Posted on 11/01/13
A 36-year-old woman initially presented to her rheumatologist with active bilateral synovitis in her hands, wrists, and ankles, and nodules on her left elbow. Her laboratory results were as follows:
- C-reactive protein (CRP) = 5.7 mg/dL (normal: 0.1–0.9 mg/dL)
- Erythrocyte sedimentation rate (ESR) = 38 mm/h (normal: 0–15 mm/h)
- Rheumatoid factor (RF) = 344 (normal: 0–29 IU/mL)
- Cyclic citrullinated peptide (CCP) = 90 (normal: 0–20)
- Other parameters within normal limits
A radiography revealed small erosions in both feet. She was subsequently diagnosed with moderate rheumatoid arthritis (RA) and started on methotrexate (MTX) at 10 mg/week, which was then increased to 15 mg/week. At her next visit, she reported some symptomatic relief after a few weeks of treatment. After 3 months, however, she visited her rheumatologist, presenting with stiffness, pain, and swelling in her wrists. Her sedimentation rate was elevated, and she complained that she could not be fully productive at work because of joint pain.
Questions to consider:
- Can this patient be considered refractory to MTX?
- How should this patient’s treatment regimen be modified?
According to Centers for Disease Control and Prevention (CDC) statistics, approximately 1.5 million US adults have RA, a chronic, autoimmune inflammatory disorder.1 The disease is characterized by synovial inflammation that causes stiffness and tenderness and can eventually lead to cartilage damage, bone erosions, and joint destruction. When inadequately treated, RA is associated with significant activity limitations and disability.2
In recent years, the primary therapeutic goals for patients with RA have shifted from relieving symptoms to reducing disease activity and progression.3 Many rheumatologists view remission as an attainable goal for their patients with RA. Regarding management strategies, research evidence and clinical experience support 2 key themes:
- Treating early and aggressively with disease-modifying antirheumatic drug (DMARD) monotherapy or combination therapy
- <span style="Times New Roman" "="">Tight control, or treating to the targets of low disease activity or remission
According to the updated 2012 guidelines of the American College of Rheumatology (ACR), patients recently diagnosed with RA (disease duration of less than 6 months) characterized by low disease activity should be treated with synthetic (nonbiologic) DMARD monotherapy.4 The standard first-line therapy is MTX (10-25 mg weekly), administered orally or subcutaneously. MTX acts by inhibiting the proinflammatory activity of autoreactive T cells, which play a key role in RA immunopathogenesis. Among other proposed mechanisms of action, methotrexate stimulates T-cell apoptosis.5 For patients with moderate disease activity and features of poor prognosis, methotrexate may be prescribed with other synthetic DMARDs, including sulfasalazine, leflunomide, or hydroxychloroquine.4
For patients recently diagnosed with moderately to severely active RA, or for patients with established RA (disease duration over 6 months) who do not respond to a synthetic DMARD, ACR guidelines recommend a tumor necrosis factor alpha (TNF-α) inhibitor, either alone or added to methotrexate.4 TNF-α inhibitors are biologic agents that bind soluble and membrane-bound TNF-α, a cytokine that causes joint inflammation and degeneration through various mechanisms. To date, 5 TNF-α inhibitors are approved by the FDA for treating moderate to severe RA: etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. Clinical trials have consistently demonstrated that, compared with methotrexate alone, the addition of a TNF-α inhibitor is associated with significantly better clinical, radiologic, and functional outcomes.6 Adverse events associated with TNF-α inhibitors include injection- or infusion-site infections, tuberculosis, and opportunistic infections. Severe adverse events include malignancies, hepatitis B and C reactivation, hematologic abnormalities, and exacerbation of congestive heart failure.7
