2007 ACR CME Activity - Case Study

CME Information

Accreditation Statement: The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Credit Designation: The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality and scientific integrity of this CME activity

Educational Goal: To help address the unmet needs between current knowledge and its application in patient care, the Highlights from the 71st Annual ACR Meeting: A Continuing Education Series seeks to provide rheumatologists and to other related healthcare professionals with the latest clinical information and data from the 71st Annual American College of Rheumatology Meeting.

Learning Objectives: At the conclusion of this activity, participants should be able to:

1. Discuss key data being presented at the annual ACR meeting in a manner that is practical and clinically relevant.
   
2. Assess how biologics can be incorporated into appropriate therapeutic strategies based on their different mechanisms of actions, response rates, frequency of administrations and safety and tolerability profiles.
   
3. Recognize the long-term implications of biologic therapy on joint stability and mobility, cardiovascular complications and other risk factors.
   

Release Date: November 29, 2007

Expiration Date: November 29, 2008

Estimated time for completion: 30 minutes

Target Audience: This activity is intended for rheumatologists and relatedhealthcare professionals. There are no prerequisites for participants.

Faculty and Qualifications:

• Alan Baer, MD, Associate Professor of Medicine and Director, Johns Hopkins University Clinical Practice at Good Samaritan Hospital, Chief of Rheumatology at Good Samaritan Hospital
  
• Jon T. Giles, MD, Assistant Professor of Medicine, Division of Rheumatology, Department of Medicine, Johns Hopkins University
  
• Vicky Ruffing, RN, Nurse Manager, Johns Hopkins Arthritis Center
  

Disclosure Statements: As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed of any commercial product(s) discussed in an educational presentation. The presenting faculty reported the following:

• Alan Baer, MD - Dr. Baer has no financial relationships to disclose.
  
• Jon T. Giles, MD – Dr. Giles discloses the following: Grants/Research Support: Roche, Centocor; Consultant: Abbott Laboratories; Honorarium: Prous Science, Amgen.
  
• Vicky Ruffing, RN – Ms. Ruffing discloses the following:Consultant for Roche, Amgen, Genentech, BMS, and Abbott

Off-Label Statement: No faculty member has indicated that their presentation will include information on off-label products.

Disclaimer: The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contradictions, warnings and adverse effects before administering pharmacologic therapy to patients.
Method of Participation: In order to receive your certificate follow the link to the post-test, achieve a score of at least 70 percent and complete the program evaluation. Upon successful completion follow the directions to print your certificate.This activity is designed to be completed within the time designated; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period.

She reports smoking in high school and college but stopped 15 years ago. She consumes about 2 alcoholic drinks per day on weekends.

Introduction

This educational case study highlights information from several key abstracts presented at the 71st annual meeting of the American College of Rheumatology (ACR) held November 6-11, 2007, in Boston, Massachusetts. It is important to note that treatment for rheumatoid arthritis should be evidence-based and must be tailored to the needs of the individual patient. This case study is not meant to endorse any particular products but rather to measure your ability to retain the information presented in previous activities.

Case Study

SJ is a 48-year-old woman who presents for her first follow-up visit with her rheumatologist following a diagnosis of rheumatoid arthritis (RA). She states, “I still wake up feeling stiff and some days I can’t seem to get going at all.” She reports losing 10 pounds over the previous 3 months.

SJ was diagnosed with seropositive RA 4 months ago, although her joint symptoms began 8 months ago. She had a hysterectomy for dysfunctional uterine bleeding 7 years earlier. She has no other significant medical history.

Her family history is significant because of diabetes in her mother and hypertension and coronary artery disease in her father. Both are still living with no history of RA.

SJ lives with her husband and 2 children ages 12 and 8. Her husband is an electrical contractor and SJ manages the scheduling and billing for the business.

SJ was started on prednisone 5 mg QD and methotrexate (MTX) 10 mg once q week when RA diagnosis was confirmed 4 months ago. The dose of MTX was increased to 15 mg once q week at her last visit 3 months ago.

She also takes over-the-counter ibuprofen 800 mg TID, folic acid 1 mg PO QD, calcium carbonate 1200 mg QD, and vitamin D 400 IU QD.

