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Therapeutic agents in use for years may receive Food and Drug Administration approval for new indications, challenging infusion nurses to keep in mind differences in therapy for more than 1 disease state. For example, many infusion nurses are familiar with using rituximab in an oncology setting; however, because it has been approved relatively recently (February 2006) for treatment of rheumatoid arthritis (RA), infusion specialists must improve their understanding of how dosing and administration differ in the RA setting. This article focuses on the specific pathophysiology of the RA disease state and patient characteristics that may affect infusion therapy, illustrated by a case study.

Sara, a 42-year-old mother of 2, was diagnosed with rheumatoid arthritis (RA) 12 years ago. Her previous RA treatments have included nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, methotrexate (MTX), etanercept, and adalimumab. With several of these medicines, she experienced initial significant or partial response. With time, these agents either lost adequate efficacy or she developed adverse effects. Sara's rheumatologist had determined she was a good candidate for rituximab, a newer approved biologic therapy targeting B lymphocytes, which likely initiated and contributed to the progression of RA. Because his office was not set up to deliver infusion therapy, however, Sara had been sent to a hospital infusion suite for treatment. Although the infusion team had years of experience in administering biologic therapies, including rituximab, to oncology patients, this was the first patient they had seen with RA needing such treatment.

Cases such as Sara's are likely to be encountered more frequently by nurses with infusion therapy skills working in either hospital or office settings equipped with infusion suites. New infusion-based therapies for RA have extended the role of infusion nursing specialists experienced in administering these therapies, particularly those working in oncology settings. Thus, infusion nurses must understand the similarities and differences between medications for specific indications such as RA. Evolving research and new therapeutic options require that infusion specialists have current knowledge of these therapies for different patient populations.1

Infusion nursing specialists, in particular, need to understand the differences in the use of such drugs for RA compared with use in treating malignancies, including the following:

On physical examination, Sara had 20 tender and 15 swollen joints. Her laboratory tests revealed mild anemia, normal chemistry profile, and elevated acute-phase reactants (C-reactive protein, 15 mg/L; erythrocyte sedimentation rate [ESR], 32 mm/hour). Radiographic findings demonstrated periarticular erosions in both hands and both feet. Sara confided to the nurse her fear of becoming disabled. She stated, “At this rate, I'm afraid I won't be able to care for my two children.” Her husband traveled for business frequently, the family was newly transferred to this city, and she appeared alarmed and depressed about her lack of family and social support in the context of her disease progression.

In patients with RA, an inappropriate immune response against one's own tissue occurs, particularly involving cells of the joint (cartilage and bone) and joint lining (synovium) as well as, occasionally, cells of the blood vessels, nerve tissue, and lungs. This gradually leads to progressive joint destruction and disability; extra-articular disease manifestations, such as vasculitis and pulmonary fibrosis; and early mortality often related to inflammation-induced atherogenesis and cardiovascular disease.

A number of different cells are involved in the formation of inflamed infiltrated synovium. Activation of various cells of the immune system, such as antigen-presenting cells (macrophages, dendritic cells, and B cells), and effector cells, such as T lymphocytes, occurs as part of this process. This activation results in the secretion of molecules such as cytokines, including tumor necrosis factor (TNF) [alpha] and interleukins. These cytokines stimulate cellular receptors that promote inflammation and activate cells such as fibroblasts, chondrocytes, and osteoclasts, which can lead to cartilage and bone destruction.2

B cells, important constituents of the immune system, are the precursors of antibody-secreting cells (including rheumatoid factor); thus, they play an essential role in regulating immune responses.3 Although the extent of B-cell involvement in certain stages of RA is not entirely clear, they seem to serve as an important link to other immune cells and may direct the cellular components of the inflammatory process.3 B cells migrate into the synovium and are thought to initiate and perpetuate the progression of RA. The ability to deplete B cells using a monoclonal CD20 antibody, which targets the CD20 antigen expressed on the surface of peripheral B cells during maturation phases, has been associated with improved RA, providing evidence of the role of B cells in RA pathogenesis.4

