Journal Club

Therapeutic Uses of Infliximab

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Instructions

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Post-Test

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Objectives:

Upon completion of this course the participant will be able to:

Describe the composition of infliximab

Describe two potential mechanisms of infliximab

Name four disease states that may benefit from infliximab therapy

      List the goals of infliximab treatment in at least one disease state

Introduction:

Infliximab (marketed in the United States as Remicade® by Centocor, Inc.) is a drug approved by the FDA for treatment of Crohn's disease and Rheumatoid Arthritis.  Recent clinical trials focusing on the inflammatory diseases have shown that anti-tissue necrosis factor alpha (TNF-α) drugs can play a significant role in reducing and or alleviating the symptoms and manifestations associated with these diseases. Infliximab falls into this category and has shown its efficacy in a variety of disease states. This Journal Club examines this relatively new drug and its various uses as seen in recent clinical research.

To understand the current therapeutic uses of tumor necrosis factor alpha blocking agents, such as infliximab, in the treatment of rheumatoid arthritis, Crohn’s disease, and others, it is necessary to briefly discuss some of these disease processes.

Rheumatoid Arthritis 

Rheumatoid arthritis is a chronic, systemic inflammatory disease that primarily attacks peripheral joints and surrounding muscles, tendon, ligaments and blood vessels. Spontaneous remissions and unpredictable exacerbations can and do occur in rheumatoid arthritis (RA). Potentially crippling, RA usually requires lifelong treatment and sometimes surgery. In most patients, the disease follows an intermittent course and allows normal activity, although around 10% suffer total disability. Prognosis worsens with the development of nodules, vasculitis, and high titers of rheumatoid factor. Rheumatoid arthritis is believed to have an autoimmune basis, though the exact cause remains unknown.

Initial symptoms of RA include malaise, fatigue, anorexia, persistent low-grade fever, weight loss, and lymphadenopathy, as well as vague articular symptoms. Later symptoms include the development of joint pain, tenderness, warmth, and swelling. Joint symptoms usually occur bilaterally and symmetrically. Other symptoms include morning stiffness, parasthesias in hands and feet, and stiff, weak or painful muscles. The patient may also develop rheumatoid nodules (subcutaneous round or oval, non-tender masses) usually on pressure areas, such as elbows. Advanced signs include joint deformities and diminished joint function.

Crohn’s Disease

Crohn’s disease is an inflammatory disorder that affects any part of the GI tract (usually the terminal ileum), and can extend through all layers of the intestinal wall. It can also involve the lymph nodes and the mesentery. The exact cause of Crohn’s disease is unknown, but possible causes include allergies, immune disorders, lymphatic obstructions, infections, and genetic factors. It is most commonly found in in adults aged 20-40 years.

A wide range of symptoms may be seen. But these can vary according to their location and the extent of inflammation present, and at first may be mild and nonspecific. In acute disease, the signs and symptoms may include any of the following: right lower abdominal quadrant pain, cramping, tenderness, flatulence, nausea, fever, diarrhea, and bleeding.¹ In chronic disease, the patient usually experiences diarrhea (4-6 stools per day), right lower quadrant pain, steatorrhea, marked weight loss, and possible weakness, lack of ambition and inability to cope with stress.²