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Rheumatoid Arthritis Medication

  • Author: Howard R Smith, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jul 19, 2016
 

Medication Summary

Optimal care of patients with rheumatoid arthritis (RA) requires an integrated approach that includes both nonpharmacologic therapies and pharmacologic agents such as nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and corticosteroids.

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DMARDs, Other

Class Summary

DMARDs represent the most important measure in the successful treatment of rheumatoid arthritis. These agents can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function. Successful DMARD therapy may eliminate the need for other anti-inflammatory or analgesic medications; however, until the full action of DMARDs takes effect, anti-inflammatory or analgesic medications may be required as bridging therapy to reduce pain and swelling.

Leflunomide (Arava)

 

Leflunomide is indicated for the treatment of active RA to reduce signs and symptoms, inhibit structural damage and improve physical function. Corticosteroids, aspirin, or other NSAIDs may be continued during leflunomide use. Leflunomide is contraindicated in women who are or may become pregnant.

Leflunomide is a pyrimidine synthesis inhibitor that blocks autoimmune antibodies and reduces inflammation. It also inhibits dihydroorotate dehydrogenase, an enzyme in the de novo pyrimidine synthesis pathway and has antiproliferative activity. Complete blood counts (CBCs) and liver enzymes must be monitored.

Sulfasalazine (Azulfidine, Azulfidine EN-tabs)

 

Sulfasalazine (SSZ) is indicated for the treatment of patients with RA who have had an inadequate response to salicylates or other NSAIDs. It acts locally to decrease inflammatory response and systemically inhibits prostaglandin synthesis.

SSZ delayed-release tablets do not have an immediate response; therefore, concurrent treatment with NSAIDs or other analgesics is recommended at least until the effect of the delayed-release tablets is apparent. The initial dosage is 0.5-1 g/day. The dosage can be adjusted to a dose of 3 g/day after 12 weeks if an adequate clinical response is not seen.

Hydroxychloroquine (Plaquenil)

 

Hydroxychloroquine (HCQ) is approved for the treatment of acute or chronic RA. The initial dosage is 400-600 mg/day; dosages should be computed on the basis of patient body weight. If a good clinical response is seen over a period of 4 to 12 weeks, the dosage can be reduced by 50% and continued at a level of 200-400 mg/day. The risk of retinopathy is greater when this dosage is exceeded. It should be noted that each 200 mg tablet contains only 155 mg of active drug.

Patients must have a baseline eye examination (including color and vision testing, funduscopic examination, and visual-field testing) performed before starting HCQ therapy. Most rheumatologists recommend an HCQ eye examination every 6-12 months.

Rituximab (Rituxan)

 

Rituximab is most often used in combination with methotrexate (MTX). It has been shown to be effective at reducing signs and symptoms in adult patients with moderately to severely active RA who have had an inadequate response to therapy with 1 or more tumor necrosis factor (TNF) antagonists. Treatment with rituximab may deplete CD20+ B cells. The usual regimen consists of 2 intravenous (IV) infusions of 1000 mg, separated by 2 weeks, in combination with MTX.

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DMARDs, Immunomodulators

Class Summary

DMARDs represent the most important measure in the successful treatment of RA.

Azathioprine (Imuran)

 

Although azathioprine is not a first-line agent, it is sometimes used in the treatment of active RA to reduce signs and symptoms, particularly in patients who may have coinciding connective tissue diseases, such as systemic lupus erythematosus. Aspirin, NSAIDs, or low-dose glucocorticoids may be continued during treatment with azathioprine. The mechanism whereby azathioprine affects autoimmune diseases is unknown; however, it works primarily on T cells.

The initial dosage is 1 mg/kg/day (50-100 mg/day) given as a single dose or in divided doses twice daily. The dosage may be increased by 0.5 mg/kg/day at 6-8 weeks and thereafter at 4-week intervals, up to a maximum dosage of 2.5 mg/kg/day. Azathioprine is available in tablet form for oral administration or in 100-mg vials for IV injection.