In RA, excessive infiltration of the synovium by inflammatory immune cells, such as B cells, and increased vascularity and edema lead to thickening of the synovial lining.2 Clinically, this manifests as pain and stiffness in multiple joints, usually in the hands or feet, with synovitis and effusions causing the joints to swell.5,6 Over time, the inflamed synovium begins to grow irregularly, forming pannus tissue that invades and destroys cartilage and bone.6 Pain, joint erosion, and injury to the surrounding ligaments and tendons result in joint instability and deformity causing functional impairment.5,6 Muscles near inflamed joints often atrophy, causing weakness. Patients may hold joints in flexion to minimize the painful distension of joint capsules. Fatigue is a common problem, and low-grade fever, malaise, and other systemic symptoms may also occur, especially during an acute RA flare. Cytokines and other immune-response mediators are responsible for the development of systemic complications such as lung fibrosis, vasculitis, and neuropathy.5

Because her symptoms were increasing and she expressed anxiety about becoming disabled, Sara wanted to reevaluate her treatment and discuss new therapy options that might relieve her symptoms and help delay the progression of her disease. Her nurse and rheumatologist elicited the following therapeutic history: About 7 years ago, Sara stopped taking MTX and switched to TNF inhibitors because of her desire to become pregnant. She had tried various anti-TNF drugs. With her family complete, she resumed taking MTX in the past year in addition to the anti-TNF agent. Because of a waning response to these agents over the past several months, she had an increasing severity and duration of morning stiffness, painful joints, and fatigue that interfered with her busy life. She had been unable to escalate the dose of MTX beyond 15 mg because of nausea, malaise, and alopecia with higher doses. This treatment course—a dwindling or poor response over time—is typical of patients who have received several different drugs for RA. Sara now has clinical and radiographic evidence of disease progression. Based on this history, Sara's rheumatologist had determined that it was time to try rituximab therapy. Sara concurred but had many questions.

The goals for managing RA are to decrease pain and fatigue, prevent or control joint damage, limit the loss of function, and improve longevity. In the past, RA treatments were added on as disease severity worsened, but current expert consensus is that aggressive treatment early in the disease and tight control of disease manifestations are important to accomplish treatment goals.7

Table 1 illustrates the evolution of RA therapy. Traditional treatments of RA have included analgesics and NSAIDs to control pain and, to a minor extent, inflammation. Disease-modifying antirheumatic drugs (DMARDs) were developed to more fundamentally control the inflammation process by interfering with inflammatory cell function. Unlike NSAIDs, which do not influence structural damage, DMARDs slow the processes that result in joint destruction and anatomical deformities. Methotrexate, which interferes with the metabolism of inflammatory cells, is the most commonly used of these agents.11,12 A drawback to traditional oral DMARDs is that their mechanism of action is not specific and significant adverse effects may occur. They also require frequent blood monitoring and may be less effective at controlling disease progression in some patients.

TABLE 1 Advances in the Treatment of Rheumatoid Arthritis by Decade

During the 1990s, “biologic” treatments were developed, which limit the effects of specific inflammatory cells found in the synovium, such as macrophages, fibroblasts, dendritic cells, endothelial cells, T cells, and B cells, all of which influence various cytokines (inflammatory proteins). These agents are called “biologics” because they may closely resemble natural anti-inflammatory proteins or interact with specific molecules or receptors to mimic natural anti-inflammatory functions and are typically developed in mammalian cells. As proteins, they must be given parenterally either by subcutaneous or intramuscular injection or by infusion. These include the anti-TNF drugs, such as etanercept, infliximab, and adalimumab, and the interleukin 1 inhibitor anakinra.11 The introduction of anti-TNF agents dramatically improved treatment of RA by relieving signs and symptoms and inhibiting structural damage, even in patients who had not responded to DMARDs, including MTX.12 Despite the substantial effectiveness of TNF inhibitors, however, up to 40% of patients may not respond adequately to these agents and some patients lose their response over time.1 Like the older DMARDs, anti-TNF agents also increase the occurrence of serious infections, including opportunistic infections such as tuberculosis. When using these drugs, nurses must be vigilant in regularly asking patients about signs and symptoms related to infections.1 Other adverse effects, such as hepatic and hematologic reactions, may occur rarely.1

Patients who lose responsiveness to TNF inhibitors, never obtained a response, or have had adverse effects can potentially benefit from new therapies in development. Targeting B-cell activity became a reality when anti–B-cell monoclonal antibodies were developed in the early 1990s. The first B-cell depletion therapy used clinically was rituximab, a chimeric monoclonal antibody directed against the CD20 antigen expressed on the surface of most B-cell lymphoma cells and on normal peripheral B cells during maturation phases. After attaching to the cell surface, the antibody activates cell- and complement-mediated cytotoxic mechanisms, resulting in cell death.13 Success with rituximab in depleting B cells in malignancies led to trials in RA, where B cells also play an important role, likely driving the inflammatory process in synovium. Rituximab was approved by the US Food and Drug Administration in 2006 for use in combination with MTX so as to reduce signs and symptoms in adult patients with moderately to severely active RA, who have had an inadequate response to 1 or more TNF antagonist therapies.14 A new labeling update indicates that rituximab may slow structural damage as well.14

