients may react differently to the various products even though there are a lot of similarities in each product. If a patient experiences serious side effects, the next dose should be infused at the hospital or doctor’s office to closely monitor the patient.
Fever, muscle aches or tiredness may occur hours or days after a dose is infused. These symptoms are generally very mild and may be treated with comfort measures such as acetaminophen, aspirin or non-steroidal anti-inflammatory medicines as recommended by the physician. These symptoms will not prevent the patient from receiving additional doses in the future.
Where Can Patients Receive IVIG?
IVIG can be given in the hospital (usually the first 1-2 doses, depending on the patient’s response), doctor’s office, ambulatory infusion center or in the patient’s home if there are no complicating medical problems. The doctor and discharge planner (if admitted at the time of diagnosis) will work with the patient to determine the best location to receive the therapy. Many patients prefer to receive the IVIG in their own home due to comfort and convenience to their lifestyle, or childcare responsibilities. Because patients are ambulatory (able to move about while receiving the infusion) it is even possible to receive IVIG while at work, provided there is a safe environment and good environmental assessment is done by a nurse prior to choosing this as a site of care.
What Can I Expect from Home Therapy?
Successful IVIG treatment at home includes:
- a patient willing to be a part of the treatment (and having an adult partner or nurse to help give the IVIG) infusing the IVIG on schedule, as the doctor has ordered;
- the ability and willingness of the patient to be seen frequently by a physician to check their progress according to the doctor, pharmacist or nurse’s instructions and to report important facts back to the health care team;
- a physician readily available to monitor the procedure and treat adverse events.
The hardest part of the therapy for most people is having their IV catheter inserted. If the doctor has not already arranged for a central line (catheter in the chest), a nurse can insert a small, temporary IV catheter at the start of the infusion. Once the IV is in place, the patient or carepartner will prepare the infusion as instructed by the nurse. Most home infusion companies provide instruction sheets as a guide.
IVIG is usually prescribed every two weeks to once-a-month administration so the catheter will only stay in as long as the therapy is infusing. The patient or carepartner will pull the catheter out, as shown by the nurse. If the therapy is to infuse for more than one day, the catheter may stay in place until the doses are completed. The nurse will also describe signs to watch that a catheter has slipped out of the vein – or any other problems that would mean a new catheter is needed.
Doctors rely on the patient to let them know how effective the therapy is between office visits. It is important to write down how the patient feels before, during and after the infusion. How a patient feels or responds may alter the frequency of the infusions (either moving them closer together, or moving them slightly further apart.)
How Much IVIG Will I Need?
The doctor will order the dose and amount of IVIG to give, based on the patient’s body weight. It is very important for patients to have their weight taken prior to the treatment. Any significant weight increase or decrease of at least 10% of the patient’s body weight may affect their dose.
Patients with Pemphigus usually receive 0.4 g/kg (grams of IVIG per kilogram* of body weight) per day for 5 days. Other investigators have reported good effects with 1-2 g/kg per day over 2-5 days. As an example, a 150-lb person would receive a 136-gram course divided equally over 5 days, or about 27 grams per day. (*One kilogram is equal to 2.2 lbs.)
Will insurance pay for IVIG?
There is no easy answer to this question. Because the use of IVIG is relatively new in the treatment of Pemphigus, each insurance company typically handles authorizing payment differently. The use of IVIG in other autoimmune disorders has become more commonplace. Some commercial and government insurers have recognized it as a standard of care for Pemphigus and have provided coverage for this therapy for some patients. Some insurance companies recognize the potential benefits of the appropriate use of IVIG and may provide coverage for the drug.
It is very important that the patient confirms that their insurer has “authorized” the use of IVIG before being treated, due to the high cost of the therapy. The provider of care should work with the patient to not only gain authorization, but to ensure that he or she is billed correctly. Coram, for example, has reimbursement specialists who work with local and national insurance companies and HMOs to obtain approval. Coram will work with the physician to resolve appeals and denials of authorization.
Interestingly, Medicare does not currently provide reimbursement coverage for the infusion of IVIG in the home. Medicare will however, cover the administration of IVIG in an outpatient clinic, a doctor’s office, or in a hospital.
Each state Medicaid plan handles the payment for IVIG differently. Patient’s should check with their doctor or IVIG provider to determine if their state Medicaid plan will cover IVIG therapy.
How much does it cost?
IVIG is a very expensive therapy. The cost of the therapy is high for several reasons; the availability and cost of collecting the plasma used to make IVIG: extremely tight regulatory oversight from the FDA; complex viral testing; expensive manufacturing process; and high worldwide demand for the product. While not an exact estimate, a good “rule of thumb” is that IVIG therapy, inclusive of all services, will cost about $90 per gram. Keep in mind that there are many things that can cause the cost to vary, including; your insurance company, the dose, the product selected, the location of infusion, and the duration of the infusion. In the above example in which a 150-lb person receives a 136-gram course of IVIG the total cost paid by the insurance company may be $12,240 (assuming $90 per gram), plus the cost of administering and supervising the treatment.
While the cost of the IVIG infusion may be high, the therapy is generally infrequent (usually not daily); patients are involved in their care (decreasing nursing costs) and have the benefit of improved health. The patient, physician, insurance case manager and the infusion provider should work together as a team to determine the best care for the patient.
IVIG treatment is still experimental. It seems to be effective, but the actual degree and length of effectiveness and the optimum dosages and intervals are still being determined. Adequate and frequent medical supervison of treatment is necessary.
Peggy Clinton, BSN works for Coram Healthcare as the Clinical Operations specialist for Blood Products, Wanda Rogers, RPH is an Area Pharmacy Director for Coram Healthcare, and Eric Hill is the Vice President in charge of Blood Products for Coram Healthcare.
These materials are designed for educational purposes only and are not intended to substitute for medical advice. Do not use this information to diagnose or treat a health problem or disease without consulting with a qualified physician. You should always consult your physician before starting any course of supplementation or treatment. Never disregard medical advice or delay in seeking it because of something you have read on these materials.
©2002 Coram, Inc. All Rights Reserved.
1. Immunoglobulin Shows Promise in Steroid-Resistant Pemphigus By: Erik L. Goldman, New York Bureau [Skin & Allergy News 29(1): 26, 1998. © 1998 International Medical News Group.]
2. Lawrence Chan, M.D., Director, Assistant Professor, Department of Dermatology, Section of Immunodermatology, Northwestern University.
3. Results of survey on drugs used to treat Pemphigus. By Rebecca Berman, Janet Segall and Jean-Claude Bystryn, M.D. from The National Pemphigus Foundation and The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY February 17, 1999.
4. Dermatology Times (Oct, 1998). New Drugs Offer Hope for Pemphigus Patients. Andrew Bowser.