Tocilizumab (Actemra)

 

Tocilizumab is an IL-6 receptor inhibitor. It is indicated for moderate to severe active RA in adults who have had an inadequate response to 1 or more TNF-antagonist therapies. It has been approved as an IV infusion or SC injection that may be used alone or in combination with MTX or other DMARDs. The usual dosage for IV infusion is 4 mg/kg once every 4 weeks, with a maximum dose of 800 mg per infusion. The usual dose for SC injection is 162 mg given every other week, then increased to every week for patients < 100 kg, or 162 mg given every week for patients≥100 kg.

Tofacitinib (Xeljanz)

 

Tofacitinib is an oral Janus kinase (JAK) pathways inhibitor. It is indicated as second-line treatment for moderate to severe active RA in patients with an inadequate response to or intolerance of MTX. Tofacitinib may be used as monotherapy or in combination with MTX or other nonbiologic DMARDs, but it should not be used in combination with biologic DMARDs or potent immunosuppressive agents (eg, azathioprine and cyclosporine).

Cyclosporine (Gengraf, Sandimmune, Neoral, cyclosporin A)

 

Although cyclosporine is approved for the treatment of patients with severe active RA in which the disease has not adequately responded to MTX, it is not commonly used to treat RA, because of its nephrotoxicity. When cyclosporine is used, patients' renal function must be closely monitored.

Cyclosporine can be used in combination with MTX in RA patients who do not have an adequate response to MTX alone. The initial dosage is 2.5 mg/kg/day divided twice daily. The onset of action generally occurs between 4 and 8 weeks. The dosage may be titrated to a maximum of 4 mg/kg/day.

Methotrexate (Rheumatrex, Trexall, Otrexup)

 

MTX is a folic acid antagonist that is approved for the management of severe active RA in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of first-line therapy, including full-dose NSAIDs. MTX is started at lower doses and increased to full doses within approximately 4-6 weeks. The initial dosage is 7.5 mg/wk PO in a single dose; alternatively, the weekly regimen may be administered in divided doses of 2.5 mg PO at 12-hour intervals for 3 doses. A self- administered subcutaneous injection is also available (Otrexup), and may improve bioavailability and avoid GI effects for patients who need higher doses.

The CBC should be monitored monthly and liver and renal function every 1-3 months during therapy (though American College of Rheumatology [ACR] guidelines indicate that it may be safe to monitor liver function every 3-4 months).

MTX is contraindicated in pregnancy, because it is an abortifacient and has teratogenic effects, including craniofacial abnormalities, limb defects, and central nervous system (CNS) defects such as anencephaly, hydrocephaly, and meningomyelopathy, especially with first-trimester exposure.

Anakinra (Kineret)

 

Anakinra is a recombinant, nonglycosylated form of the human interleukin (IL)-1 receptor antagonist (IL-1Ra) that is indicated for reducing signs and symptoms and slowing the progression of structural damage of moderately to severely active RA that has failed treatment with 1 or more DMARDs. Anakinra can be used alone or in combination with DMARDs other than TNF-blocking agents.

The initial dosage is 100 mg/day subcutaneous (SC) injection. However, anakinra is not commonly used to treat RA, because of its relative inefficacy. It is more often used to treat juvenile idiopathic arthritis (JIA) and periodic fever syndromes.

Abatacept (Orencia)

 

Abatacept is a selective costimulation modulator that inhibits T-cell activation by binding to CD80 and CD86, thereby blocking their interaction with CD28. CD28 interaction provides a signal needed for the full T-cell activation that is implicated in RA pathogenesis.

This agent is approved for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. Abatacept can be used as monotherapy or concomitantly with DMARDs other than TNF antagonists.