The use of rituximab in more than 1 million patients worldwide across all indications has provided a great deal of information about its safety profile. A recent evidence-based review concluded that, thus far, the rate of infections or other serious adverse events (AEs) in patients who initiated rituximab treatment after therapy with TNF inhibitors has not increased over the rate seen with other immune-moderating drugs used for RA.15 Although there have been no formal drug-interaction studies performed with rituximab, renal toxicity was seen in oncology clinical trials when rituximab was used in combination with cisplatin. In patients with RA, however, administration with MTX or cyclophosphamide did not alter the pharmacokinetics of rituximab.14

Rituximab is administered for non-Hodgkin's lymphoma (NHL), at 375 mg/m 2 intravenously (IV) once a week for 4 to 8 doses. For RA, it is given as 2 separate 1000-mg IV infusions, with 2 weeks between the doses. Table 2 summarizes the dosing regimen for patients who tolerate it well and for those who develop an infusion reaction.14

TABLE 2 Administration of Rituximab for Rheumatoid Arthritis

A major difference in administration is the fixed-dose regimen for RA versus body surface area (BSA)-based dosing for oncology patients. A study comparing rituximab exposure after fixed dosing in patients with RA reported that the distribution and clearance of rituximab after fixed and BSA-based dosing were similar.16 Fixed dosing resulted in only modest differences in drug exposure for subjects at extremes of BSA (<=10th and >=90th percentiles). Therefore, there does not appear to be a need for BSA-based dosing in patients with RA.16

Safety information for rituximab has been obtained from major clinical trials for oncology patients and for patients with RA. Adverse events can be categorized as infusion reactions and longer-term adverse effects, including those that occur with repeated administration over time. Table 3 summarizes key differences in rituximab for RA versus malignancy.

TABLE 3 Summary of Key Differences in Rituximab for Rheumatoid Arthritis Versus Oncology

Infusion-related reactions can occur during treatment with monoclonal antibodies, such as rituximab. Such reactions are thought to be caused by the marked release of cytokines, creating a flu-like syndrome of fever, chills, and rigors, with less common symptoms of hypotension, bronchospasm, pruritus, and rash. Less often, hypersensitivity reactions may occur, which can be distinguished from severe infusion reactions (cytokine release syndrome) by their appearance within minutes of starting the infusion.17

Infusion reactions to rituximab are mostly seen with the initial infusion and generally resolved upon discontinuation. The infusion can be stopped for 30 minutes to allow time for the reaction to be resolved, and then it can be started again at a slower rate. Subsequent infusions are associated with a reduction in the number of infusion reactions. This may be due to the decrease in circulating B cells, but the exact reason is unknown. Reactions can also be managed or prevented by premedicating with acetaminophen, hydrocortisone, and diphenhydramine.

Studies have shown that infusion reactions to rituximab tend to occur more in oncology settings versus RA settings. In a 24-month study of rituximab in indolent NHL, the most common AEs were grade 1 or 2 toxicities (chills or rigors, 26%; nausea, 21%; fever, 18%). Almost all AEs occurred during the first infusion. Infusion reactions appeared to be related to the tumor load, suggesting that such reactions might be less likely or less severe in patients with RA. Other grade 1 or 2 AEs related to infusions included flushing, hypotension, and headache.18

In general, studies have shown that infusion-related AEs in patients with RA were similar in type to those seen in oncology settings, but the overall incidence was noticeably lower and they were less severe. For example, The Dose-Ranging Assessment: International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER) study examined rituximab (500 mg or 1000 mg) plus MTX versus placebo.19 Most infusion-related AEs seen in this trial were associated with the first infusion (31%, 38%, and 18% in 500 mg, 1000 mg, and placebo groups, respectively).19 Furthermore, most infusion reactions were mild to moderate and easily managed.19 Stopping the infusion, treating the reaction, proceeding at a slower rate of infusion, and premedicating with IV glucocorticoids reduced the incidence of infusion reactions.