For patients with moderate to severe disease activity who do not respond to a TNF-α inhibitor, the ACR guidelines recommend the combination of methotrexate and a biologic agent that acts through mechanisms other than blocking the effects of TNF-α.8 These biologics include:
- Rituximab, which depletes B cells and thereby inhibits their pro-inflammatory effects in RA
- Abatacept, which inhibits the activation and harmful effects of autoreactive T cells
- Tocilizumab, which blocks interleukin-6 (IL-6) signal transduction and thereby reduces the pro-inflammatory and degenerative effects of IL-6 on joint tissue
In clinical trials, patients treated with a biologic agent plus methotrexate have experienced significantly better clinical and radiologic outcomes compared with patients treated with methotrexate alone.6 Like TNF-α inhibitors, the addition of these biologics poses risks of injection- or infusion-site reactions, and patients are more susceptible to infections, especially opportunistic infections. In addition, these agents have been associated with exacerbations of chronic obstructive pulmonary disease (abatacept); rare cases of progressive multifocal leukoencephalopathy (rituximab); and elevated liver enzymes and lipids, neutropenia, and GI perforations (tocilizumab).8
As revealed through head-to-head comparison studies and meta-analyses, efficacy outcomes are generally similar for RA patients treated with different synthetic DMARDS and biologic agents, respectively.9 The Agency for Healthcare Research and Quality (AHRQ) commissioned a comprehensive analysis of new research findings, and in April 2012, published a systematic review, “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis in Adults - Update.” The review was conducted by investigators at the RTI International University of North Carolina Evidence-Based Practice Center. The comparative effectiveness review is available at no charge on AHRQ's Effective Health Care Program website (http://www.effectivehealthcare.ahrq.gov/ehc/products/203/1044/CER55_Drugtherapies-rheumatoidarthritis_FinalReport_20120419.pdf).
In conclusion, experts in rheumatology emphasize that optimal patient outcomes depend on compliance with the evidence-based and consensus therapeutic strategies of early, aggressive treatment and tight control. The ultimate patient-centered goals of therapy are to inhibit progressive structural damage, reduce comorbidity and mortality risks, restore function and quality of life, and achieve remission.4
1. Arthritis-Related Statistics. Center for Disease Control and Prevention. August 2011. www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm#1.
2. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358(9285):903-911
3. Mease PJ. Improving the routine management of rheumatoid arthritis: the value of tight control. J Rheumatol. 2010;37(8)1570-1578.
4. 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. 2012;64(5):625-639.
5. Segal R, Yaron M, Tartakovsky B. Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum. 1990;20(3):190-200.
6. McIness IB, O’Dell JR. State of the art: rheumatoid arthritis. Ann Rheum Dis. 2010;69:1898-1906.
7. Thalayasingam N, Issacs JD. Anti-TNF therapy. Best Pract Res Clin Rheumatol. 2011;25(4):549-567.
8. Agarwal SK. Biologic agents in rheumatoid arthritis: an update for managed care professionals. J Manag Care Pharm. 2011;17(9 Suppl.B):S14-18.
9. Donahue KE, Jonas DE, Hansen RA, et al. Comparative effectiveness of drug therapy for rheumatoid arthritis in adults – update. Comparative effectiveness review No. 55. Agency for Healthcare Research and Quality. AHRQ publication no.12-EHC025-EF. April 2012. http://www.effectivehealthcare.ahrq.gov/ehc/products/203/1044/CER55_Drugtherapies-rheumatoidarthritis_FinalReport_20120419.pdf.
Subscribe to RSS Feed
Life with Rheumatic Disease
The Simple Tasks campaign aims to educate rheumatology patients about policy issues impacting their care and encourage patients to advocate for healthcare policies that promote safe, effective, affordable, and accessible rheumatology care.
If you’re wondering what it’s like to live with a rheumatic disease, we invite you to explore these rheumatoid arthritis case studies and other case studies focusing on what it’s like to live with rheumatic diseases.
