Conversations in Rheumatoid Arthritis (RA) Therapy: Choosing Between Subcutaneous Injections and Infusion Therapy © Thinkstock by Getty Images
As we consider how to approach our decision-making in selecting a biologic disease-modifying anti-rheumatic drug, specifically the tumor necrosis factor antagonists (anti-TNFs), we are confronted with many questions: • Which modality will work best for each patient, subcutaneous self-injection or infusion? • What are our patients’ fears and concerns, including efficacy and safety issues, for each therapy? • How do their individual insurance benefits and financial obligations influence their choices? • How can we as clinicians better answer these questions and outline the pros and cons of each modality and the impact on their decision? It is crucial to encourage shared decision-making between patient and physician. We need to initiate the conversation with our patients to educate them so that they may be able to make informed decisions, and we need to encourage them to feel comfortable enough to express their feelings and ask questions. Additionally, we need to have further discussions when we consider switching agents, whether it is due to incomplete response, adverse events, insurance issues, or patient preference.
Ellen M. Field, MD, FACR FACULTY REVIEWER Ellen M. Field, MD, FACR Rheumatologist Lehigh Valley, Pennsylvania
Dr. Field is a paid consultant for Janssen Biotech, Inc.
hen it comes time for your patient with rheumatoid arthritis (RA) to receive treatment with a biologic diseasemodifying antirheumatic drug (DMARD), and specifically 1 of the 6 tumor necrosis factor antagonists (anti-TNFs), do you have that all-important conversation to determine which modality—infusion therapy (IV) or subcutaneous self-injection (SQ)—is right for them? A recent survey of 243 RA patients and 103 prescribers found discordance between physicians’ assumptions and patients’ actual preferences regarding IV and SQ delivery.1 Although surveyed rheumatologists thought that patients would prefer SQ injections over IV therapy, patients were equally distributed in their preferences, with 16% choosing SQ only and 14% opting for IV therapy only.1 More surprising, 53% of patients were open to trying either therapy, compared with 41% of physicians who made that assumption (Figure 1).1
When these same patients and physicians were asked to allocate 100 points across various biologic therapeutic options and administration schedules according to patient preference, the mean scores demonstrated that patients prefer SQ injections every 4 weeks or monthly ( Table 1). Patients’ second-most preferred option was IV therapy for 30 minutes every 8 weeks. The respondents cited frequency of administration, time to complete an infusion, and site of care as factors in deciding between SQ and IV therapy.1 DISCUSS FIRST, THEN PRESCRIBE Why all the attention to patients’ choosing between SQ and IV therapy? It matters, say the American College of Rheumatologists (ACR) and the European League Against Rheumatism (EULAR), because empowered patients tend to have better outcomes and greater satisfaction.2,3 Preferences may vary according to patients’ age, sex, employment
FIGURE 1. Physicians’ assumptions of patients’ openness to biologic therapeutic choices1
60% 53% Proportion of Patients (%)
10% 0% IV Only
% Patient Reported n=243 rheumatoid arthritis patients
Prescriber Reported Mean % Patients n=103 rheumatologists
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lasting effect (12 months following intervention) in a study of 71 patients with arthritis, as measured by the Global Well-Being Scale and the Arthritis Self-Efficacy Other Symptoms Subscale.13 During the study, patients attended 3-hour group instruction sessions 3 times per week on alternating weeks, followed by a 45-minute individual session.13 In speaking with their RA patients, clinicians need to be aware of the aspects of the disease and its treatment that patients find most troubling so they can tailor their conversations to address the greatest concerns.12 For example, RA patients frequently state that disability, dependency on pharmacotherapy, and long-term adverse effects from medications are the most troubling aspects of their disease.12,14,15
TABLE 1. Patient and prescriber perceptions of patient preferences for attributes of biologic therapies1,* Patient
Self-injection, every 4 weeks or monthly
Intravenous infusion, taking 30 minutes, every 8 weeks
Self-injection, once a week
Self-injection, every 2 weeks
Intravenous infusion, taking 30 minutes, every 4 weeks
Self-injection, twice a week
Intravenous infusion, taking 1 hour, every 4 weeks
Intravenous infusion, taking 2 hours, every 8 weeks
Intravenous infusion, 2 infusions taking 5 hours, separated by 2 weeks, every 16-24 weeks
Intravenous infusion, taking 2 hours, every 4 weeks
Patients and providers were asked to allocate 100 points across biologic options by patient preference.
