Rheumatoid Arthritis: Common Questions About Diagnosis and Management

Amy Wasserman

<< Previous article

Next article >>

Apr 1, 2018 Issue

Rheumatoid Arthritis: Common Questions About Diagnosis and Management

AMY WASSERMAN, MD, Westchester Medical Center, New York Medical College, Valhalla, New York

Am Fam Physician. 2018 Apr 1;97(7):455-462.

Patient information: A handout on this topic is available at http://familydoctor.org/familydoctor/en/diseases-conditions/rheumatoid-arthritis.html.

Author disclosure: No relevant financial affiliations.

Article Sections

Abstract
What Is the Typical Presentation of RA, and How Is It Diagnosed?
What Are the Extra-Articular Manifestations of RA, and How Common Are They?
What Are the First-Line Treatments for RA?
How Do Early Intervention and Treat-to-Target Affect the Course of RA?
How Do Comorbidities Impact the Management of RA?
Can Patients with RA Taper or Discontinue Medication Use and Remain in Remission?
References

Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis, with a lifetime prevalence of up to 1% worldwide. Women, smokers, and those with a family history of the disease are most often affected. Rheumatoid arthritis should be considered if there is at least one joint with definite swelling that is not better explained by another disease. In a patient with inflammatory arthritis, the presence of a rheumatoid factor and/or anti-citrullinated protein antibody, elevated C-reactive protein level, or elevated erythrocyte sedimentation rate is consistent with a diagnosis of rheumatoid arthritis. Rheumatoid arthritis may impact organs other than the joints, including lungs, skin, and eyes. Rapid diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic drugs, which is associated with better outcomes. The goal of therapy is to initiate early medical treatment to achieve disease remission or the lowest disease activity possible. Methotrexate is typically the first-line agent for rheumatoid arthritis. Additional disease-modifying antirheumatic drugs or biologic agents should be added if disease activity persists. Comorbid conditions, including hepatitis B or C or tuberculosis infections, must be considered when choosing medical treatments. Although rheumatoid arthritis is often a chronic disease, some patients can taper and discontinue medications and remain in long-term remission.

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, with a lifetime prevalence of up to 1% worldwide.1 It has a significant impact on occupational and daily activities, as well as mortality.2–4 This article reviews common questions on the diagnosis and management of RA, and presents evidence-based answers.

WHAT IS NEW ON THIS TOPIC

The 2015 American College of Rheumatology guidelines continue to recommend methotrexate as the first-line treatment for rheumatoid arthritis, unless contraindications (e.g., frequent alcohol use, preexisting liver disease) are present.

In a randomized trial of patients who were on stable disease-modifying antirheumatic drug (DMARD) regimens and in clinical remission for at least six months, 84% of patients who continued full DMARD treatment remained in remission after 12 months, compared with 61% who tapered DMARDs by 50%, and with 48% of those who stopped all DMARDs.

Enlarge Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation	Evidence rating	References
Methotrexate should be the first-line disease-modifying antirheumatic drug in patients with rheumatoid arthritis unless there are contraindications.	A	16–18
Patients with rheumatoid arthritis should be treated as early as possible to have the best chance of remission.	A	19–25
Patients should be screened for chronic infections, including latent tuberculosis, hepatitis B virus, and hepatitis C virus, before starting rheumatoid arthritis treatment.	C	16, 27, 28
Patients who are in remission from rheumatoid arthritis for more than six months and on stable medication regimens are candidates for tapering or discontinuing disease-modifying antirheumatic drug or biologic treatment.	B	35, 36

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation	Evidence rating	References
Methotrexate should be the first-line disease-modifying antirheumatic drug in patients with rheumatoid arthritis unless there are contraindications.	A	16–18
Patients with rheumatoid arthritis should be treated as early as possible to have the best chance of remission.	A	19–25
Patients should be screened for chronic infections, including latent tuberculosis, hepatitis B virus, and hepatitis C virus, before starting rheumatoid arthritis treatment.	C	16, 27, 28
Patients who are in remission from rheumatoid arthritis for more than six months and on stable medication regimens are candidates for tapering or discontinuing disease-modifying antirheumatic drug or biologic treatment.	B	35, 36

Enlarge Print

BEST PRACTICES IN RHEUMATOLOGY

Recommendations from the Choosing Wisely Campaign

Recommendation	Sponsoring organization
Do not prescribe biologics for rheumatoid arthritis before a trial of methotrexate (or other conventional nonbiologic disease-modifying

The Author

AMY WASSERMAN, MD, is an assistant professor in the Rheumatology Department at Westchester Medical Center, New York Medical College, Valhalla, NY.

Address correspondence to Amy Wasserman, MD, Westchester Medical Center, 100 Woods Rd., Taylor Care Pavilion, 3rd Fl., Valhalla, NY 10595 (e-mail: amy.wasserman@wmchealth.org). Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR, Kelley WN. Kelley's Textbook of Rheumatology. 9th ed. Philadelphia, Pa.: Elsevier/Saunders; 2013:1059-1108....

