Adapted from a presentation at the SLE Workshop at Hospital for Special Surgery
In 1994, Stephen A. Paget, MD, FACP, FACR, then Chief of Medicine at Hospital for Special Surgery, created an infusion therapy unit for people with rheumatologic disorders. This HSS infusion therapy unit was the first in the country dedicated specifically to the care of people with rheumatology-related autoimmune mediated disorders and opened long before intravenous medications for lupus and arthritis were developed.
A few years later, the field exploded with a variety of medications for arthritis, lupus and all rheumatologic illnesses. In 1999, the first intravenous biologic medication for people with rheumatoid arthritis was approved. In the ensuing years the “off label” use of biologic agents increased.
Through the years, a growing number of medications for people with autoimmune diseases were developed, including those for people with lupus.
Infusion therapy refers to all medications that are administered intravenously, that is, through the vein or by IV. These medications are generally administered in an infusion unit. Whenever an IV medication is prescribed, patients should discuss with their doctor the timing of treatment and how to prepare for administration. This is particularly important because at HSS, many of the medications given in the infusion unit suppress the immune system.
Precautions must be taken for all infusion medications. The patient must be in good health with no active infections. Infusion medications should not be administered prior to, or directly after, surgery including oral/dental surgery. Any procedures such as a colonoscopy that may lead to a biopsy also warrants a discussion with your MD and possible postponement of infusion. Patients should reschedule their infusion if they are not feeling well and should communicate this to their healthcare provider prior to the appointment.
The following the key types of infusions treatments for lupus:
Steroid methylprednisolone (brand name Solu-Medrol) is the cornerstone of treatment and can be given both orally and intravenously, sometimes at the same time. IV administration is started in order to maintain an oral dose or to decrease an oral dose. A patient may be currently tapering off of their oral steroids and experience a small flare. In this case the physician would administer a “pulse steroid” which is a few days of a high dose of intravenous steroid in order to maintain the oral dose or even taper off the oral dose. This is done because the side effects of intravenous steroids are often more temporary than those of oral steroids.
The typical dosage at HSS (which may differ at other institutions) is 250mg to 1000mg (the latter number is equivalent to one gram) per day. Often patients will receive one gram per day for up to three days. Infusion time is about one to two hours. This medication is often used in conjunction with other medications.
One of the possible side effects of methylprednisolone is an increase in blood pressure. Patients should be sure to keep taking their blood pressure medication when receiving methylprednisolone by infusion. Another side effect is a temporary increase in blood sugar. Unfortunately, steroids can also induce cravings for sugar and salt. Patients with diabetes must be especially vigilant about their sugar intake and all patients should be educated to watch their salt intake. In addition, steroids can cause weight gain and bloating. Intravenous steroids can cause patients to retain salt and fluid, leading to a gain of three to five pounds during a three- to five-day course of treatment. The increase in salt will also increase joint pain in patients for whom this is already an issue.
Patients may experience “steroidal flush” of the skin due to vasodilation (dilation of the blood vessels). A steroid rash that looks like a series of tiny pinpricks may also occur around the face and back. These reactions are not regarded as a reason to stop steroid therapy, but patients should report their occurrence to their doctor. Headaches are the most common side effect of steroid therapy. Ms. Leff suggests that patients take the same over-the-counter medication they usually take for headaches before beginning steroid treatment. Other side effects of steroids are: mood swings and irritability especially when given a large dose; gastrointestinal problems such as nausea, bloating and diarrhea; insomnia and hair loss. Ms. Leff recommends eating a bland diet during administration of steroids and, when possible, scheduling infusions early in the day to lessen interruptions in sleep patterns.
For the most part, the side effects of intravenous steroids will go away within a week after administration. However, some long-term side effects may be seen with both oral and intravenous steroid use. These side effects include cataracts, steroid-induced diabetes, and bone problems such as osteoporosis and avascular necrosis (AVN), a condition in which the bone dies due to inadequate blood supply. Patients on long-term steroid therapy should have eye exams and bone density tests. Individuals with steroid-induced diabetes will often go into remission (a temporary recovery or lessening of symptoms) if they watch their diet after ending steroid therapy.