Another study of patients with RA, the Randomized Evaluation of Long-Term Efficacy of Rituximab (REFLEX) trial, compared rituximab plus MTX with placebo.20 Again, more infusion-related AEs occurred with the first infusion (23% vs 18%, rituximab vs placebo) compared with the second infusion (8% vs 11%, respectively) but were mild to moderate.20

In a recent open-label extension study of patients with RA who had previously completed 16 to 24 weeks of rituximab therapy, there was a decreasing incidence of infusion-associated AEs during repeated courses of rituximab.21 Within 24 hours of the first infusion, the proportion of patients with AEs decreased from 26% during the first course of therapy to 10% to 15% during courses 2 to 4.21 The investigators found that repeated courses of rituximab were not associated with additional safety events.

In the study on indolent lymphoma, overall, 29% patients reported fatigue, 6% had anemia, and 3% developed leukopenia—all grade 1 or 2 AEs. Only 2 patients developed grade 3 or 4 toxicity. No cumulative or additional toxicities were seen with maintenance courses.18

For patients with RA, 2-year follow-up safety data from an open-label study showed no differences in the occurrence of AEs, leading to withdrawal, serious AEs, or infections in the rituximab treatment groups compared with the placebo plus MTX group.22,23

In the DANCER study, serious AEs were reported in the rituximab group (7%) and in the placebo group (3%). Serious infections occurred in the placebo and rituximab 1000-mg groups at a rate of 3.2 versus 4.7/100 patient-years, respectively. No opportunistic infections occurred.19 In the REFLEX study, serious infections, defined as those requiring IV antibiotics, occurred at a rate of 5.2/100 patient-years for rituximab and 3.7/100 patient-years for placebo.20

A more recent safety analysis of the ongoing clinical program including 1053 patients exposed to rituximab (total exposure of 2438 patient-years; 120 patients with more than 3 years' exposure) showed overall tolerability was very good with no additional safety concerns or AEs beyond those seen in the original clinical trials.24

Patients should not take TNF inhibitors and rituximab at the same time. Although there are no clear guidelines for discontinuation of TNF inhibitors, in the DANCER and REFLEX studies, infliximab and adalimumab were discontinued for 8 weeks or more before randomization. Etanercept was discontinued for up to 4 weeks or more.19,20 Therefore, it is important to inquire about any DMARDs the patient has been taking and when they were discontinued. Although there are no clear guidelines on the length of time to wait between stopping DMARDs and starting rituximab, it seems reasonable to infuse rituximab when the next dose of the previously administered medication would have been delivered.

Sara arrived at the infusion center with reading material regarding the rituximab infusion and potential adverse effects, lunch, and knitting supplies. She had arranged for a ride home if necessary. Sara was premedicated with acetaminophen and diphenhydramine according to the center's protocol. She expressed an understanding of her treatment by stating that she had updated her diphtheria-tetanus booster and other needed immunizations before starting the therapy. Sara had been screened for hypertension and was not taking any antihypertensive agents. The nurse determined that Sara had no current illnesses. Sara asked about the common, mild reactions, such as flushing and itching, that she had read about, and the nurse clarified that reactions, in general, were more common during the first infusion but were generally mild compared with the oncology population.

Sara's first infusion of rituximab was complete in just over 4 hours with no AEs. The nurse scheduled a follow-up appointment in 2 weeks for the second infusion as well as an 8-week appointment with the rheumatologist to assess response to therapy. Sara was instructed to call beforehand if she experienced any illnesses or adverse effects related to therapy over the next few days.

Unsuccessful drug treatment is a reality and a major concern for many patients with RA, resulting in emotional as well as physical consequences. Patients experience anxiety and a high level of uncertainty and often have many questions as each new drug is introduced. Table 4 details potential questions and suggested answers. Living with a chronic and unpredictable illness such as RA requires social support and medical care.25 Nurses build a rapport with patients by listening, responding to concerns, and helping facilitate solutions.25 The nurse is often the first person to hear about an inadequate response to therapy and can act as an advocate for the patient in the reevaluation of therapy.1

TABLE 4 Information for Patients Starting on Rituximab

Patients must know the risks, benefits, and precautions accompanying new therapy, particularly because it will be administered by infusion. Issues regarding the infusion protocol and the management of AEs must be discussed to increase the comfort level with treatment. Vascular access, positioning, and comfort during the infusion, which may take several hours, are also considerations because joint pain, stiffness, and deformity may affect the ability to adhere to therapy. Patients also need education regarding postinfusion reactions, signs and symptoms of infection, and instructions on what to expect and when to notify the nurse or physician (Table 4).

