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Year : 2013  |  Volume : 4  |  Issue : 1  |  Page : 48-49

Monoclonal antibodies used in rheumatologic disorders


Department of Pharmacology, Father Muller Medical College, Mangalore, Karnataka, India

Date of Web Publication20-May-2013

Correspondence Address:
Padmaja Udaykumar
Department of Pharmacology, Father Muller Medical College, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-9727.112295

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How to cite this article:
Ravichandra V, Udaykumar P. Monoclonal antibodies used in rheumatologic disorders. Muller J Med Sci Res 2013;4:48-9

How to cite this URL:
Ravichandra V, Udaykumar P. Monoclonal antibodies used in rheumatologic disorders. Muller J Med Sci Res [serial online] 2013 [cited 2020 Jun 1];4:48-9. Available from: http://www.mjmsr.net/text.asp?2013/4/1/48/112295

Advances in medical research has facilitated the identification and production of a number of proteins with potent, effects on specific component of human immune system. Biologics or biological response modifiers are genetically engineered proteins derived from human genes. Biological response modifiers have revolutionized the treatment of rheumatoid arthritis (RA) over the past decade. [1] They target cytokines and cell surface molecules involved in pathophysiology of the disease process. In RA, these drugs reduce joint inflammation, limit erosive damage, decrease disability, and improve quality of life. [2]

Recent advances in hybridoma technology of immunoglobulins (IgGs) have led to the development of humanized monoclonal antibodies (Mabs) directed against several diseases. Several of these engineered antibodies are useful in rheumatologic disorders. The nomenclature adopted for naming therapeutic Mabs is to end the name in-ximab for chimeric antibodies and umab for full humanized antibodies [Table 1]. [3]
Table 1: Tumor necrosis factor‑α inhibitors in rheumatology

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Biological response modifiers are proteins derived from the genetic engineering of living cells and are used to modify a patient's immune response. In the case of rheumatologic diseases, they are used to suppress destructive inflammatory responses by specifically targeting key mediators, such as cytokines, (e.g. tumor necrosis factor [TNF]-α) interleukins (ILs), etc. [4]

The TNF inhibitor etanercept, which was approved in 1998 for severe RA was the first biologic available for use in the rheumatologic disease. Since then, several additional biologic response modifiers have been developed. These agents when combined with standard drugs such as methotrexate (MTX) have significantly increased the treatment success in inflammatory arthropathies by reducing disease activity and radiographic progression and thereby improving disability and quality of life.

Five TNF inhibitors have been approved for treatment in rheumatologic diseases; etanercept, infliximab, adalimumab, certolizumab, and golimumab. Their indications include RA (all), psoriatic arthritis (all but certolizumab), ankylosing spondylitis (all but certolizumab), and juvenile idiopathic arthritis (JIA) (etanercept, adalimumab). All are given parenterally.

Etanercept is a human IgG-TNF receptor fusion protein, binds to circulating TNF and inactivates it when given subcutaneously. The remaining four are anti-TNF Mabs, containing varying proportions of mouse protein. Infliximab, a chimeric monoclonal antibody containing 25% mouse protein, should be used along with MTX to minimize the production of human anti-chimeric antibodies. Before the starting of therapy with a TNF inhibitor, patients should be screened for latent tuberculosis. Patients on a TNF inhibitor should be monitored for infection, heart failure. Less common side-effects include neutropenia, demyelinating disease, skin cancer, and induction of autoimmunity. Patients may be at increased risk of malignancies such as lymphoma. [5]

Abatacept: [Table 2] Abatacept blocks the co-stimulation of T cell by B cells suppressing T cell mediated cytokine release and promotes B cell activities. [6] It is indicated for RA that has been unresponsive to standard Disease Modifying Anti Rheumatoid Drugs (DMARDs). It is given by intravenous or subcutaneous injections. The major side effect of abatacept is the risk of serious infections, particularly bronchial and pulmonary.
Table 2: Other approved biological response modifiers

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Rituximab: Rituximab, a chimeric monoclonal antibody that depletes B cells is indicated for the use with MTX in RA that has not adequately responded to TNF inhibition and in granulomatosis with polyangitis.

Rituximab carries boxed warnings for potentially fatal infusion reactions and possible reactivation of tuberculosis. Patients should be monitored for hypogammaglobulinemia. Responders and partial responders can be retreated as frequently as every 24 weeks.

IL-1 β inhibitors: IL-1 β, initially thought to play a major role in RA, is a key mediator of inflammation in gout and many auto inflammatory diseases, including familial  Mediterranean fever More Details.

Anakinra: Anakinra, a once daily injectable IL-1 inhibitor, is indicated for use in RA unresponsive to standard DMARDs. It may be used alone or in combination with standard DMARDs. Injection site reactions and infections (less commonly) are potential side effects.

Tocilizumab: Tocilizumab is an intravenously administered humanized monoclonal antibody that targets IL-6. It is indicated for use in patients with RA that has been unresponsive to at least one TNF inhibitor or systemic JIA. It may be given with DMARDs or as monotherapy. Tocilizumab reduces systemic inflammatory features of fatigue, anemia of chronic disease and elevated C Reactive Protein (CRP). Side effects include infection, elevated transaminases, neutropenia, elevations in cholesterol, and triglycerides, and rarely gastrointestinal perforations. Patients should be screened for tuberculosis before administration of tocilizumab. [5]

In conclusion, many recombinant proteins/Mabs that inhibit pathogenically relevant cytokines, especially, TNF-α and IL-1 have been developed in recent times. These agents are generally added to MTX when the response to therapy is inadequate or in rapidly progressive cases. Although, side effects are few, patients should be screened for tuberculosis prior to starting with these drugs. All are very expensive.

 
  References Top

1.Edison JD, Gilliland WR. Optimizing therapeutics: The next front in the war on rheumatoid arthritis. Clin Pharmacol Ther 2012;91:561-6.  Back to cited text no. 1
    
2.Scott DL. Biologics based therapy for the treatment of rheumatoid arthritis. Clin Pharmacol Ther 2012;91:30-43.  Back to cited text no. 2
    
3.Chabner BA, Barnes J, Neal J, Olson E, Mujagic H, Sequist L, et al. Targeted Therapies: Tyrosine Kinase Inhibitors, Monoclonal antibodies, and Cytokines In: Brunton LL, editor. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12 th ed. New York: The McGraw-Hill Companies Inc.; 2012. p. 1745-8.  Back to cited text no. 3
    
4.Lake DF, Adrienne D Briggs Emmanuel T Akporiaye. Immunopharmacology. In: Katzung BG, Masters SB, Trevor AI, editors. Basic and Clinical Pharmacology. 12 th ed. New York: The McGraw-Hill Companies Inc.; 2012, p. 991-4.  Back to cited text no. 4
    
5.Miller AV, Sriya KM Ranatunga. Immunotherapies in Rheumatologic Disorders. In: Hetherington P, editor. Medical Clinics of North America: Immunotherapy in Clinical Medicines. vol 96. Philadelphia, Pennsylvania: W.B. Saunders Company, A division of Elsevier Inc; 2012. p. 475-93.  Back to cited text no. 5
    
6.Armstrong AW, Armstrong EJ, Klickstein LB. Pharmacology of Immunosuppression. In: Golon D Editor. The Pathophysiologic Basis of Drug Therapy. 3 rd ed. Philadelphia: Lippincott Williams Wilkins, A Wolters Kluwer Business; 2012. p. 800-2.  Back to cited text no. 6
    



 
 
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