status, and insurance coverage,1,4 so clinicians would be wise to discuss patients’ individual needs before prescribing (Figure 2). In multiple trials of RA patients, those who were educated about their disease were able to participate more fully in clinical decision-making and therefore were more adherent to their regimens, whether it was pharmacotherapy, physical therapy, or lifestyle changes.5,6 Patients who are more compliant tend to report greater treatment satisfaction and better outcomes.5,6 When patients do ask for further information, be sure to steer them toward reliable, medically sound sources.7 Medication compliance in RA patients ranges from 20% to 50%, underscoring the need for rheumatologists and their colleagues to encourage shared decision-making with patients to promote greater therapeutic compliance.8 Various studies have sought to assess factors affecting positive adherence to RA biologic medication, such as older age, female gender, Caucasian race, and disease severity.9,10 Researchers have suggested that risk factors
Employment Status 90%
Age Group 100%
Not Employed (n=95)
20% 23% 3%
FIGURE 2. Patient-reported openness to mode of administration1,4
<65 Years (n=200)
20% 5.6% 5.6%
≥65 Years (n=43)
Both IV and SQ SQ Only
PATIENT EVALUATION TOOLS One tool to evaluate patients’ attitudes toward therapy and their adherence is the Beliefs about Medicines Questionnaire (BMQ), a validated instrument that has been tested in the RA patient population.14 In a study of 81 patients with RA, the BMQ predicted who was likely to remain adherent with their chosen therapy, based on their belief in the need for medication on the one hand and their concerns about medication side effects on the other.14 When used in the context of other validated patient self-assessments, such as the Arthritis Helplessness Index/Rheumatology Attitudes Index and the Arthritis Self-Efficacy Scale, clinicians can get a better sense of patients’ perspectives about their RA and treatment.16 Once the rheumatology team has assessed those attitudes, they can tailor their counseling to the patient’s individual needs. An often overlooked consideration in patient assessment is health literacy.17 An estimated 21% of American adults are func-
AN OUNCE OF PREVENTION WITH PATIENT EDUCATION Even before discussing specific therapeutic modalities, it’s important to provide basic education on the RA disease process. If patients do not understand the significance of their disease and its progressive nature, they may not feel the need to seek early treatment to slow the disease process, prevent further joint damage, and provide symptom relief.11 By providing patients—and their families— with an understanding of the RA disease state, therapeutic options, and coping mechanisms, clinicians can foster a better working relationship with them as the disease progresses.12,13 Patient education provided by nurses, individually or in groups, was shown to produce a
Insurance Coverage 100%
for noncompliance might include lower education and income levels, more adverse effects, and higher out-of-pocket medication costs, yet only ethnicity, specifically Caucasian race, has so far proved to be a significant factor in predicting adherence.9
IV Only 15.5%
0% Male (n=36)
| Conversations in Rheumatoid Arthritis (RA) Therapy: Choosing Between Subcutaneous Injections and Infusion Therapy
tionally illiterate, which often results in more hospital admissions, greater use of healthcare resources, and poorer health outcomes when compared with those who can comprehend written medical instructions.17 The Rapid Estimate of Adult Literacy in Medicine (REALM) is one such measure that can help evaluate patients’ readiness to assume self-care for their RA. In the REALM test, the patient is asked to read a 66-word list of lay medical terms, arranged according to complexity. In a screen of 127 RA patients tested in the United Kingdom, 15% were able to read fewer than 60 words, indicating that they would struggle with patient education materials and prescription labels and would need materials tailored for people with low literacy.17 Screening patients for literacy might help to reduce their anxiety and the number of phone calls and visits, as well as guide patients toward a modality that is suitable for them. PRESENTING THE THERAPEUTIC OPTIONS By the time your patients need treatment with a biologic agent, you might think they have amassed a wealth of knowledge about RA. It is not necessarily the case. To provide your patient with sufficient information, first be sure they understand the nature of the disease and why they are being prescribed an anti-TNF agent or combination of agents. Involving the patient in the decision-making process is sound