Cyclophosphamide (brand name Cytoxan) is a cytotoxic (toxic to living cells) agent that suppresses both red and white blood cells in the bone marrow. This medication is typically used for patients with organ disease. It is used most frequently for kidney disease and sometimes for lung and heart disease. This medication is not used for generalized lupus flares or for skin issues.
The typical dosage is 500mg to 1000 mg. Dosage is based on the patient’s body surface area, which is calculated using height and “dry” weight (the patient’s weight without the excess fluid often seen in kidney disease). Cyclophosphamide takes an hour to infuse, but the entire treatment is a longer process and takes five to six hours. At HSS patients are given fluid for two hours prior to receiving the medication and for two hours afterwards. Patients also receive a medication called mesna (Mesnex) to avoid cystitis, a severe irritation of the bladder that can occur with cyclophosphamide therapy. Patients undergo cyclophosphamide therapy every three to four weeks, with the frequency of administration determined by the physician and based on the severity of the patient’s illness.
Patients will need to have lab work done before receiving cyclophosphamide to assess their white blood cell count. This is due to cyclophosphamide’s suppression of both white and red blood cells. White blood cells protect against infection and physicians want to be sure that the patient’s white blood cell count does not go so low that he or she is at an increased risk of being susceptible to infection.
Because cyclophosphamide may cause nausea and vomiting, medications such as ondansetron (Zofran) and granistron (Kytril) may be administered to control these side effects. To address complaints of “not feeling well” or not having an appetite, Ms. Leff recommends following a bland diet while receiving cyclophosphamide. Patients may also experience delayed nausea two days after receiving an infusion. If this occurs, patients should notify their doctor and who may change their protocol by adding steroids, along with their other anti-nausea medications. Patients will often experience fatigue two days after their infusion leading many to schedule their infusions on a Thursday or Friday in order to give themselves the weekend to recuperate.
Another potential side effect of cyclophosphamide is hemorrhagic cystitis, a very irritating urinary infection characterized by blood in the urine. During cyclophosphamide therapy it is very important to drink large quantities of fluids to help protect against hemorrhagic cystitis. Patients should also make sure to mix the type of fluids they drink since drinking only water may result in a reduction of electrolytes. If a patient develops hemorrhagic cystitis, he or she will be taken off of cyclophosphamide.
There have been cases of malignancies caused by cyclophosphamide. Patients should always discuss cyclophosphamide therapy with their doctor to make sure that the benefits outweigh the risks. Ms. Leff also reminded patients to always be honest with their physician about adherence to their medication regime since physicians will only put a patient on cyclophosphamide if they feel that the oral medications are not working. In some cases, patients may not need a new or different medication; it may simply be an adherence issue that is responsible for a lack of response.
Eight to ten days after receiving a cyclophosphamide infusion for the first time, patients undergo a test to check their white blood cell count. At this point the count will hit the lowest level (also called the nadir) and physicians will want to make sure that it is not too low. cyclophosphamide is initially administered at a low dose and slowly increased based on the cell counts during the nadir phase. It is not uncommon for patients to have neutropenia (very low white blood count). Because white blood cells play a key role in the body’s immune response, it is important to monitor for infection. Patients who feel sick should call their doctor immediately so that they can be prescribed antibiotics if needed. In addition, patients should be more proactive when they are receiving cyclophosphamide than at other times and should not wait until they have a high fever to get medical assistance.
Rituximab (Rituxan) and biosimilar rituximab-abbs (Truxima) are biologic agents that deplete B cells (cells that produce antibodies) by binding to CD20+, a protein on the surface of certain B cells. The medication has been approved for lymphoma and rheumatoid arthritis. It is used “off label” (without FDA approval) for lupus because B cells play a very important role in the disease. This medication has mixed results in lupus, but works for some patients.
