Pharmacological Management of Rheumatoid Arthritis

PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS

OVERVIEW Rheumatoid arthritis (RA) is a chronic, autoimmune disease marked by systemic inflammation of both articular (i.e. joints) and extra-articular areas (e.g. cardiopulmonary systems). RA is a progressive disease; its onset can occur at any age but peaks around 30 to 60 years old. Females are three times as likely to be diagnosed with RA compared to males, and children can also be affected, as seen in juvenile idiopathic arthritis.[1] In total, about 1-2% of people in the United States have RA, with 80% of them testing positive for rheumatoid factors: autoantibodies produced by the immune system that are responsible for the autoimmune component of the disease.[2][3] Physical therapy plays a large role in the management of RA and physical therapists (PT) should be aware of the pathophysiology of the disease and the implications of therapeutic interventions used to delay or arrest the progression to provide proper patient care.

MECHANISM OF ACTION RA is marked by periods of exacerbation and remission. During the exacerbation period, it is theorized that certain cells, such as cytokines and tumor-necrosis-factor-alpha (TNF-⍺), cause the inflammatory and destructive process that occurs in the disease. In joint capsules, these inflammatory factors are found in the pannus, an abnormal layer of granulation tissue, and prevents the synovium from providing the necessary nutrients and lubrication to the joint. As the pannus proliferates, the space within the joint diminishes, consequently leading to the disintegration of the collagen, cartilage, and other surrounding tissues found here. Synovial hyperplasia occurs, causing local swelling and joint pain.[1] These synovial changes result in irreversible bone and joint deformity, instability, and fusion, which will further affect proper functioning of the body.[4] Extra-articular systems are similarly affected due to the inflammatory components coursing through the circulation.[1]

SIGNS AND SYMPTOMS RA begins insidiously; it starts with cartilage degradation, then moves to ligamentous laxity, followed by synovial expansion and erosion. The joints of the hand are affected early on but any joint can be affected, including the knee and temporomandibular joint. Morning stiffness is an iconic symptom of RA, along with fatigue, diffuse musculoskeletal pain, and even depression.[1] As the disease progresses, joint deformities and subluxation can occur, particularly in the cervical spine (Kim, 2005).[5] Extra-articular signs include vasculitis, anemia, myelopathy, nodulosis, scleritis, and many others.[6]

TYPES OF DRUG THERAPY There are two primary sub classifications of drugs used in the treatment of RA; drugs that provide disease modifying therapy (DMARDs) and drugs for symptomatic treatment. DMARDs are medications taken regularly for longer periods of time independent of acute symptoms. DMARDs consist of Traditional DMARDs (DMARDs) and Biological DMARDs (bDMARDs). Symptomatic therapy is used to relieve acute pain and inflammation associated with the disease process. Non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and corticosteroids are the primary drugs of choice for symptomatic therapy.[7]

DRUG CLASSES

DMARDs

bDMARDs

Corticosteroids

NSAIDs

SUMMARY

Rheumatoid Arthritis is a complex and ever-changing disease with treatment options that are just as intricate. Treatment regimen is based on disease severity, location of injury, comorbidities or contraindications, cost of drug, and the need for monotherapy or a combination of drugs.[8] Recently, there have been incredible expansions in the management of RA due to an increasing number of available drug options. The PT must be aware of the effects of each drug category in order to monitor for injurious signs and symptoms the patient may present.

NSAIDs and corticosteroids are recommended for use in the initial stages of RA for short-term and symptomatic pain relief. There are minimal side effects of NSAIDs, but signs and symptoms that may present include GI bleeding, cardiovascular issues, and dizziness.[9][10][11] Corticosteroids are also used in the initial stage as a means of reducing disease activity in patients who are awaiting a response to DMARD therapy.[12] Typical adverse effects of Corticosteroids include immunosuppression, which oftentimes leads to infection, the development of osteoporosis, and other metabolic conditions.[13] DMARDs and bDMARDs are similar in that they can adversely affect the GI system, pulmonary function, blood pressure, and cause skin irritation.[12]

Although these effects may be seemingly minor in comparison to more malignant conditions, the PT should monitor and report these symptoms as appropriate. Many of these medications may cause the patient to become frail in stature, so the PT must exercise caution during the therapy session. In addition, patient education is a significant component of care and the clinician is responsible for providing relevant treatment while remaining within the physical therapy scope of practice.

REFERENCES

  1. 1.0 1.1 1.2 1.3 Goodman CC, Fuller KS. Rheumatoid Arthritis. In: Pathology: Implications for the Physical Therapist. 4th ed. St. Louis, MO: Elsevier; 2015:1317-1328.
  2. Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ. Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis & Rheumatology. 2002;46(4):906-912. doi:0.1002/art.10167.
  3. Harris ED. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med. 1990;322(18):1277-1289.
  4. Elliot JM, Grainger AJ, Grigorian MA, Szechinksi JW, Harry KG. Rheumatoid arthritis: a guide to imaging studies. J Muscoskel Med. 1999;16(9):507-514.
  5. Kim DH. Rheumatoid arthritis in the cervical spine. J Am Acad Orthop Surg. 2005;13(7):463-474.
  6. Davis JM, Matteson EL. My treatment approach to rheumatoid arthritis. Mayo Clinic Proceedings. 2012;87(7):659-673.
  7. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1-25. doi:10.1002/acr.22783.
  8. Benjamin O, Lappin SL. Disease Modifying Anti-Rheumatic Drugs (DMARD) [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507863/
  9. U.S. Food and Drug Administration. Motrin® Ibuprofen Tablets, USP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  10. U.S. Food and Drug Administration. Voltaren® (diclofenac sodium enteric-coated tablets). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019201s046lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  11. U.S. Food and Drug Administration. Celebrex® celecoxib capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  12. 12.0 12.1 Kumar P, Banik S. Pharmacotherapy options in rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:35-43. doi:10.4137/CMAMD.S5558
  13. Bingham, C. John Hopkins University. Rheumatoid arthritis treatment. https://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/. Accessed October 3, 2018.