clinical practice—and makes good business sense, too. A multisite study of 7730 patients and 300 physicians found that clinicians who involved the patient in therapeutic decision-making had more satisfied patients, and retained more of them as well.6 For example, among patients of physicians with the highest “participation” ratings, only 15% changed physicians within a year; among patients of physicians with the lowest participation scores, one third switched doctors.6 How physicians approach patients is just as important as what they discuss. Younger patients may prefer a more direct style, whereas older patients may prefer a more genteel approach.18 To start the discussion, please see the enclosed patient education sheet. In the self-assessment portion, there is no scoring as the queries are meant to engage the patient in a discussion of the clinical and nonclinical considerations for selecting an appropriate therapeutic option. Though every patient has his or her own concerns, studies of RA patients have found
FIGURE 3. Reasons for patients’ preferences for SQ or IV biologic treatment20
Difficulty/discomfort in reaching hospital Self-administration Painful administration Needle phobia or dislike of needles Safety Reassuring effect of doctor’s presence Interference with everyday life Safety of hospital administration Anxiety about having injections Easy to use Convenience of hospital/home treatment Preparation of drugs Frequency of administration Overall convenience 0
Patient preferences, %
that considerations in selecting a therapy focus on many nonclinical aspects of care (Figure 3). Chief among these are convenience, caregiver considerations, cost/reimbursement, and privacy.19,20 Fear of needles, for example, was not a significant factor in deciding between SQ and IV therapy.20 In reviewing the benefits of both SQ and IV therapy, it is important to individualize treatment—and the discussion. Both the ACR and EULAR recommendations state that treatment must be customized; the guidelines are meant to provide a starting point for therapeutic decision-making.2 To empower patients to make sensible decisions, be sure to include the following information: • Therapeutic rationale for choosing one type of anti-TNF agent over another • Dosing schedule for IV and SQ anti-TNF agents and the time commitments for each • Common adverse effects for SQ and IV therapies • How these drugs may interact with concomitant medications • Routine monitoring for liver abnormalities, tuberculosis, hepatitis B, and other infections. It is important to ensure that patients who have no prior experience in self-injecting biologics understand all the responsibilities that are involved. The first injection is typically administered in the rheumatologist’s office, with instruction by a nurse or physician. After that, patients or their caregivers will be responsible not only for administering the injection at home but also properly storing the injection devices in a refrigerator and safely disposing of them after use (and maintaining the cold chain when they travel).
If they do not understand what they are agreeing to when making a treatment choice, disappointment, fear, and resentment may set in when the expectations become clear. ONCE A CHOICE IS MADE Patients who decide to self-inject anti-TNF medication should spend time with a clinician to be sure they are confident in their self-care. At minimum, patients need to learn about the injection sites in the thigh and abdomen, the importance of rotating them, and proper injection techniques. Ideally, patients should be able to test their injection skills after watching a physician or nurse demonstrate the procedure. If certain self-injectables require diluting the drug, the clinician should be sure that the patient is capable of doing so before being sent home to self-inject for the first time. Injection devices vary for each medication. It’s critical for the patient to understand how to use the specific injection device for the medication prescribed, even if the patient is comfortable with self-injection or has had previous injection experience with other devices. A thorough review of the patient guide, which includes the dosing schedule, storage, and disposal of the syringes, is essential. Patients who have been prescribed infusion therapy should be given a tentative schedule of their appointments, which may be more frequent initially, depending on their individual regimen. They will need to know why it is important that they adhere to a certain schedule. Regardless of the modality chosen, absolutely vital to communicate are the signs of danger that should alert the patient or caregiver to seek immediate medical assistance:
Conversations in Rheumatoid Arthritis (RA) Therapy: Choosing Between Subcutaneous Injections and Infusion Therapy | 3
anaphylaxis, severe pain, rash, and breathing difficulty. It is also critical to schedule regular follow-up visits and phone calls to assure the patient that the healthcare team will monitor for any common adverse effects, such as infections, tuberculosis, and liver abnormalities.2,3 With either modality, clinicians should set appropriate expectations regarding treatment. Some patients may experience a response as early as 2 weeks into treatment, but most patients will likely need more time, up to 3 months. Before anti-TNF therapy begins, patients need to be screened for tuberculosis and hepatitis B, as treatment can exacerbate these conditions.21 Anti-TNF medications are contraindicated in patients with untreated chronic hepatitis B infection and congestive heart failure (New York Heart Association Class III or IV with an ejection fraction ≤50%).2 If patients have not received vaccinations, such as the pneumococcal, influenza intramuscular, hepatitis B, meningococcal, and human papillomavirus vaccines, they should do so before starting treatment.2,3 During treatment with anti-TNF medications, patients should not receive live, attenuated vaccines due to their immunosuppressed state.2 Patients contemplating pregnancy as well as breastfeeding should not continue antiTNF therapy.22 They should know that pregnancy may have a temporary salutary effect on the disease, but flare-ups can re-emerge postpartum.22 ONGOING SUPPORT IS ESSENTIAL At follow-up visits, patients need to be reminded that their immune systems are vulnerable to bacterial, fungal, and viral infections.2 Patients taking anti-TNF drugs are also susceptible to respiratory infections and to lymphoma and skin cancers as well.21 Discuss with your patients how you will measure success and how often they will need to return to the office for follow-up visits and lab tests. The Rheumatoid Arthritis Disease Activity Index is one such measure that can determine whether the selected therapy or combination of therapies is effective.2,23 In addition to using validated efficacy scales, it is helpful to develop mutually agreedupon goals with your patients and ask candid follow-up questions as to whether they are
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progressing as well as they thought they would. Maintaining a dialogue with your RA patients is essential to therapeutic success.24 Even after a thoughtful discussion of the benefits of either IV or SQ therapy, patients may request a switch to another form of treatment. Clinical teams can lessen this possibility by counseling patients throughout their course of treatment, whereby pharmacists and nurses follow up with them.25 When a switch in medications is under consideration, patients may be reluctant to change, citing fear of side effects or a concern that the new medication might not work as well and they would lose control of their arthritis.15 In a study of 6135 patients with RA, 77% said they were satisfied with their current regimen, and 63.8% said they would want to continue with their current medication as long as their condition didn’t worsen. The study group included patients receiving biologic agents and patients receiving other types of RA medications.15 Even patients who do not appear to have improved on a given regimen may say they are satisfied with their treatment because having the disease relatively stabilized may be a factor in their therapeutic satisfaction.15, 26 Clinicians who maintain a solid, trusting relationship with their RA patients may promote better outcomes and more satisfied patients.26 REFERENCES 1. Bolge SC, Brown D, Goren A, et al. Openness to and preference for biologic therapy among patients with rheumatoid arthritis prior to biologic initiation: patient and prescriber perspectives. Poster presented at: American College of Rheumatology Annual Meeting; October 28, 2013; San Diego, CA. Abstract 1023. 2. Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639. 3. Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509. 4. Janssen Biotech, Inc. Data on File. Openness to IV—patient demographics. 2013. 5. Elwyn G, Edwards A, Kinnersley P. Shared decision-making in primary care: the neglected second half of the consultation. Br J Gen Pract. 1999;49(443):477-482. 6. Kaplan SH, Greenfield S, Gandek B, Rogers WH, Ware JE Jr. Characteristics of physicians with participatory decisionmaking styles. Ann Intern Med. 1996;124(5):497-504. 7. Garneau K, Iversen M, Jan S, Parmar K, Tsao P, Solomon DH. Rheumatoid arthritis decision making: many information sources but not all rated as useful. J Clin Rheumatol. 2011;17(5):231-235. 8. van den Bemt BJ, van den Hoogen FH, Benraad B, et al. Adherence rates and associations with nonadherence in