Rituximab dosage is one gram (1000mg) to start and at two weeks, then every 16 to 20 weeks. All patients receive pre-medications of diphenhydramine (Benadryl), acetaminophen (Tylenol) and a small dose of steroids before the infusion to prevent an infusion reaction (see below). Rituximab infusion can take up to six hours. The first infusion lasts five hours and is titrated starting at a low rate with an increase every half hour. If a patient reacts well to the first infusion, the second infusion will begin at a higher rate and the infusion will take four hours. While on Rituxan, patients should not receive live vaccines.
Patients may experience mild to severe infusion reactions such as chills, itching, high temperature, hives, difficulty breathing, and chest pain. If patients experience any symptoms during the infusion, it is very important to let the nurse know immediately. In such situations, the medication will be stopped, fluids will be administered and the reaction will be cleared before resuming the infusion at a lower dosage. If a patient has a very strong reaction they may need to discontinue the infusion. Patients may not feel an improvement for the first four to six weeks after their second infusion of rituximab, but this does not mean that the medication is not going to work. After their infusion, patients may experience fatigue, increased joint pain, and headaches; they are also at increased risk of infections. Patients taking rituximab are especially prone to sinus infections.
The most serious potential side effect of rituximab is progressive multifocal leukoencephalopathy (PML), an infection of the brain, which can manifest in a number of ways including trouble with gait, speech and memory. If a patient develops the condition, it will be very obvious that he or she is not well. PML is caused by a virus that has been present since childhood, but has previously been dormant. Those who are severely immunosuppressed can get PML, which can be fatal.
Belimumab (brand name Benlysta) is the first biologic agent (approved in March 2011) specifically for the treatment of lupus. Belimumab acts by blocking B lymphocyte stimulator – a protein found in very high levels in lupus patients – that allows B cells to live longer. B cells cause much of the autoantibody activity seen in lupus. This medication is indicated for autoantibody-positive, active lupus patients and is not for people who have inactive lupus. Belimumab is not approved for people with organ disease. Patients with severe fatigue and joint pain are doing very well on belimumab.
The dosage is 10mg per kg. Patients are given a loading dose and will have medication three times every two weeks for three doses and then once every four weeks afterwards. Benlysta takes one hour to administer.
The side effects for Benlysta include:
Intravenous immune globulin (abbreviated IVIg) is immune globulin IgG derived from human plasma. How IgG works is not clearly understood. This infusion is used for people who have lupus with myositis, complaints of body aches and pains, and muscle weakness.
IVIg dosage is based on the patient’s weight. The length of infusion varies significantly (anywhere from 2 to 10 hours) and is based on the dosage (total grams) and rate, as well as how the patient reacts to the infusion. The infusion rate begins slowly and is titrated (measured and adjusted) on an individual basis.
Patients may experience infusion-related reactions to IVIg including: headaches, chills, fevers, shortness of breath, and chest pain. If any of these reactions occur, the rate of the infusion is lowered to lessen the effects. Other complaints or side effects are gastrointestinal upset and nausea. Patients may experience aseptic meningitis syndrome, which is a non-infectious inflammation of the meninges (membranes that line the brain and spinal cord) that causes headaches and a stiff neck, but this will go away with increasing fluid intake, rest and Tylenol. If a patient experiences aseptic meningitis syndrome, the infusion will be administered at a slower rate at the next appointment.
Anifrolumab-fnia (brand name Saphnelo) is newest intravenous medication for Lupus, approved by the FDA in 2021.
Anifrolumab is a fully human monoclonal antibody. The medication works by binding to certain cytokines, Type I interferons. Type I interferons are cytokines involved in the inflammatory process. A large percent of adults with lupus have an increase of type I interferon. Blocking these type of interferons can help to lessen disease activity. The medication is used for people with moderate to severe lupus.
The dosage is 300mg given intravenously over 30 minutes every four weeks. People being treated with anifrolumab-fnia (Saphnelo) should not receive live vaccines while on this treatment.
Possible known side effects of Saphnelo include:
Learn more information about the SLE Workshop at HSS, a free support and education group held monthly for people with lupus and their families and friends.
Linda Leff, MPA, RN NE-BC
Patient Care Director, Infusion Therapy
Hospital for Special Surgery