Ongoing patient contact allows the infusion nurse to keep the patient well informed and to address concerns and questions. Because RA is a chronic disease with flares and remissions, a long-term treatment plan must be developed. Discussions should address disease prognosis and treatment, costs, adverse effects, expected time for response, individual risk factors, comorbidities, monitoring requirements of pharmacologic agents, and patient preferences. Expectations for treatment and potential barriers to carrying out the recommendations should also be discussed.7

Nurses need to be mindful that infection rates, in general, are higher in patients with RA than in the general population and should be alert for signs and symptoms of infection. Patients should be educated in this regard and learn how to prevent infection and identify signs and symptoms that warrant evaluation by a healthcare professional (Table 4).

When patients have concerns about the effects of RA on family life, these issues must be addressed. The combination of inflammation, pain, sleep disturbance, and poor nutrition causes severe fatigue, which is a major, debilitating problem for patients with RA. Loss of normal range of joint movement eventually results in loss of independence and mobility. Extra-articular manifestations, such as anemia, entrapment neuropathies, muscle wasting, osteoporosis, and vasculitis, may be as incapacitating as joint pain and stiffness.6

The variability of symptoms and chronicity of RA may lead to worries about future health status. The unpredictability of good and bad days makes it difficult to plan everyday events. Both men and women experience anxiety about their ability to maintain roles as parents, caretakers, and income providers. Depression affects up to 35% of patients with RA as they struggle to maintain autonomy and cope with the daily physical challenges of living with a chronic disabling disease. Physical limitations can curtail employment and social activities and may lead to social isolation. The family is also affected by all these issues.6 The infusion nurse may help identify problems stemming from the psychosocial aspects of disease while interacting with patients with RA during infusions. Patients often feel comfortable with nurses providing direct care and therefore allow themselves to bring up psychosocial issues they are not otherwise comfortable sharing with the physician or others. Awareness of these psychosocial issues allows the nurse to counsel patients and families and to provide information about local support groups or other services available for patients with RA.

The infusion nurse familiar with the use of rituximab in oncology should be aware that, overall, AEs in RA are usually mild to moderate and not difficult to manage. In general, AEs observed in patients with RA were similar to those in patients with NHL but occurred with less frequency.14 All patients should be provided with the rituximab patient medication guide and an opportunity to read it before each treatment session, with time to discuss any questions (Table 4).

Patients with RA are at increased risk of infections, in general, because of the autoimmune nature of the disease. Because depletion of B cells may also blunt immune response, the risk of infection is increased with rituximab therapy. Caution should be exercised in administering rituximab to patients with active infections, and patients' overall health should be assessed at each visit. In clinical studies of RA, the most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis. The only infections with an absolute increase over placebo of at least 1% were upper respiratory tract infections and rhinitis.14 Complete blood cell counts should be monitored periodically, typically every 2 to 3 months, because the patient is concomitantly taking MTX.14

Because rituximab affects B cells, an important question surrounds the efficacy of immunization with routine flu or pneumococcal vaccination following rituximab therapy. This question is undergoing study in patients with RA. Patients should be brought up-to-date with nonlive vaccinations prior to initiation of rituximab therapy and receive flu vaccinations annually, according to the Centers for Disease Control and Prevention's guidelines. Live virus vaccines are contraindicated with any biologic therapy, including rituximab, because response to primary and recall antigens may be lacking.14 If a patient with RA has significant cardiovascular risk factors, such as congestive heart failure or a history of arrhythmia, he or she should be monitored more carefully during infusion.14

In controlled trials of RA, acute infusion reactions, including fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, or bronchospasm (with or without hypotension or hypertension), were experienced by 27% of rituximab-treated patients after the first infusion, compared with 19% of placebo-treated patients. After the second infusion, incidences were 9% and 11%, respectively. Serious acute infusion reactions were experienced by less than 1% of patients in either treatment group. Acute infusion reactions required dose modification (stopping, slowing, or interrupting the infusion) in 10% and 2% of patients receiving rituximab or placebo, respectively, after the first course.14 Patients should be examined prior to administration, with each dosage increase, and throughout the infusion according to the infusion center protocol if any adverse effects occur.

Premedication with acetaminophen and an antihistamine before the first treatment is recommended to attenuate a potential infusion reaction. Methylprednisolone (100 mg) administered intravenously 30 minutes before the infusion may reduce the incidence and severity of an infusion reaction if one occurs.