Abatacept is dosed according to body weight; after the initial IV infusion, it is repeated at week 2 and week 4 and then every 4 weeks. Maintenance doses may be administered as a monthly IV infusion or by the patient as a weekly SC injection.

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DMARDs, TNF Inhibitors

Class Summary

The recognition of TNF-α and IL-1 as central proinflammatory cytokines has led to the development of agents that block either these cytokines or their effects. In addition to improving signs and symptoms and quality of life, all biologic agents significantly retard radiographic progression of joint erosions.

The TNF inhibitors, which bind TNF and thus prevent its interaction with its receptors, include etanercept, infliximab, golimumab, certolizumab, and adalimumab. Consensus statements do not recommend their use until at least one xenobiotic DMARD, usually MTX, has been administered without sufficient success.

Adverse effects associated with the biologic agents include the generation of antibodies against these compounds, the emergence of antinuclear antibodies (ANAs), occasional drug-induced lupuslike syndromes, and infections. Rarely, demyelinating disorders and bone marrow suppression occur.

Acute and chronic infections, demyelinating disorders, New York Heart Association (NYHA) class III or IV heart failure, and recent malignancies are contraindications for the use of TNF inhibitors. A thorough search for latent tuberculosis using chest radiography or purified protein derivative (PPD) testing is recommended before these agents are started. Patients taking anti-TNF agents must avoid live-virus vaccines to avoid the risk of serious infection.

Infliximab (Inflectra, Remicade)

 

Infliximab, a chimeric monoclonal antibody against TNF-α, is approved for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active RA, in combination with MTX. This agent binds to cells that express membrane TNF. Infliximab is administered at doses of 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with MTX.

Etanercept (Enbrel)

 

Etanercept, a bivalent p75–TNF receptor linked to the Fc portion of human immunoglobulin G (IgG), is approved for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active RA. It can be given alone or in combination with MTX. This agent binds lymphotoxin (formerly termed TNF-β) in addition to soluble TNF-α. The usual dosage is 25 mg SC twice weekly or 50 mg SC weekly, with or without concomitant MTX.

Golimumab (Simponi, Simponi Aria)

 

Golimumab, a human monoclonal antibody to TNF-α, inhibits TNF-α bioactivity, thereby modulating immune activity in patients with RA. It is approved for the treatment of adults with moderately to severely active RA, in combination with MTX. It may be administered as either a SC injection every month, or as an IV infusion every 2 months following 2 once monthly doses. Golimumab should be given in combination with MTX.

Certolizumab (Cimzia)

 

Certolizumab is a pegylated anti−TNF-α agent, which results in disruption of the inflammatory process in RA. It is indicated for the treatment of adults with moderately to severely active RA. The standard regimen consists of an initial dose of 400 mg and 2 subsequent doses of 400 mg at weeks 2 and 4 (given as 2 SC injections of 200 mg), followed by 200 mg every other week.

Adalimumab (Humira)

 

Adalimumab is indicated to reduce inflammation and inhibit progression of structural damage in moderate to severe RA, alone or in combination with MTX or other nonbiologic DMARDs. This agent is reserved for those who experience an inadequate response to 1 or more DMARDs. Adalimumab can be used alone or in combination with MTX or other DMARDs.

Adalimumab is a recombinant human IgG1 monoclonal antibody that is specific for human TNF. It binds specifically to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors.

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Tetracyclines

Class Summary

Although tetracyclines are not typically used to treat RA, the ACR recommends minocycline monotherapy in patients with a disease duration shorter than 24 months who have low disease activity and no poor prognostic factors.[68, 4]

Minocycline (Dynacin, Minocin)

 

The minocycline regimen that is most commonly used in RA is 100 mg twice daily for up to 2 years. The anti-inflammatory effects of minocycline may result from inhibition of inflammatory cell migration and transformation of lymphocytes.