Lauren Lee Johnson
Lauren was 31-years old when she was officially diagnosed with lupus after 10 years of misunderstood symptoms. Two years later, Lauren received her second diagnosis of fibromyalgia. As a thriving professional, wife and mother to a beautiful 11-year-old daughter, Lauren fights to manage her symptoms each day and embrace moments of joy amid the pain. See Lauren’s Case Study >
Richard went from running 100-mile races to periodically collapsing and not being able to stand in his own home. At 37 years old, Richard was diagnosed with systemic lupus by his local rheumatologist, who – in Richard’s book – “wears a cape. He’s truly my hero.” And not only is Richard thankful for his relationship with his rheumatologist, he is grateful for the accessibility to rheumatologists within his community – an issue that many people face who live in areas where there is a deficit in the field. See Richard’s Case Study >
On the surface, Glen Massie is a 48-year-old man who is happily married with two kids. He works as a transportation planner with the local Metropolitan Planning Organization, and his “free” time is spent giving back. In big ways. From his active membership in the Marine Corps League, to his participation in a local bluegrass group, to his involvement in fundraising efforts for the Vasculitis Foundation, Glen’s thumbprint on the community is hard to miss. And he also volunteers his time as a clown, making others laugh. See Glen’s Case Study >
Two weeks before her 16th birthday Tierra was diagnosed with systemic scleroderma – a disease of which she knew nothing. Tierra researched her diagnosis and was lucky to immediately connect with a rheumatologist, providing the opportunity to ask questions and learn. Several years later Tierra has a deeper understanding of her diagnosis, thanks in large part to the relationship she’s built with her rheumatologist, whom she calls a true partner. Tierra shares her story to offer support and help other patients find their voice. See Teirra’s Case Study >
As a young, successful, fashion and beauty correspondent, Christine Schwab was shocked to hear she had rheumatoid arthritis at the age of 43. Christine was shocked at the diagnosis because she had always believed ‘arthritis’ to only strike elderly people, a perception she would later work hard to change. And, through her struggles, Christine has found her window of opportunity by working with a rheumatologist and becoming a rheumatology advocate. See Christine’s Case Study >
At the age of eight, Katie Emmerson was diagnosed with polyarticular juvenile arthritis during surgery to remove a tumor from her wrist. By the age of 12, her arthritis left her in a wheelchair. Now, at 27, Katie sees everyday tasks as major battles and triumphs. And, Katie has found her window of opportunity by encouraging others with rheumatic diseases to see a rheumatologist early. See Katie’s Case Study >
Diagnosed with both rheumatoid arthritis and lupus at 50, Michael Taffe found the simple tasks of opening medicine bottles, holding a coffee mug, and working impossible. But, he also found his window of opportunity. See Michael’s Case Study >
Maya Rogers was a normal eight-year-old child until her family noticed subtle symptoms that led to a diagnosis of juvenile arthritis. Limited access to a rheumatologist and financial and insurance restrictions forced the entire Rogers family to make tough decisions for the health of Maya. With the help of a rheumatologist and Maya’s positive attitude, the family found their window of opportunity. See the Rogers family Case Study >
As an active, vibrant 18 year old, Shanelle Gabriel’s life was changed when a series of seemingly random symptoms led to a diagnosis of lupus. While lupus has robbed Shanelle of her ability to dance competitively, she has found her window of opportunity to through appropriate treatment by a rheumatologist and by using her disease to inspire new art in her life. See Shanelle’s Case Study >
Diagnosed with juvenile idiopathic arthritis at 10, Ashley Boynes-Shuck found the simple tasks of playing softball and brushing her teeth impossible. But, she also found her window of opportunity. See Ashley’s Case Study >
She was 15-months old when she was officially diagnosed with juvenile idiopathic arthritis. Despite her everyday struggles, Alexa has a glowing spirit and a positive outlook on life, with big hopes for the future. Alexa, by many definitions, is lucky because she was diagnosed early – within the window of opportunity. See Alexa’s Case Study >
He was an active 19-year-old when he was diagnosed with gout. Like many, before his diagnosis Seth had no idea what rheumatic disease was. But he found his window of opportunity. See Seth’s Case Study >
Leslie M. was 19-years old when she was diagnosed with rheumatoid arthritis and 26-years old when she was diagnosed with undifferentiated connective tissue disease (UCTD). Now 28-years old, Leslie seeks to educate other young women on the unexpected impact of rheumatic diseases. See Leslie’s Case Study >