Because transient hypotension may occur during rituximab infusions, if patients are being treated for hypertension, consideration could be given to withholding the antihypertensive agent for 12 hours before the first infusion as well as before subsequent rituximab infusions.14

Each infusion center should develop a standardized infusion protocol on the basis of detailed prescribing information from the manufacturer, patient history and comorbidities, and infusion center capabilities.

Some of the rarest, serious AEs are not typical anaphylactic reactions but are hematologic, usually occurring in patients with high B-cell counts (20,000 to 100,000/&b.mu;L) and in patients with risk factors for cardiopulmonary disease, which renders them more susceptible to bronchospasm or hypotension. Most patients with RA do not have risk factors associated with high B-cell counts, and most of these AEs are rare. Severe reactions occur most often with the first infusion. As B cells clear after the first infusion, the risk factors for AEs decline dramatically with further infusions.26

One of the major differences in using rituximab for oncology versus RA is the necessity for long-term therapy. Several ongoing clinical trials worldwide are investigating the efficacy and safety of rituximab maintenance therapy. Thus far, most patients have tolerated repeated courses of treatment without further toxicity.26 Results of clinical trials indicate that the most appropriate re-treatment interval is 6 to 12 months.27,28 To achieve an optimal response in the subsequent treatment course, the best timing of re-treatment appears to be as joint inflammation begins to return.

Because of its safety in oncology and RA, the use of rituximab in other autoimmune diseases is being explored, including idiopathic thrombocytopenia, IgM-mediated polyneuropathy, factor VIII deficiency, systemic lupus erythematosus (SLE), Sjögren syndrome, inflammatory myositis, pemphigus vulgaris, neuromyelitis optica, and antineutrophil cytoplasmic antibody-associated vasculitis. Open-label trials in various autoimmune diseases report varying degrees of efficacy.29 In trials of SLE,30 antineutrophil cytoplasmic antibody-associated vasculitis,31 and Sjögren syndrome,32 B cells were depleted rapidly, and treatment with rituximab resulted in improvement in various measures of disease activity. In 2 patients with SLE being treated off-label with rituximab along with other immunosuppressive therapy, fatal infection of the central nervous system, due to JC virus, also known as progressive multifocal leukoencephalopathy, occurred. Progressive multifocal leukoencephalopathy has been previously reported in patients with SLE as well as other in diseases associated with compromised immune systems. This has not occurred in RA patients treated with rituximab.

Sara began to feel more energetic and had less joint stiffness 1 month after therapy. She continued to improve, and at her rheumatology follow-up visit 4 months later, she had virtually no joint swelling or pain. Her laboratory markers for inflammation had returned to normal, and she expressed more hope for the future. She and her rheumatologist planned for re-treatment at the earliest sign of disease return (fatigue, morning stiffness, swollen or tender joints), with the understanding that most RA patients undergo re-treatment at 6 to 9 months on average.

As with any other therapy, RA symptoms may recur after treatment with rituximab. Patients need to be educated about when to contact the rheumatologist so the next course of therapy can be administered in a timely manner. Because data collection on patients receiving this treatment is ongoing, nurses need to keep an eye on the literature regarding subsequent treatment.

Infusion nurses with experience of administering rituximab in oncology can apply these skills to patients with RA but should be aware of key differences (Tables 2 and 3). Administration is based on a fixed-dose regimen in RA rather than on BSA. Infusion reactions in RA occur less frequently, decline in frequency during subsequent courses, and are generally mild to moderate. Clinical trials on RA have shown that AEs tend to be less frequent and less severe than in oncology trials. Rare life-threatening reactions, such as tumor lysis syndrome, are not expected in RA. Because RA patients are more likely to require long-term therapy, research on maintenance therapy with rituximab for RA is ongoing.

The variety of therapeutic options for RA has increased patients' opportunities to choose a treatment regimen specific to individual needs and lifestyles. The infusion nurse can assist the patient in making informed decisions by providing information about different therapies, including benefits and potential adverse effects. Infusion nurses must be well versed in rituximab infusion, and informing the patient about what to expect may increase treatment adherence. To answer questions and address concerns, the infusion nurse must be well informed about the mechanisms of action of new therapies and how they are administered safely in patients with RA. By screening patients before drug administration, monitoring for adverse effects, and continually evaluating response to therapy, infusion nurses can assist patients in managing their disease. They can also be an advocate for patients, when changes in drug therapy might be indicated.1

The authors thank Patricia A. Nixon, PA, and Gail M. Pfeifer, MA, RN, for their assistance in the preparation of this manuscript.

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