patients with rheumatoid arthritis using disease modifying antirheumatic drugs. J Rheumatol. 2009;36(10):2164-2170. 9. Salt E, Frazier SK. Predictors of medication adherence in patients with rheumatoid arthritis. Drug Dev Res. 2011;72(8):756-763. 10. Viller F, Guillemin F, Briancon S, Moum T, Suurmeijer T, van der Heuvel W. Compliance to drug treatment of patients with rheumatoid arthritis: a 3-year longitudinal study. J Rheumatol. 1999;26(10):2114-2122. 1 1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on health: rheumatoid arthritis. http://www.niams.nih.gov/Health_Info/Rheumatic_Disease/default.asp. Accessed January 27, 2014. 1 2. da Mota LM, Cruz BA, Brenol CV, et al. 2012 Brazilian Society of Rheumatology consensus for the treatment of rheumatoid arthritis. Rev Bras Reumatol. 2012;52(2): 135-174. 1 3. Grønning K, Rannestad T, Skomsvoll JF, Rygg LO, Steinsbekk A. Long-term effects of a nurse-led group and individual patient education programme for patients with chronic inflammatory polyarthritis—a randomised controlled trial. J Clin Nurs. 2013 Jul 22. [Epub ahead of print] 14. Neame R, Hammond A. Beliefs about medications: a questionnaire survey of people with rheumatoid arthritis. Rheumatology. 2005;44(6):762-767. 1 5. Wolfe F, Michaud K. Resistance of rheumatoid arthritis patients to changing therapy: discordance between disease activity and patients’ treatment choices. Arthritis Rheum. 2007;56(7):2135-2142. 16. Brady TJ. Measures of self-efficacy, helplessness, mastery, and control: the Arthritis Helplessness Index (AHI)/Rheumatology Attitudes Index (RAI), Arthritis Self-Efficacy Scale (ASES), Children’s Arthritis SelfEfficacy Scale (CASE), Generalized Self-Efficacy Scale (GSES), Mastery Scale, Multi-Dimensional Health Locus of Control Scale (MHLC), Parent’s Arthritis Self-Efficacy Scale (PASE), Rheumatoid Arthritis Self-Efficacy Scale (RASE), and Self-Efficacy Scale (SES). Arthritis Care Res (Hoboken). 2003;49(5S):S147-S164. 17. Gordon MM, Hampson R, Capell HA, Madhok R. Illiteracy in rheumatoid arthritis patients as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) score. Rheumatology (Oxford). 2002;41(7):750-754. 1 8. Herndon JH, Pollick KJ. Continuing concerns, new challenges, and next steps in physician-patient communication. J Bone Joint Surg Am. 2002;84-A(2):309-315. 19. Curkendall S, Patel V, Gleeson M, et al. Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter? Arthritis Rheum. 2008;59(10):1519-1526. 20. Scarpato S, Antivalle M, Favalli EG, et al. Patient preferences in the choice of anti-TNF therapies in rheumatoid arthritis: results from a questionnaire survey (RIVIERA study). Rheumatology (Oxford). 2010;49(2):289-294. 21. American College of Rheumatology. Anti-tumor necrosis factor fact sheet. http://www.rheumatology.org/Practice/Clinical/Patients/Medications/Anti-TNF/. Accessed January 24, 2014. 22. American College of Rheumatology. Pregnancy and rheumatic disease. http://www.rheumatology.org/ Practice/Clinical/Patients/Diseases_And_Conditions/ Pregnancy_and_Rheumatic_Disease/. Accessed January 24, 2014. 23. Barton JL, Imboden J, Graf J, Glidden D, Yelin EH, Schillinger D. Patient-physician discordance in assessments of global disease severity in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010;62(6):857-864. 24. Ryan S, Hassell A, Dawes P, Kendall S. Control perceptions in patients with rheumatoid arthritis: the impact of the medical consultation. Rheumatology (Oxford). 2003;42(1):135-140. 25. Stockl KM, Shin JS, Lew HC, et al. Outcomes of a rheumatoid arthritis disease therapy management program focusing on medication adherence. J Manag Care Pharm. 2010;16(8):593-604. 26. Mulley AG, Trimble C, Elwyn G. Stop the silent misdiagnosis: patients’ preferences matter. BMJ. 2012;345:e6572.
Patient Self-Assessment for Rheumatoid Arthritis Biologic Therapies Please consider the following questions, which are meant to help you and your rheumatologist in selecting how to receive your treatment for rheumatoid arthritis.Your responses will help determine whether infusion at your doctor’s office or clinic, or self-injection at home, is better suited to you. In discussing treatment with your doctor, consider these factors and check the box at the bottom to indicate whether treatment by infusion or self-injection is best for you.
How often will I need treatment? n
Infusion treatment may be administered as often as once a month or less often, depending upon the
medication. Infusion time varies by medication. Self-injection treatment can be done by you or a caregiver, after training from your doctor or nurse, as often as once a week or less often, depending upon the medication.
