BDMARDs in the Management of Rheumatoid Arthritis

Overview

bDMARDs are drugs that delay the progression of RA by affecting the body’s biological response to various cytokines, particularly TNF-a. TNF-a is the primary cytokine responsible for the systemic inflammation iconic in RA and has been found at increased levels in patients with this pathology.[1] Due to this, bDMARDs can be subcategorized as either anti-TNF biologics or non-TNF biologics.[2]

Anti-TNF Biologics

PHARMACOKINETICS Anti-TNF biologics account for a substantial number of bDMARDS and work by inhibiting TNF-⍺.[3] Anti-TNF-⍺ drugs act as antagonists by attaching to TNF thus preventing it from binding its own receptor.[4] Among the most commonly used anti-TNF drugs are adalimumab, etanercept, infliximab, certolizumab pegol, and golimumab.[3] Administration of these agents is subcutaneous and results in 60-80% of bioavailability with a half-life ranging from four days (etanercept) to two weeks (certolizumab pegol and golimumab). Unfortunately, the mechanism by which these drugs are metabolized and excreted is unknown.[5][6][7][8][9]

ADVERSE EFFECTS Adverse effects are relatively mild and relate primarily to the drug’s effect on the immune system. This can cause signs and symptoms such as neutropenia, thrombocytopenia, and increased risk of infections.[10] Patients may be at risk for more serious side effects such as malignancies and cardiac adverse events if using etanercept or infliximab.[6][7]

Non-TNF Biologics

PHARMACOKINETICS In addition to anti-TNF agents, non-TNF bDMARDS work by interfering with the cell cycle, inflammatory factors, and surface proteins of lymphocyte.[10] The most common drugs include abatacept, rituximab, and tocilizumab.[3] Administration of these biologics occurs via IV and results in complete bioavailability with a half-life ranging from two days (tocilizumab) to two weeks (abatacept). Like the anti-TNF agents, the metabolism and excretion for these drugs is unknown.[11][12][13]

ADVERSE EFFECTS Adverse effects vary in severity for each non-TNF agent. Adverse effects of abatacept and tocilizumab are relatively mild, including headaches and dizziness.[11][12] However, patients taking tocilizumab have an increased risk of infection that can result in tuberculosis and opportunistic infections.[12] Rituximab can have more severe side effects such as respiratory dysfunction (bronchospasm and dyspnea), blood disorders (anemia, neutropenia, thrombocytopenia), and endocrine system imbalances (hyperglycemia, hypocalcemia).[13]

Clinical Implications

Overall, bDMARDs have fewer adverse effects than traditional DMARDS which makes them beneficial for older patients with a more complex disease.[14] However, PTs should be aware of the effects bDMARDs have on integumentary, cardiac, and immune systems. For instance, subcutaneous and intravenous injections can cause skin irritation, rash, and swelling; this should be monitored and reported to physician. Bruising, nose bleeds, or bleeding gums are signs of impaired clotting ability and should also be reported. In addition, blood pressure should be monitored at rest and during exercise to assess risk of hypertension.[5][6][7][8][9][11][12][13] Furthermore, signs such as fever, sore throat, and coughing should be monitored due to the patient’s decreased immune system and susceptibility to infection.[10]

Patients should be encouraged to report any side effects. In addition, efforts should be made to prevent infection such as washing hands and avoiding sick individuals.

References

  1. Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010;20(2):87-103.
  2. Curtis JR, Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther. 2011;33(6):679-707.
  3. 3.0 3.1 3.2 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 (Hoboken). 2012;64(5):625-39.
  4. Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): In vitro comparison with other anti-tumor necrosis factor α agents. Inflammatory Bowel Diseases. 2007;13(11):1323-1332. doi:10.1002/ibd.20225.
  5. 5.0 5.1 U.S. Food and Drug Administration. HUMIRA (adalimumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125057s409lbl.pdf. Last Modified October 16, 2018. Accessed November 24, 2018.
  6. 6.0 6.1 6.2 U.S. Food and Drug Administration. REMICADE® (infliximab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/103772s5385lbl.pdf. Last Modified June 19, 2018. Accessed November 24, 2018.
  7. 7.0 7.1 7.2 U.S. Food and Drug Administration. ENBREL® (etanercept). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/103795s5569lbl.pdf. Last Modified October 3, 2018. Accessed November 24, 2018.
  8. 8.0 8.1 U.S. Food and Drug Administration. CIMZIA® (certolizumab pegol). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125160s283lbl.pdf. Last Modified May 25, 2018. Accessed November 24, 2018.
  9. 9.0 9.1 U.S. Food and Drug Administration. SIMPONI® (golimumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125289s139lbl.pdf. Last Modified March 6, 2018. Accessed November 24, 2018.
  10. 10.0 10.1 10.2 Kumar P, Banik S. Pharmacotherapy options in rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:35-43. Published 2013 Aug 8. doi:10.4137/CMAMD.S5558
  11. 11.0 11.1 11.2 U.S. Food and Drug Administration. ORENCIA® (abatacept). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125118s209lbl.pdf. Last Modified June 30, 2017. Accessed November 24, 2018.
  12. 12.0 12.1 12.2 12.3 U.S. Food and Drug Administration. ACTEMRA (tocilizumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125276s118,125472s029lbl.pdf. Last Modified November 19, 2018. Accessed November 24, 2018.
  13. 13.0 13.1 13.2 U.S. Food and Drug Administration. RITUXAN® (rituximab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/103705s5451lbl.pdf. Last Modified October 18, 2018. Accessed November 24, 2018.
  14. Gabay C, Riek M, Scherer A, & Finckh A. Effectiveness of biologic DMARDs in monotherapy versus in combination with synthetic DMARDs in rheumatoid arthritis: Data from the Swiss Clinical Quality Management Registry. Rheumatology. 2015;54(9):1664-1672.
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