2. Mackey RH, Kuller LH, Deane KD, et al. Rheumatoid arthritis, anti-cyclic citrullinated peptide positivity, and cardiovascular disease risk in the Women's Health Initiative. Arthritis Rheumatol. 2015;67(9):2311–2322.

3. England BR, Sayles H, Michaud K, et al. Cause-specific mortality in male US veterans with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):36–45.

4. Verstappen SM. Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and presenteeism. Best Pract Res Clin Rheumatol. 2015;29(3):495–511.

5. Wasserman AM. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2011;84(11):1245–1252.

6. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [published correction appears in Ann Rheum Dis. 2010;69(10):1892]. Ann Rheum Dis. 2010;69(9):1580–1588.

7. Combe B, Benessiano J, Berenbaum F, et al. The ESPOIR cohort: a ten-year follow-up of early arthritis in France: methodology and baseline characteristics of the 813 included patients. Joint Bone Spine. 2007;74(5):440–445.

8. Biliavska I, Stamm TA, Martinez-Avila J, et al. Application of the 2010 ACR/EULAR classification criteria in patients with very early inflammatory arthritis: analysis of sensitivity, specificity and predictive values in the SAVE study cohort. Ann Rheum Dis. 2013;72(8):1335–1341.

9. Keystone EC, Haraoui B, Guérette B, Mozaffarian N, Liu S, Kavanaugh A. Clinical, functional, and radiographic implications of time to treatment response in patients with early rheumatoid arthritis: a posthoc analysis of the PREMIER study. J Rheumatol. 2014;41(2):235–243.

10. Wallenstein GV, Kanik KS, Wilkinson B, et al. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016;34(3):430–442.

11. Turesson C, Jacobsson L, Bergström U. Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford). 1999;38(7): 668–674.

12. Gabriel SE, Crowson CS, Kremers HM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum. 2003;48(1):54–58.

13. Kim SK, Park SH, Shin IH, Choe JY. Anti-cyclic citrullinated peptide antibody, smoking, alcohol consumption, and disease duration as risk factors for extraarticular manifestations in Korean patients with rheumatoid arthritis. J Rheumatol. 2008;35(6):995–1001.

14. Richman NC, Yazdany J, Graf J, Chernitskiy V, Imboden JB. Extraarticular manifestations of rheumatoid arthritis in a multiethnic cohort of predominantly Hispanic and Asian patients. Medicine (Baltimore). 2013;92(2):92–97.

15. Turesson C, Schaid DJ, Weyand CM, et al. Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(9):2776–2783.

16. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1–25.

17. Verschueren P, De Cock D, Corluy L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015;74(1):27–34.

18. Klareskog L, van der Heijde D, de Jager JP, et al.; TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363(9410):675–681.

19. Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000;43(1):22–29.

20. Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol. 1995;22(12):2208–2213.

21. Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004;43(7):906–914.

22. van der Linden MP, le Cessie S, Raza K, et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 2010;62(12):3537–3546.

23. van Nies JA, Tsonaka R, Gaujoux-Viala C, Fautrel B, van der Helmvan Mil AH. Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts. Ann Rheum Dis. 2015;74(5):806–812.

24. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52(11):3381–3390.

25. Markusse IM, Akdemir G, Dirven L, et al. Long-term outcomes of patients with recent-onset rheumatoid arthritis after 10 years of tight controlled treatment: a randomized trial. Ann Intern Med. 2016;164(8): 523–531.

26. Souto A, Maneiro JR, Salgado E, Carmona L, Gomez-Reino JJ. Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies. Rheumatology (Oxford). 2014;53(10):1872–1885.

27. Lan JL, Chen YM, Hsieh TY, et al. Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2011;70(10):1719–1725.

28. Brunasso AM, Puntoni M, Gulia A, Massone C. Safety of anti-tumour necrosis factor agents in patients with chronic hepatitis C infection: a systematic review. Rheumatology (Oxford). 2011;50(9):1700–1711.

29. Mann DL, McMurray JJ, Packer M, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004;109(13):1594–1602.

30. Chung ES, Packer M, Lo KH, et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107(25):3133–3140.

31. Raaschou P, Simard JF, Asker Hagelberg C, Askling J; ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ. 2016;352:i262.

32. Raaschou P, Simard JF, Holmqvist M, Askling J; ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ. 2013;346:f1939.

33. Mercer LK, Lunt M, Low AL, et al.; BSRBR Control Centre Consortium. Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2015;74(6):1087–1093.

34. Silva-Fernández L, Lunt M, Kearsley-Fleet L, et al. The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology (Oxford). 2016;55(11):2033–2039.

35. Haschka J, Englbrecht M, Hueber AJ, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping anti-rheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 2016;75(1):45–51.

36. Emery P, Hammoudeh M, FitzGerald O, et al. Sustained remission with etanercept tapering in early rheumatoid arthritis. N Engl J Med. 2014;371(19):1781–1792.

Copyright © 2018 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.