Where will my treatment take place? n
Infusion is prepared and given by a healthcare professional at a doctor’s office or infusion center.
Self-injection is prepared and given by you or your caregiver in your home, requiring you to keep all the
medication and supplies on hand.
How will my treatment be administered? n
Infusion is prepared and given by a healthcare professional through a needle placed in a vein, usually in your
arm for 30 minutes. For self-injection treatment, you will prepare and give yourself an injection just below the surface of your skin in your abdomen or thigh, after training by your doctor or nurse.
Your confidence and comfort level n
Do you feel you could self-inject on your own, after training from your doctor or nurse?
Do you feel comfortable identifying if you have an infection? If you have an infection, you will need to check
with your doctor to see if it’s okay to receive biologic treatment.
Support and safety n
Do you have any physical limitations that might interfere with your ability to self-inject?
Do you have support at home to help you if you need it?
Are you comfortable with securing your medication from the pharmacy before each self-injection?
Do you have a good place to safely store your medication in your refrigerator, out of reach of children?
Do you have a safe place to store a sharps disposal container with used syringes, out of the reach of children
Your preference? Taking all of the above into consideration, do you prefer to: n Receive treatments administered directly by a healthcare professional at your doctor’s office or infusion center? OR n Self-inject on your own, at home?
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You inject yourself after proper training by a doctor or nurse
Infusion is prepared and given by a doctor, nurse, or trained healthcare professional
You fill the prescription and store medication in refrigerator
Your doctor prescribes and a healthcare professional stores your medication until your infusion
Treatment is usually self-injected at home
Treatment is given at your doctorâ€™s office or infusion center
Injected under the skin of your abdomen or thigh
30-minute infusion through a needle placed in a vein, usually in your arm
Frequency varies (once a week or less often), depending on the medication used
As often as once a month or less often, depending on the medication used
Prefilled injection device with fixed amount of medication for each dose
Amount of medication for each dose based on your weight
Taken with methotrexate, depending on medication, as directed
Taken with methotrexate, as directed
Before you begin treatment, tell your doctor if you have, or have had: Special considerations
Requires training Manual dexterity n Good vision n Refrigerator to store medication before use n Container to safely dispose of used syringe n
Ability to travel to appointments
Before you begin treatment, tell your doctor if you: n n
n n n
n n n n
ave an infection* H Have or have had lymphoma or any other type of cancer Have or have had heart failure Have or have had hepatitis B Have or have had a condition that affects your nervous system, such as multiple sclerosis or Guillain-Barre syndrome Have recently received or are scheduled to receive a vaccine Are pregnant or planning to become pregnant Are breastfeeding Have diabetes, HIV, or a weak immune system Get a lot of infections or have infections that keep coming back
Have tuberculosis (TB) or have been in close contact with someone with TB Use the medicine ORENCIA (abatacept), KINERET (anakinra), ACTEMRA (tocilizumab), or RITUXAN (rituximab) Live, have lived, or have traveled to certain parts of the country (Ohio and Mississippi River valleys and the Southwest) where there is an increased risk for getting certain types of fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis). Have a baby and used this medication during your pregnancy
*Symptoms of an infection may include fever, sweat or chills; muscle aches; cough; shortness of breath; blood in phlegm; weight loss; warm, red, or painful skin or sores on your body; diarrhea or stomach pain; burning when you urinate or urinate more often than normal; feeling very tired.
For full details on what to tell your doctor, before you begin treatment and after treatment is in progress, see the Medication Guide for the product that your doctor has prescribed for you. The US Food and Drug Administration requires that Medication Guides be provided with certain prescribed drugs and biologic products. REFERENCES Agency for Healthcare Quality and Research. Medicines for rheumatoid arthritis: a review of the research for adults. AHRQ Pub. No. 12(13)-EHC025-A. November 2012. American College of Rheumatology. Anti-tumor necrosis factor fact sheet. http://www.rheumatology.org/Practice/Clinical/Patients/Medications/AntiTNF/. Accessed January 15, 2014. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on health: rheumatoid arthritis. http://www.niams.nih.gov/Health_Info/ Rheumatic_Disease/default.asp. Accessed January 21, 2014.
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