Pertinent physical exam findings:

• Mild to moderate swelling and tenderness in: the wrists, the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of all fingers in both hands, the metatarsophalangeal (MTP) joints in both feet, and both knees
  
• Rheumatoid nodules noted on hands and right forearm
  
• Cardiovascular: WNL
  
• Pulmonary: WNL
  
• Liver: liver edge not palpable

Pertinent laboratory results and tests (normal range):

• Hg: 11 g/dL (12-15 g/dL)
  
• BUN: 12 mg/dL (5-20 mg/dL)
  
• serum Cr: 0.8 mg/dL (0.4-1.2 mg/dL)
  
• glucose (postprandial): 148 mg/dL (up to 140 mg/dL)
  
• AST: 25 IU/L (20-48 IU/L)
  
• ALT: 21 IU/L (< 35 IU/L)
  
• CRP: 1.0 mg/dL (<0.3 mg/dL)
  
• ESR: 38 mm/hr (5-15 mm)
  
• ANA: negative
  
• CCP antibody test: positive (80 units)
  
• Hepatitis B and C serology: negative
  

Radiographs of her hands show soft tissue swelling of the MCP and PIP joints bilaterally, early erosions at the MCP joints, and periarticular osteopenia. Her disease activity score (DAS28) is 5.1 at this visit. And a T-score based on dual-energy x-ray absorptiometry (DXA) of the spine is -1.8.

Follow the link at the conclusion of this Case Study to post your answer.

1. What are the goals of therapy for patients with RA?

A. Improve functional capacity
B. Achieve disease remission
C. Effectively manage underlying emotional and social issues
D. A and B
E. B and C
F. A, B, and C

The primary goal for patients with RA is to improve or maintain functional capacity and improve quality of life on physical, social, and emotional levels. (1) Individual successes that help attain this are controlling disease activity, controlling pain and discomfort, minimizing disease progression, preventing or correcting deformities, and effectively treating disease-related complications. It is also critical to evaluate for and treat underlying emotional and social issues such as depression. Allied healthcare interventions could include education on RA, medication adherence, time management, and nonpharmacologic pain management. Of course the ultimate goal in treating RA is to achieve complete disease remission while avoiding serious adverse effects associated with therapy. (1)

Disease remission can be measured using the ACR or DAS28 criteria.2-5 In a recent presentation at the ACR annual meeting, Dr. Paul Emery noted, “Clinical remission, as measured by DAS28, is an important goal in clinical practice, and is perhaps the most relevant to patients’ daily lives as they struggle with their symptoms.” (6)

Using objective measures of patient outcomes does improve the control of RA.2,7,8 For example, the Tight Control of RA (TICORA) Trial proved the effectiveness of treatment decisions based on routine clinical disease activity measures. (2,7) In this study, adjusting therapy by monitoring disease activity scores at each visit and making protocol-defined changes resulted in better outcomes compared to routine care. This study also showed that tight disease control substantially improves disease activity, radiographic progression, and quality of life. (2,7) It is also important to note that patients with RA have a reduced life expectancy, mainly due to co-morbid conditions such as cardiovascular disease. Therefore, it is important to manage risk factors and prescribe appropriate preventive treatments. (9)

The primary goal for patients with RA is to improve or maintain functional capacity and improve quality of life on physical, social, and emotional levels.

Follow the link at the conclusion of this Case Study to post your answer.

2. What changes in medications should be made at this time?

A. Increase the MTX dose to 20 mg PO q week
B. Add a TNF-inhibitor
C. Add hydroxychloroquine and/or sulfasalazine
D. Add leflunomide
E. All of the above are reasonable

Decisions in clinical practice must be made based on the best available current evidence to minimize or eliminate disease activity while weighing the risks of more potent or combination therapy. Patient and clinician satisfaction with the current therapy are also important considerations. (1,2)

MTX is generally considered the first-line disease-modifying drug (DMARD) of choice for RA to which the newer biologic drugs are added. One possible advantage of MTX over other DMARDs is that users demonstrate a decrease in mortality compared to nonusers, including a significant reduction in cardiovascular mortality.1,10 Because the effects of MTX are dose-related, it may be reasonable to increase SJ’s dose to 20 mg/week and evaluate response in 6 to 8 weeks. In clinical practice, serious toxicities are infrequent with appropriate monitoring. (1) It is important to take enough time for appropriate evaluation of the efficacy of the increased dose of MTX before adding additional agents. However, if she does not respond to the higher dose of MTX, adding any of the other agents listed above is a reasonable option.