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Nonsteroidal Anti-inflammatory Drugs

Class Summary

NSAIDs interfere with prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX), thus reducing swelling and pain. However, they do not retard joint destruction and therefore are not sufficient to treat RA when used alone. Like corticosteroids, NSAIDs can be reduced in dose or discontinued with successful DMARD therapy. These agents decrease intraglomerular pressure and decrease proteinuria.

The several dozen NSAIDs available can be classified into several different groups of compounds. Commonly used NSAIDs include ibuprofen, naproxen, ketoprofen, celecoxib, and diclofenac.

Ibuprofen (Motrin, Advil)

 

Ibuprofen is indicated for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Naprosyn, Aleve, Anaprox, Anaprox DS, Naprelan)

 

Naproxen is used to relieve mild to moderate pain. This agent inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Diclofenac (Voltaren, Cataflam)

 

Diclofenac is one of a series of phenylacetic acids that have demonstrated anti-inflammatory and analgesic properties in pharmacologic studies. It is believed to inhibit COX, which is essential in the biosynthesis of prostaglandins.

Diclofenac can cause hepatotoxicity; therefore, liver enzymes should be monitored in the first 8 weeks of treatment. This agent is absorbed rapidly; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. The delayed-release, enteric-coated form is diclofenac sodium, and the immediate-release form is diclofenac potassium.

Ketoprofen (Orudis, Oruvail)

 

Ketoprofen is used to relieve mild to moderate pain and inflammation. Small dosages are initially indicated in small and elderly patients and in those with renal or liver disease. Doses higher than 75 mg do not yield increased therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Celecoxib (Celebrex)

 

Celecoxib is approved for the relief of signs and symptoms of RA. It primarily inhibits COX-2, which is considered an inducible isoenzyme (induced during pain and inflammatory stimuli). Inhibition of COX-1 may contribute to NSAID gastrointestinal (GI) toxicity. At therapeutic concentrations, celecoxib does not inhibit COX-1, thus potentially resulting in decreased GI toxicity. Administer the lowest possible dose for each patient. Use of celecoxib has been associated with an increased risk of cardiovascular toxicity.

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Analgesics, Other

Class Summary

Analgesics such as acetaminophen may be used in patients with RA.

Acetaminophen (Tylenol, Aspirin-Free Anacin)

 

Acetaminophen is used for analgesia in patients with documented hypersensitivity to aspirin or NSAIDs, those with upper GI disease, and those who are taking oral anticoagulants. This agent does not have anti-inflammatory properties.

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Opioid Analgesics

Class Summary

Tramadol has been used to reduce pain in patients with RA. However, this agent only provides analgesic effects and does not have anti-inflammatory properties.

Tramadol (Ultram, Ultram ER)

 

The immediate-release formulation of tramadol is approved for the management of moderate to moderately severe pain in adults. The extended-release formulation is used for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of pain for an extended period of time.

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Topical Skin Products

Class Summary

Topical agents such as diclofenac can provide analgesia for patients with RA. This agent is commonly used in patients who experience acute pain.

Diclofenac topical (Voltaren)

 

Diclofenac topical gel is approved in patients with osteoarthritis at a dosage of 32 g/day applied over all affected joints. It has also been used to provide analgesic effects in patients with RA.

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Corticosteroids

Class Summary

Corticosteroids are potent anti-inflammatory drugs commonly used in patients with RA to bridge the time until DMARDs become effective. Prednisone dosages as high as 10 mg/day are typically used, but some patients may require even higher dosages. Adverse events associated with long-term steroid use make dose reductions and cessation important in due course.

Prednisone (Prednisone Intensol, Sterapred, Rayos)

 

Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Circadian (ie, bedtime) administration of modified-release prednisone (Rayos) has been shown shown to decrease morning stiffness with RA.

Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol)

 

Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes (PMNs) and reversing increased capillary permeability.

Prednisolone

 

Prednisolone controls or prevents inflammation by controlling the rate of protein synthesis, suppressing the migration of PMNs and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at the cellular level.

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Chelators

Class Summary

Chelation therapy in RA may suppress inflammation and arthritis by depressing T-cell activity.

Penicillamine (Cuprimine, Depen)

 

Penicillamine depresses circulating IgM rheumatoid factor and T-cell activity (but not B-cell activity).

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Contributor Information and Disclosures
Author

Howard R Smith, MD Director of the Lupus Clinic, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic

Howard R Smith, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Adam Brown, MD Fellow, Department of Rheumatology, Cleveland Clinic

Adam Brown, MD is a member of the following medical societies: American College of Rheumatology, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Katherine K Temprano, MD Assistant Professor of Internal Medicine, Division of Rheumatology, St Louis University School of Medicine

Katherine K Temprano, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American College of Rheumatology

Disclosure: Partner received honoraria from Baxter for speaking and teaching.

Acknowledgements

Edward Bessman, MD Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine

Edward Bessman, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sarjoo M Bhagia, MD Consulting Staff, OrthoCarolina; Voluntary Teaching Faculty, Carolinas Rehabilitation

Sarjoo M Bhagia, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, North American Spine Society, and Physiatric Association of Spine, Sports and Occupational Rehabilitation

Disclosure: Nothing to disclose.

Heather Lyn Carone, MD Attending Physician, Department of Emergency Medicine, St Vincent Mercy Medical Center

Heather Lyn Carone, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Patrick M Foye, MD Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Patrick M Foye, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society

Disclosure: Nothing to disclose.

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Kavita Gupta, DO, MEng Department of Orthopedics, Center of Physical Medicine and Rehabilitation, University of Dentistry and Medicine of New Jersey

Kavita Gupta, DO, MEng is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Osteopathic Association, Association of Academic Physiatrists, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

John A Kare, MD Assistant Professor of Emergency Medicine, Charles R Drew University of Medicine and Science/UCLA, Director of Research, Department of Emergency Medicine, Martin Luther King Jr/Charles R Drew Medical Center

John A Kare, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Student Association/Foundation, and Emergency Medicine Residents Association

Disclosure: Nothing to disclose.

Randall W King, MD, FACEP Assistant Clinical Professor of Emergency Medicine, The University of Toledo College of Medicine; Director, Emergency Medicine Residency Program, Associate Chair, Department of Emergency Medicine, St Vincent Mercy Medical Center

Randall W King, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, Ohio State Medical Association, and Society for Academic Emergency Medicine

Disclosure: Challenger corporation None Physician Advisory Board; Ohio ACEP Consulting fee Editor Rivers review text Emergency Medicine

Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital

Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Robert J Nowinski, DO Clinical Assistant Professor of Orthopaedic Surgery, Ohio State University College of Medicine and Public Health, Ohio University College of Osteopathic Medicine; Private Practice, Orthopedic and Neurological Consultants, Inc, Columbus, Ohio

Robert J Nowinski, DO is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Osteopathic Surgeons, American Medical Association, American Osteopathic Association, Ohio Osteopathic Association, and Ohio State Medical Association

Disclosure: Tornier Grant/research funds Other; Tornier Honoraria Speaking and teaching

Robert E O'Connor, MD, MPH Professor and Chair, Department of Emergency Medicine, University of Virginia Health System

Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Elizabeth Salt, ARPN, PhD Assistant Professor, Division of Rheumatology, University of Kentucky College of Nursing; Rheumatology Nurse Practitioner, University of Kentucky Chandler Medical Center

Elizabeth Scarbrough, MSN is a member of the following medical societies: American College of Rheumatology, Council for the Advancement of Nursing Science, and Sigma Theta Tau International

Disclosure: Nothing to disclose.

Roberto Sandoval, MD Consulting Staff, Department of Emergency Medicine, Anaheim Memorial Medical Center, La Palma Intercommunity Hospital

Roberto Sandoval, MD is a member of the following medical societies: American College of Emergency Physicians and American Medical Association

Disclosure: Nothing to disclose.