One current school of thought for patients such as SJ (with signs of severe RA, active disease based on DAS28 scores, and nonresponsders to MTX) is to implement combination therapy with oral DMARDs or add biologic therapy to MTX. In general, evidence of early joint destruction and the associated poor outcomes have led to increased emphasis on starting more aggressive treatments early. There is strong evidence from clinical trials that “more aggressive treatment with combination therapy in early RA results in superior clinical outcomes, functional status, reduced work disability, and sustained disease remission when compared with monotherapy.”1 For biologics, most combinations that have been studied include MTX and there is evidence from clinical trials to support the combination of MTX plus etanercept, infliximab, or adalimumab.1 The COMET trial, a multicenter, randomized, double-blind trial of etanercept plus MTX (n = 274) versus MTX alone (n = 268) in patients with active early RA showed that a higher proportion of patients treated with the combination achieved the primary endpoint of remission (DAS < 2.6) at week 52, 50% versus 18% (P < .001). At baseline, the mean disease duration was 7 months, DAS28 was 6.5, and 22% of patients had prior DMARD use. The proportion of patients achieving DAS remission was significantly greater in the combination therapy group by week 2 and at all timepoints thereafter. (11)

Follow the link at the conclusion of this Case Study to post your answer.

3. The use of anti-TNF agents may decrease SJ’s risk for myocardial infarction (MI).

A. True
B. False

The risk of MI is increased in patients with RA. A recent longitudinal databank study presented at the ACR annual meeting that evaluated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-TNF therapy on the risk of MI in 22,818 incident cases of MI between 1998 and 2006 (including 17,712 patients with RA and 5081 with noninflammatory rheumatic disorders [NIRD]) showed:

• MI was increased in RA compared with NIRD: relative risk (RR) 1.6 (95% CI 1.1-2.1).
  
• MI risk was strongly associated with baseline Health Assessment Questionnaire (HAQ) score, prednisone use, hypertension, diabetes, previous MI, and lifetime smoking exposure.
  
• Anti-TNF therapy was used by 56.2% of RA patients (adalimumab 9.0%, etanercept 33.6%, infliximab 40.3%) and all anti-TNF agents were associated with a reduced risk of MI RR 0.7 (0.5-0.9) after adjusting for baseline HAQ, prednisone use, hypertension, diabetes, and lifetime smoking exposure.
  
• An increased adjusted RR (1.3) of MI was seen in patients treated with prednisone. (12)
  

Follow the link at the conclusion of this Case Study to post your answer.

4. How should SJ’s osteopenia be managed?

A. Add a bisphosphonate
B. Taper the prednisone as soon as RA activity is better controlled
C. Begin hormone replacement therapy
D. A or B
E. B or C
F. A, B, or C

Bisphosphonates are currently the standard of care for osteoporosis prevention and treatment in patients with RA. Major barriers to effective outcomes with bisphosphonates include gastrointestinal side effects, poor gastrointestinal absorption, and typically low adherence to therapy, emphasizing a clinical place for nonoral options. Although not in widespread use, anabolic agents may prove to be a useful adjunct to bisphosphonates in specific patients at high risk for fracture. At the recent ACR annual meeting, results of 2 studies showed that:

• Teriparatide, an anabolic bone-building agent, administered as an SC injection of 20 μg QD was shown to result in greater increases in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck although both treatments were effective. The study population included 428 patients (81% women) with RA on a dose equivalent of prednisone ≥ 5 mg QD for at least 3 months and either low BMD or antecedent fractures (49%). Baseline lumbar spine BMD was 0.85 (0.13) g/cm2 and T-score was -2.5 (1.0). In addition, fewer new vertebral fractures occurred with teriparatide (1/171, 0.6%) than with alendronate (10/165, 6.1%) (P = .004), but the incidence of nonvertebral fractures was not significantly different (8/214, 3.7%, and 12/214, 5.6%, respectively). (13)
  
• The HORIZON-RFT showed that zoledronic acid (ZOL) 5 mg IV once a year (n = 1054) versus placebo (n = 1057) in 2111 men and women ≥ 50 years of age with previous hip fracture (42% with a T-score less than -2.5) decreased the following:
  
  • 2-year cumulative event rate by 35% (8.59% versus 13.88%, HR = 0.65, 95% CI: 0.50-0.84; P = .0012)
    
  • Risk for clinical vertebral fractures by 46% (HR = 0.54, 95% CI: 0.32-0.92; P = .0210); nonvertebral fractures by 27% (HR = 0.73; 95% CI: 0.55-0.98; P = .0338); and hip fractures by 30% (HR = 0.70, 95% CI: 0.411-1.19; P = .1815, NS)
    
  • Total mortality by 28% (9.58% versus 13.24%, HR = 0.82; 95% CI: 0.56-0.93, P = .0117)14
    

Follow the link at the conclusion of this Case Study to post your answer.