Joseph E Sheppard, MD Professor of Clinical Orthopedic Surgery, Chief of Hand and Upper Extremity Service, Department of Orthopedic Surgery, University of Arizona Health Sciences Center, University Physicians Healthcare

Joseph E Sheppard, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Society for Surgery of the Hand, and Orthopaedics Overseas

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Roman V Voytsekhovskiy, MD Fellow in Hand Surgery, Department of Orthopedic Surgery, Rush University Medical Center

Disclosure: Nothing to disclose.

Eleby R Washington III, MD, FACS Associate Professor, Department of Surgery, Division of Orthopedics, Charles R Drew University of Medicine and Science

Eleby R Washington III, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, International College of Surgeons, and National Medical Association

Disclosure: Nothing to disclose.

Richard Worthington MD, Department of Emergency Medicine, Wood County Hospital

Richard Worthington is a member of the following medical societies: American College of Emergency Physicians, Ohio State Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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Ankylosis in the cervical spine at several levels due to long-standing juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).
Widespread osteopenia, carpal crowding (due to cartilage loss), and several erosions affecting the carpal bones and metacarpal heads in particular in a child with advanced juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).
Rheumatoid changes in the hand. Photograph by David Effron MD, FACEP.
Rheumatoid nodules at the elbow. Photograph by David Effron MD, FACEP.
Soft-tissue swelling and early erosions in the proximal interphalangeal joints in a patient with rheumatoid arthritis of the hands.
Subluxation in the metacarpophalangeal joints, with ulnar deviation, in a patient with rheumatoid arthritis of the hands.
Coronal, T1-weighted magnetic resonance imaging scan shows characteristic pannus and erosive changes in the wrist in a patient with active rheumatoid arthritis. Courtesy of J. Tehranzadeh, MD, University of California at Irvine.
Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.
Boutonniere deformity.
Anteroposterior radiograph of the knee shows uniform joint-space loss in the medial and lateral knee compartments without osteophytosis. A Baker cyst is seen medially (arrowhead).
Ultrasonography-guided synovial biopsy of the second metacarpophalangeal joint of the right hand in a patient with rheumatoid arthritis of the hands. The biopsy needle is seen as a straight echogenic line on the left side of the image in an oblique orientation.
Plain lateral radiograph of the normal cervical spine taken in extension shows measurement of anterior atlantodental interval (yellow line) and posterior atlantodental interval (red line).
Lateral flexion view of the cervical spine shows atlantoaxial subluxation.
Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.
T1-weighted sagittal magnetic resonance image of the cervical spine shows basilar invagination with cranial migration of an eroded odontoid peg. There is minimal pannus. The tip of the peg indents the medulla, and there is narrowing of the foramen magnum due to the presence of the peg. Inflammatory fusion of several cervical vertebral bodies is shown.
Sagittal T2-weighted magnetic resonance image of cervical spine in same patient as in previous image. Compromised foramen magnum is easily appreciated, and there is increased signal intensity within upper cord; this is consistent with compressive myelomalacia. Further narrowing of canal is seen at multiple levels.
Lateral radiograph of the same patient as in Images 4-5. Midcervical vertebral-body fusions are shown. The eroded peg is difficult to visualize, but inferior subluxation of the anterior arch of C1 is shown.
Lateral radiograph of a normal cervical spine shows the McGregor line. The odontoid tip should not protrude more than 4.5 mm above the line, which is drawn from the posterior edge of the hard palate to the most caudal point of the occiput.
Normal lateral magnified radiograph of the cervical spine shows the Ranawat method of detection of cranial settling. This method is used to measure the distance from the center of the pedicles (sclerotic ring) of C2 to a line drawn connecting the midpoints of the anterior and posterior arches of C1. (Normal values are 15 mm or greater for males and 13 mm or greater for females.)
Lateral radiograph of the cervical spine shows how the cervical height index (CHI) is calculated. The distance from the center of the sclerotic ring of C2 to the tip of the spinous process of C2 (dotted line) is measured. This is then divided into the distance from the center of the sclerotic ring of C2 to the midpoint of the inferior border of the body of C7. A CHI of less than 2 mm is a sensitive predictor of neurologic deficit.
X-ray shows total hip replacement, with prosthesis, in patient with osteoarthritis.
This gross photo shows destruction of the cartilage and erosion of the underlying bone with pannus from a patient with rheumatoid arthritis.
The hallmark of rheumatoid arthritis is a perivascular mononuclear cell infiltrate in the synovium (pictured here). The early stages are noted to have plasma cells as well, and syphilis needs to be part of the differential diagnosis.
The inflammation involved in rheumatoid arthritis can be intense. It is composed of mononuclear cells and can resemble a pseudosarcoma.
A 72-year-old man with long-standing rheumatoid arthritis (RA) developed blue-grayish discoloration of his skin. He had been on hydroxychloroquine for approximately 15 years. The diagnosis was hydroxychloroquine-related hyperpigmentation. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is RA nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is RA nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
Table 1. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Disease Activity Recommendations
Early RA (<6 months)
  • Administer DMARD monotherapy in patient with low-high disease activity
  • If disease activity remains moderate /high despite DMARD monotherapy use combination DMARDs OR a TNFi OR a non TNF biologic
(Notable change from 2012 to 2015 guidelines: The 2015 guidelines do not recommend initial combination DMARD therapy in early RA with moderate to high disease activity)
Established RA (=6 month or meets 1987 ACR RA classification criteria) If disease activity remains moderate or high despite DMARD monotherapy, ACR guidelines recommend one of the following:



  • Combination DMARDs
  • Add an anti-TNF biologic
  • Non-TNF biologic
  • Tofacitinib
  



If disease activity remains moderate or high despite use of a single anti-TNF biologic:
  • Switch to a non-TNF biologic  with or without MTX over another anti-TNFi or Tofacitinib
If disease activity remains moderate or high despite use of one anti-TNF biologic and one non-TNF biologic:
  • Use another non-TNF biologic with or without MTX over Tofacitinib
  • If still uncontrolled use Tofacitinib
(Notable change from 2012 to 2015 guidelines: Instead of switching from one anti-TNF biologic to another anti-TNF biologic because of continued activity, it is recommended to change first to a non-TNF biologic)
   
Table 2. 2015 ACR Recommendations for Further Evaluation After Initial/Repeat TB Screening Results
Result of Initial/Repeat TST or IGRA Recommendation
Positive
  • Obtain chest x-ray
  • If the chest x-ray is suspicious for active TB, obtain sputum examination for active disease
Negative In patients with RA but without risk factors or clinical suspicion for TB
  • No further workup is needed
In patients with RA and immunosuppression plus LTBI risk factors
  • LBTI is not excluded
  • Repeat the TST or IGRA 1-3 wk after an initial negative test result
Active/latent TB
  • Treat with appropriate antitubercular therapy
  • Refer to a specialist as necessary
  • Initiate or resume biologic agents after either 1 mo of treatment of LTBI with antitubercular regimen or completion of treatment for active TB
  • Screen annually in individuals with RA who (1) are continuing on biologic agents while living, traveling, or working in situations of likely TB exposure and (2) have a positive baseline for TST or IGRA; TST or IGRA may still be positive after successful TB therapy; monitor for clinical signs or symptoms of recurrent TB
ACR = American College of Rheumatology; IGRA = interferon gamma release assay; LBTI = latent tuberculosis infection; RA = rheumatoid arthritis; TB = tuberculosis; TST = tuberculin skin test.



Source:  Singh JA, Saag KG, et al2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care and Research http://dx.doi.org/10.1002/art.39480 (2015).[4]



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