5. What newer treatment options may soon be available to SJ based on the latest evidence from clinical trials?

A. Certolizumab pegol
B. Ocrelizumab
C. Toclizumab
D. A and B
E. A and C
F. A, B, and C

Certolizumab pegol (CZP) is the first PEGylated, Fc-free low molecular weight anti-TNF antibody to be studied in RA. It has shown good efficacy and tolerability as add-on therapy to MTX in patients refractory to MTX monotherapy in 2 phase III clinical trials: RAPID 1 and RAPID 2. It is designed to have a long half-life (14 days) and selectively target TNF-α with high affinity. (15,16)

Ocrelizumab is a humanized monoclonal antibody directed at the CD20 site on B-cells. A recent phase I/II study in patients with moderate to severe RA who were rheumatoid factor positive (RF+) with inadequate response to at least MTX showed good efficacy based on ACR20, -50, and -70 and moderate/good EULAR scores and good tolerability. (17)

The OPTION Study evaluated the efficacy and safety of tocilizumab (TCZ), a novel humanized antihuman IL-6 receptor antibody, in patients with moderate to severe active RA despite treatment with MTX. This phase III study showed excellent efficacy based on ACR20, ACR50, ACR70 and DAS28, and TCZ was well tolerated with a slightly increased risk for serious infections. (18)

Outcomes / Posttest

• Posttest and Evaluation for this Activity

References

1. Knell ME. Rheumatology: osteoarthritis and rheumatoid arthritis. Pharmacotherapy Self-Assessment Program. Fifth ed. Lenexa, KS: American College of Clinical Pharmacy; 2007.
2. Narla H, Latinis K. Features: case studies in treating rheumatoid arthritis. http://www.arthritispractitioner.com/article/7685. Published . Accessed November 2007.
   
3. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 1993;36(6):729-740.
   
4. Van der Heijde DM, van ‘t Hof MA, van Riel PL, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis.1990;49(11):916-920.
   
5. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-48.
   
6. Half of patients with active early rheumatoid arthritis achieved clinical remission. http://www.eurekalert.org/pub_releases/2007-11/pn-hop110707.php. Accessed November 2007.
   
7. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263-269.
   
8. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007;146(6):406-415.
   
9. Blom M, van Riel PL. Management of established rheumatoid arthritis with an emphasis on pharmacotherapy. Best Pract Res Clin Rheumatol. 2007;21(1):43-57.
   
10. Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet. 2002;359(9313):1173-1177.
    
11. Emery P, Breedveld F, Hall S, et al. Remission rates in subjects with active early rheumatoid arthritis—1 year results of the COMET trial: combination of methotrexate and etanercept in active early rheumatoid arthritis [platform presentation L17]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 10, 2007; Boston, MA..
    
12. Wolfe F, Michaud K. The effect of rheumatic disease treatment on the risk of myocardial infarction: increased risk from rofecoxib, valdecoxib and celecoxib; decreased risk from anti-TNF therapy [platform presentation 1340]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 9, 2007; Boston, MA.
    
13. Saag KG, Shane E, Boonen S, et al. Active-comparator trial of teriparatide versus alendronate in the treatment of glucocorticoid-induced osteoporosis [platform presentation 665]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 8, 2007; Boston, MA.
    
14. Lyles K, Colon-Emeric C, Magaziner J, et al. Efficacy and safety of zoldronic acid 5 mg in preventing fractures in men and women with prevalent hip fracture: the HORIZION-Recurrent Fracture Trial [platform presentation 666]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 8, 2007; Boston, MA.
    
15. Keystone E, Mason D, Combe B. The anti-TNF certolizumab pegol in combination with methotrexate is significantly more effective than methotrexate alone in the treatment of patients with active rheumatoid arthritis: 1-year results from the RAPID 1 Study [platform presentation 700]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 8, 2007; Boston, MA.
    
16. Landewé RB, Strand V, Smolen J, van der Heijde D. Liquid formulation certolizumab pegol with methotrexated progression of structural joint damage in rheumatoid arthritis patients: The RAPID 2 Study [platform presentation 696]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 8, 2007; Boston, MA.
    
17. Genovese M, Kaine J, Lowenstein M, et al. Ocrelizumab, a novel humanized anti-CD20 antibody: Week 72 results from a phase I/II clinical trial in patients with rheumatoid arthritis [platform presentation 695]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 8, 2007; Boston, MA.
    
18. Beaulieu AD, Rubbert-Roth A, Woodworth T, et al. Targeted inhibition of the IL-6 receptor with tocilizumab effectively reduces disease activity in patients with rheumatoid arthritis [platform presentation 2089]. Paper presented at: The Annual Meeting of the ACR/ARHP; November 10, 2007; Boston, MA.

All information contained within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.